MY FRIEND .......Today at 4.20 pm Boris passed away.

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Today at 4.20 pm Boris passed away.

I received an email from his daughter, Alina, yesterday. `Just a great guy. He would help me. Cutting my food. He would tie my shoes for me, etc.... BORIS, WOULD JUST DO IT, LIKE IT WAS IN HIS DNA. A RARE FIND IN A PERSON.........BORIS YOU WILL BE MISSED.

His passing is the harsh reality of this evil challenge.

California Stem Cell and Biofocus DPI to Collaborate in ALS Association-Funded Research Using Human Motor Neurons

California Stem Cell and Biofocus DPI to Collaborate in ALS Association-Funded Research Using Human Motor Neurons
Through its TREAT ALS™ drug discovery and clinical trials program, The ALS Association announces that California Stem Cell (CSC) has signed a contract to supply international drug discovery organization BioFocus DPI, the service division of Galapagos, with its MOTORPLATE™ 96 assay-ready well plates, containing motor neuron progenitors derived from human embryonic stem cells. BioFocus DPI will use the high purity, clinical grade human motor neurons to perform assay development and screening for amyotrophic lateral sclerosis (ALS or “Lou Gehrig’s Disease”).
The Association’s TREAT ALS (Translational Research Advancing Therapy for ALS) program is funding this collaborative research project as part of its global initiative to speed the discovery of new drugs and therapies for ALS.
“The ALS Association is focused on accelerating new and promising developments from the laboratory bench into treatments for ALS,” said Lucie Bruijn, Ph.D., science director and vice president of The Association. “The unique ability of CSC to generate human motor neurons on a large scale, and the target discovery engine provided by BioFocus DPI, will contribute to the development of medicines that may significantly slow the progression of this disease and ultimately lead to a cure.” “BioFocus DPI chose to source human motor neurons from CSC because its multi-well plate format enables us to develop specialized high-throughput assays not previously possible,” said Katherine Hilyard, PhD, vice president of biological sciences, BioFocus DPI. “This the first source of high purity human motor neurons available for use in high-content screening assays. This significant advancement allows us to develop innovative human cell-based assays for the discovery of drugs for ALS and other neurological disorders.”
“CSC is delighted to help our lead customer BioFocus DPI to accelerate its drug discovery programs, and to begin to supply the marketplace with stem cell derived human motor neurons, produced using state of the art, proprietary and commercially scalable manufacturing processes. The potential market for this product in high-throughput and high-content screening analyses for predictive toxicology and drug discovery is very significant,” said Dr. Chris Airriess, CSC chief operating officer. “More importantly, CSC is proud to work toward the common mission of developing a treatment for ALS.”
BioFocus DPI aims to expand its partners’ drug pipelines by accelerating the gene-to-candidate discovery process. This is achieved through a comprehensive discovery platform, which includes target discovery in human primary cells, focused as well as diverse compound libraries, in vitro and cell-based screening, medicinal chemistry and ADME/PK services, supported by unique chemogenomic and informatics tools. As the service division of Galapagos, BioFocus DPI has over 300 employees in five countries worldwide.
California Stem Cell, Inc. is a privately held company focused on the manufacturing of high-purity human cells for therapeutic development and clinical application. Since its founding in 2005, CSC has developed and has intellectual property surrounding methods for scalable production of human motor neurons, neuronal progenitors, cardiac muscle and sino-atrial node cells at its Irvine, Calif. facility. CSC is currently in the pre-clinical development stage of stem cell based therapies for amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s Disease), spinal muscular atrophy (SMA), spinal cord injury (SCI) and coronary heart disease.
The ALS Association is a leader in ALS research and the only national not-for-profit voluntary health organization dedicated solely to the fight against ALS. The mission of The ALS Association is to lead the fight to cure and treat ALS through global cutting-edge research, and to empower people with Lou Gehrig’s Disease and their families to live fuller lives by providing them with compassionate care and support.

I'M............................

"LIFE BREAKS ALL OF US, BUT SOME OF US GET STRONGER IN THE BROKEN PLACES"

The Ependyma As A Major Player in the Pathogenesis of Amyotrophic Lateral Sclerosis: A Hypothesis

The Ependyma As A Major Player in the Pathogenesis of Amyotrophic Lateral Sclerosis: A Hypothesis
By
Anthony G. Payne, Ph.D.

Amyotrophic lateral sclerosis (ALS) is an insidious, mercilessly devastating disorder in which motor neurons that control voluntary movement are progressively lost while those that are involved in cognition and sensation are spared. At this time ALS sufferers have no scientifically validated treatment options available to them. Fifty percent succumb within three years of symptom onset and between eighty and ninety percent within five years.

At this point-in-time ALS has a complex, incompletely understood etiology. Approximately 5- 10% of cases have a genetic basis (familial ALS or fALS), with the remainder having no clearly discernible cause. The best that can be said is that ALS is very likely a multifactorial disorder triggered by any number of exposures such as environmental toxicants, either alone or in combination with specific genetic factors). This is underscored by the fact that an approximately two-fold increase in the risk of developing ALS appeared among military personnel deployed to Southwest Asia during the Gulf War (Aug 1990-July 1991) compared to non-deployed personnel.

Once the ALS disease process is underway, there are a number of pathogenic mechanisms that are felt to bring about the cellular dysfunction and apoptosis in motor neurons that are characteristic of the disease:

(1) Mitochondrial dysfunction involving, in part, oxidative stress.
(2) Excitotoxicity due, in part, to a down regulation of motor neuron glutamate transporters.
(3) A loss of calcium homeostasis in motor neurons.
(4) Disrupted protein synthesis and processing.
(5) Altered neuronal cytoskeletal function and axonal transport.
(6) Dysfunction of astrocytes and glial cells that support the CNS in general, as well as motot neurons.


Current therapeutic intervention is aimed at modulating the various pathogenic processes. Research is ongoing and involves such things as use of intravenous (IV) Ceftriaxone to upregulate glutamate transporter genes and protein expression in motor neurons.

Hypothesis

It is proposed by the author that at least some cases of ALS arise due to defective specialized neuroglial cells called ependymal cells, especially modified ependymal cells called choroidal cells that are involved in the synthesis and circulation of cerebrospinal fluid and maintenance of the blood-CSF barrier. These cells may arise, at least in part, as the end result of deleterious mutations or possibly epigenetic influences. As a result of these cellular defects in the choroidal cells, cerebrospinal fluid is synthesized that is laden with compounds that are neurotoxic, especially with respect to motor neurons, as well as rich in inflammatory cytokines and such. It is the circulation of this aberrant CSF that brings some (and in some instances perhaps all) of the pathogenic features that characterize some cases of ALS.

Support for this hypothesis comes from two sources:

(1) Direct: Published studies that show that CSF taken from ALS patients induces neurodegeneration characteristic of ALS in lab animals.
(2) Indirect: Seeming retardation in disease progression in four (4) ALS patients who have been following a regimen that modulates neurodegenerative processes shown to result when CSF from ALS patients is administered to lab animals and used in cell cultures.


Hypothesis Support - Studies

A. In a lab study conducted in India , motor neurons and spinal cord neurons in culture were exposed to CSF from 20 ALS patients and 20 controls. The “Exposure of cells to ALS-CSF drastically decreased the survival rate of motor neurons to 32.26+/-2.06% whereas a moderate decrease was observed in case of other spinal neurons (67.90+/-2.04%). In cultures treated with disease control CSF, a small decrease was observed in the survival rate with 80.14+/-2.00% and 90.07+/-1.37% survival of motor neuron and other spinal neurons respectively.” The die-off of spinal cord cells exposed to CSF from ALS patients was linked to elevation of intracellular calcium, while that of motor neurons to “activation of glutamate receptors, the AMPA/kainate receptor playing the major role.”Sen I, Nalini A, Joshi NB, Joshi PG.
B. “CSF was injected intrathecally into three-day-old rat pups and subsequently the ultrastructural changes in the motor neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF causes fragmentation of the Golgi apparatus in a considerable number of motor neurons in the spinal cord. This was further confirmed when motor neurons were stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest that the putative toxin(s) present in ALS-CSF may cause impairment in the protein processing leading to motor neuron death. “ Ramamohan PY, Gourie-Devi M, Nalini A, Shobha K, Ramamohan Y, Joshi P, Raju TR.
C. “... earlier studies have shown that cerebrospinal fluid (CSF) of amyotrophic lateral sclerosis (ALS) patients causes death of motor neurons, both in in-vitro as well as in-vivo. There was an aberrant phosphorylation of neurofilaments in cultured spinal cord neurons of chick and rats following exposure to CSF of ALS patients (ALS-CSF). Other features of neurodegeneration, such as swollen neuronal soma and beading of neurites were also observed. In neonatal rat pups exposed to ALS-CSF, we observed phosphorylated neurofilaments in the soma of spinal motor neurons in addition to the increased lactate dehydrogenase activity and reactive astrogliosis. The present study examines the effect of ALS-CSF on the expression of glial glutamate transporter (GLT-1) in embryonic rat spinal cord cultures as well as in spinal astrocytes of neonatal rats. Immunostaining suggested a decrease in the expression of GLT-1 by astrocytes both in culture and in-vivo following exposure to ALS-CSF. Our results provide evidence that toxic factor(s) present in ALS-CSF depletes GLT-1 expression. This could lead to an increased level of glutamate in the synaptic pool causing excitotoxicity to motor neurons, possibly by triggering the 'glutamate-mediated toxicity-pathway'. Shobha K, Vijayalakshmi K, Alladi PA, Nalini A, Sathyaprabha TN, Raju TR.
D. “In the present study we show that there is an increased number of astrocytes intensely immunoreactive for glial fibrillary acidic protein (GFAP) in the gray matter of the spinal cords of neonatal rats exposed to ALS CSF. There is also increased expression of GFAP in the astrocytes of the white matter of neonatal rat spinal cords exposed to ALS CSF. Western blot analysis also confirmed the increased expression of GFAP. Accordingly, our study provides for the first time a clear evidence for the pathological response of glia to the circulating toxic factor(s) in the CSF of ALS patients.” Shahani N, Nalini A, Gourie-Devi M, Raju TR.

There are other studies, most cell culture or animal, which directly or indirectly indicate that the CSF of ALS patients contains compounds that are neurotoxic, inflammatory and proinflammatory, and otherwise contributory to pathogenic mechanisms common to ALS.

The impact of these CSF compounds can be summarized briefly as follows:

(1) Intracellular calcium is elevated in spinal cord neurons.
(2) Glutamate levels rise and receptors are activated in motor neurons.
(3) Some appear to lower quinine reductase levels in motor neurons and possibly astrocytes, which results in increased glutamate influx.
(4) Mitochondrial dysfunction occurs and with this compromised motor neuron energetics.
(5) Neuroinflammation increases.
(6) Antioxidant defenses such as glutathione are increasingly at risk of depletion or depleted.

Some of these effects overlap those of other players, both genetic and non-genetic, in ALS. As such, it is likely that therapeutic intervention with respect to modulating synthesis of neurotoxic, etc. compounds in the CSF or their impact on spinal cord and motor neurons, moderates the impact of these other players.

This aside, it follows that if some or most nonfamilial ALS patients owe at least part of their condition to damage wrought by various neurotoxic, inflammatory and proinflammatory, etc. compounds in their CSF, dietary, pharmacologic and nutraceutical measures that lower or otherwise modulate the synthesis of these substances or attenuate their impact on motor neurons will slow disease progression and prolong lifespan.

With this in mind, the author tooled together just such a regimen (2005 with subsequent modifications) consisting of:

CoQ10 (Ubiquinone/ubiquinol): Rationale for use – CoQ10 appears compromised in ALS. Dose: 200 mgs. every 2 hours during the day (1200 mgs daily)

Noni juice or capsules – Rationale for use: Contains a potent quinone reductase inducer – QR reduces glutamate toxicity in cells. Dosage: Juice to be drunk liberally all day long. Capsules – 1 every 2 hours during the day and 1-2 capsules one hour to one-half hour before bedtime.
Tumeric Extract Tablets or Capsules – Rationale for use: Quinone reductase inducer in astrocytes (Lowers glutamate). Dose: 1 (.05 gram) tablet every two hours during the day and 1-2 tablets prior to bedtime.
DEPRENYL: According to a 1994 animal study, “CSF samples from ALS and non-ALS neurological patients were injected into the spinal subarachnoid space of 3-day-old rat pups, followed by a single dose (0.01 mg/kg body weight) of (-)-deprenyl, administered 24 h after CSF injection. After a further period of 24 h, the rats were sacrificed and the spinal cord sections were stained with antibodies against phosphorylated neurofilament (NF, SMI-31 antibody) and glial fibrillary acidic protein (GFAP). Activity of lactate dehydrogenase (LDH) was also measured. (-)-Deprenyl injection resulted in a significant (61%) decrease in the number of SMI-31 stained neuronal soma in the ventral horn of the spinal cord of ALS CSF exposed rats. This was accompanied by a reduction in the astrocytes immunoreactive for GFAP. There was also a significant (35%) decrease in the LDH activity following (-)-deprenyl treatment. These results suggest that (-)-deprenyl may confer neuroprotection against the toxic factor(s) present in ALS CSF.” Shahani N, Gourie-Devi M, Nalini A, Rammohan P, Shobha K, Harsha HN, Raju TR.
Dose: Discretionary with each patient’s physician. Use of patches or oral forms (Pills, tablets or liquid). The typical daily dose was 12 mgs/daily.
IV Glutathione: Rationale – depleted in many ALS patients or at risk of becoming so. The intravenous (IV) dose is determined by each patient’s physician. During 2007 a patented oral form of glutathione became available, one that is absorbed through the oral mucosa and resists breakdown until it reaches the CNS (Th-Queen from Italy ).
PREVAGEN (Aequorin) – Rationale for use: Prevents calcium influx and resultant toxicity in neurons. Dose: One twenty milligram (20 mg) capsules every 2 to 3 hours during waking hours and one to two (1-2) capsules 30-60 minutes before retiring for the night. Aequorin became available commercially during 2007 and was added to the regimen at that time.
Lithium – Rational for use: Glutamate modulation in neurons. Dose: 250 mgs. to 600 mgs Lithium carbonate daily (Dosage determined by each patient’s neurologist or primary care physician). Lithium was added to the regimen during 2007.
Diet: Medium Chain Triglycerides Diet. Rationale: There are many reasons the ketogenic or MCT diets might be of benefit to ALS patients, not the least of which is the fact they tend to increase glutamate transporter gene expression.
Ketogenic & MCT Diet (Epilepsy website)
MCT Diets
Hypothesis Support – Clinical Responses (n=4)

Four individuals diagnosed with nonfamilial ALS (3 male, 1 female, ages 35-52) adopted the regimen outlined above beginning during 2005, all with their primary care physician or neurologist’s participation (Note that Prevagen was introduced during 2007 when it became available. Lithium was likewise added during 2007). All four experienced disease progression, however when compared to age- and disease matched controls, the degree of progression is decidedly less. One (male) patient noted that “Every single ALS patient diagnosed at the same time I was (diagnosed) is now dead or on a respirator. I am still walking, talking, eating and living my life. I’ve lost some functioning in my hands and arms, but this is not so great as to rob me of doing things I need to do like driving my car”.

While the responses of these six is far from definitive and cannot be called rigorous in the scientific sense, it is suggestive and offers a very tentative confirmation of the hypothesis put forward.

A greater degree of confirmation will come when, for example, the choroidal cells in the brains of ALS are replaced in whole or part by healthy counterparts produced from stem cells. In accordance with this hypothesis, it is expected that synthesis and circulation of a healthy CSF will result in a significant degree of disease progression or even disease arrest.



See also this variation of the regimen cited in this paper: Retarding ALS Progression



© 2008 by Dr. Anthony G. Payne. All rights reserved. The information contained in this article is provided for informational purposes only and should not be construed as medical advice or instruction. Readers are advised to consult a licensed health care professional concerning all matters related to their health and well being.

SORRY................

I HAVE BEEN BED RIDDEN BECAUSE OF THIS NEW DRUG-DMQ-I'M ON. IT IS PART OF THIS CLINICAL TRIAL. MY BLOG HAS BEEN LAME, I KNOW, BUT A FULL UPDATE ON ME TO COME......................

Neural stem cells are present in the adult human spinal cord

AN ARTICLE FROM MY FRIEND TOM FROM SPOKANE, WA-THANKS TOM

Neural stem cells are present in the adult human spinal cord
Jean-Philippe Hugnot (teacher-researcher at the University of Montpellier) Alain Privat (Inserm research director) Luc Bauchet (neurosurgeon) and their colleagues at Inserm Research Unit 583 have for the first time demonstrated the presence of neural precursor cells in the adult human spinal cord. The use of these stem cells for therapeutic purposes could potentially contribute to repairing the spinal cord of persons suffering from a traumatic injury, as well as in the case of a degenerative disease involving the motor neurons: amyotrophic lateral sclerosis (ALS). This work is published in The Journal of Neuroscience Research.
Some 40,000 people in France suffer from spinal cord injuries as a result of an accident. Each year there are 1,500 new cases of paraplegia or tetraplegia concerning for the most part 25-30 year-olds. The spinal cord is the part of the central nervous system that extends from the brain inside the spinal column. It ensures the proper working of an entire network of motor neurons that are vital not only to all our movements but also to the transmission of sensory signals and the control of visceral functions. Injuries affecting this neuron wiring are at the present time irreversible.
Researchers throughout the world are today subjecting stem cells to close scrutiny for their ability to differentiate in a given type of cell. They are in fact at the origin of all the cell types of the organism. These undifferentiated cells are present in the embryo. They are also present in the adult but are far less common and less pluripotent: adult stem cells present in tissue cannot, as a general rule, give a type of tissue other than their own.
The presence of neural stem cells in the brain and the spinal cord of adult rodents was shown several years ago, but it had not previously been possible, on the strength of current techniques, to detect such cells in the human spinal cord. Thanks to close cooperation with the Montpellier University Hospital and the Agence de Biomédecine, the researchers from Inserm have been able to work with tissues of excellent quality. Using techniques combining immunologic markers and electron microscopy, they have proved the presence of neural stem cells in the human adult spinal cord. Moreover, by cultivating these cells in vitro, the Inserm scientists have shown that the cells are capable of giving all the neuron cell types: neurons themselves but also glial cells (oligodendrocytes and astrocytes). Less known but just as important as the neurons, the glial cells provide nourishment and help to control neuronal activity. These precursor cells discovered in the spinal cord are of great therapeutic interest since they could compensate, via its use in gene therapy, for the neuronal and/or glial losses in traumatic lesions, neurodegenerative pathologies or those affecting the myelin sheath surrounding the neurons. Before therapeutic use can be envisaged, there is a need to explore the diversity of these cells and the details of their differentiation. "The therapeutic interest of so-called adult stem cells is now generally acknowledged by the scientific community. Although there is still a long way to go, this work constitutes a major step forward for all the pathologies affecting the motoneurons for which no treatment exists at the present time," says Alain Privat.
This research project on stem cells is being conducted within the framework of the European RESCUE consortium ("Research Endeavor for Spinal Cord in United Europe"), which seeks to indicate treatments for repairing spinal injuries responsible for paraplegia and tetraplegia.
Coordinated by Alain Privat, this project brings together 10 partners including the NEUREVA start-up in Montpellier and 6 European countries (Belgium, the Czech Republic, France, Germany, Spain and the United Kingdom). It is funded to the tune of EUR2.7 million as part of the 6th European Framework Programme for Research and Technological Development.


Further information
Source

Adult human spinal cord harbours neural precursor cells that generate neurons and glial cells in vitro. C. Dromard (1), H. Guillon (1), V. Rigau (2), C. Ripoll (1), JC Sabourin (1), F Perrin (1), F Scamps (1),S Bozza (1), P. Sabatier (5), N Lonjon (1,5), H Duffau5, F. Vachiery-Lahaye (3), M. Prieto (1), C Tran Van Ba (1), L. Deleyrolle (1), A. Boularan (4), K. Langley (1), M. Gaviria (1), A. Privat (1), J.P. Hugnot (1), L.Bauchet (1,5,6) (1) Inserm U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St ELOI, BP 74103 80, av Augustin Fliche 34091 Montpellier Cedex 05, France. (2) Service d'Anatomopathologie, CHU Montpellier, France. (3) Coordination hospitalière de prélèvement et Etablissement Français des Greffes, CHU Montpellier, France. (4) Département Anesthésie Réanimation C, CHU Montpellier, France. (5) Département de Neurochirurgie, CHU Montpellier, France. (6) Centre Propara Languedoc-Mutualité Montpellier, France J. Neurosc Res 2008 March 2008
Research contact
Alain Privat Directeur de recherche Unité Inserm 583 privat@univ-montp2.fr JP Hugnot Neural stem cell group Institut of Neuroscience of Montpellier Unité Inserm U583 hugnot@univ-montp2.fr Tel: 04 99 63 60 08

KR,

FROM NEW YORK------------- PLEASE EMAIL ME AT SCHEMERA@YAHOO.COM. WHEN YOU POSTED, IT DID NOT GIVE ME YOUR EMAIL AND I WOULD LIKE TO RESPOND TO YOU.

THANKS DREW

Test of maturity for stem cells

Test of maturity for stem cells
May 7th, 2008
Test of maturity for stem cellsStem cells can differentiate into 220 different types of body cell. The development of these cells can now be systematically observed and investigated with the aid of two new machines that imitate the conditions in the human body with unprecedented accuracy.Stem cells are extremely versatile: They can develop in 220 different ways, transforming themselves into a correspondingly diverse range of specialized body cells. Biologists and medical scientists plan to make use of this differentiation ability to selectively harvest cardiac, skin or nerve cells for the treatment of different diseases. However, the stem cell culture techniques practiced today are not very efficient. What proportion of a mass of stem cells is transformed into which body cells? And in what conditions? "We need devices that keep doing the same thing and thus deliver statistically reliable data," says Professor Günter Fuhr, director of the Fraunhofer Institute for Biomedical Engineering IBMT in St. Ingbert.Two prototypes of laboratory devices for stem cell differentiation enable the complex careers of stem cells to be systematically examined for the first time ever. These devices are the result of the international project ‘CellPROM' - ‘Cell Programming by Nanoscaled Devices' - which was funded by the European Union to the tune of 16.7 million euros and coordinated by the IBMT. "The type of cell culture used until now is too far removed from the natural situation," says CellPROM project coordinator Daniel Schmitt - for in the body, the stem cells come into contact with solute nutrients, messenger RNAs and a large number of different cells. Millions of proteins rest in or on the cell membranes and excite the stem cells to transform themselves into specialized cells. "We want to provide the stem cells in the laboratory with a surface that is as similar as possible to the cell membranes," explains Daniel Schmitt. "To this end, the consortium developed a variety of methods by which different biomolecules can be efficiently applied to cell-compatible surfaces."In the two machines - MagnaLab and NazcaLab - the stem cells are brought into contact with the signal factors in a pre-defined manner. In MagnaLab, several hundred cells grow on culture substrates that are coated with biomolecules. In NazcaLab, large numbers of individual cells, washed around by a nutrient solution, float along parallel channels where they encounter micro-particles that are charged with signal factors. "We use a microscope and a camera to document in fast motion how individual cells divide and differentiate," says Schmitt. The researchers demonstrated on about 20 different cell models that the multi-talents can be stimulated by surface signals to transform themselves into specialized cells.

ANOTHER ONE..................

Death stares at us all. All we can do is stare back & laugh.

FITTING...............

"To become strong in the broken places in our lives demands that we do two things, seeming opposites: hang in there, and let go."

A FELLOW PALS SENT ME THIS

Drew, thanks for the welcome and let me share this with you: " . . . . hope, as opposed to cynicism and despair, is the sole precondition for new and better experiences. Realism demands pessimism but hope demands that we take a dim view of the present because we hold a bright view of the future; and hope arouses as nothing else can arouse . . . ...a passion for the possible."
Gene

THIS IS GREAT...........................

It's compromise that moves us along

My heart is full and my door's always open

You can come anytime you want

Pixie dust helps finger regrow including nerves

Video http://news.bbc.co.uk/2/hi/health/7376191.stm

MY MAD JOURNAL

I LAUGH AND CRY AT ODD TIMES-LIKE WHEN I'M WATCHING A CRIME SHOW OR I'LL LAUGH AT TIMES WHEN LAUGHING HAS NO PLACE. LIKE WHEN I'M NERVOUS OR UPSET. THIS CHALLENGE HAS BROKEN ME DOWN AT TIMES WHEN I'M BROKEN AND TIMES WHEN I'M NOT. IT HAS MADE ME TEAR DOWN THE WALLS I BUILT AROUND MYSELF-THERE IS NO PROTECTION-NO WALLS-NO SUITE OF ARMOUR. IT HAS SLOWLY CHIPPED AWAY MY SELF RELIANCE. IT HAS NO END IN SIGHT TILL IT HAS ME TOTALLY RELIANT ON OTHERS AND THEN IT WILL TAKE THE ONE THING I HAVE THAT IS NOT RELIANT ON ANYONE--MY ABILITY TO TO BREATHE. THIS DISEASE IS EVIL....................
ANOTHER DAY OF ME MAD AS HELL

Clinical Trial Looks at Emotional Side of ALS

Clinical Trial Looks at Emotional Side of ALS

A research study is being conducted by Avanir Pharmaceuticals at 30 national study sites, including some of The ALS Association’s Certified Centers of Excellence to test drugs on people with ALS who frequently become overly emotional. People with pseudobulbar affect (unfortunately I have this, evidenced by my speech and I'm in this trial at Columbia-starts on may 9th) are being sought for approximately 30 U.S. study sites testing the efficacy and safety of a targeted investigational treatment known as Zenvia™ or AVP-923. The enrollment has started and is expected to end by the end of this year. In medical terms, the condition is referred to as pseudobulbar affect (PBA), which is characterized by uncontrollable laughing and/or crying. According to the Avanir Pharmaceuticals Web site, PBA affects more than one million people in the United States, including those who have been diagnosed with other neurological diseases such as multiple sclerosis, Parkinson’s disease, and dementias ranging from Alzheimer’s disease to stroke as well as traumatic brain injury. “People who suffer from PBA in many cases will curtail their social activities because they are embarrassed when they have these uncontrollable outbursts. By taking themselves out of social situations it could result in a change in their quality of life,” said Miriam Brodkin, program manager of patient services for The Association. Avanir Pharmaceuticals also states on its Web site that from 10% to 50% of people with neurological disorders suffer from PBA. The Web site states that PSA may occur when disease or injury damages the area of the brain that controls normal expression of emotion and that this damage can disrupt brain signaling causing a “short circuit,” triggering episodes of involuntary emotional expression. “This information may be extremely helpful to ALS patients suffering from the uncontrollable emotional outbursts associated with PBA,” said Ryan Arnold, associate director, clinical research, Avanir Pharmaceuticals.

Support cells modify Lou Gehrig's Disease

Support cells modify Lou Gehrig's Disease

By Deanna Chieco Issue date: 4/24/08

Glial cells, the supporting cells of the nervous system, are present everywhere in your brain and spinal cord and help with communication between neurons. Despite their supportive role in the healthy nervous system, these glial cells can undergo functional changes after a brain injury or during illness that make it harder for the nervous system to heal. A group of Hopkins researchers led by Nicholas Maragakis, a neurologist at the School of Medicine, examined the role of glial cells in the neurodegenerative disease amyotrophic lateral sclerosis, known as ALS or Lou Gehrig's Disease. ALS involves the progressive degeneration of motor neurons, which transmit signals from the brain that tell muscles what to do, and eventually leads to weakness, paralysis and death. The researchers examined how the growth or proliferation of astrocytes, a type of glial cell found throughout the central nervous system, could play a role in the cause of ALS. Following an injury, astrocytes undergo a process called reactive astrogliosis, in which they lose their normal functioning and exhibit altered gene expression. In a healthy nervous system, astrocytes play a supporting role which consists of regulating neurotransmitter and ion uptake as well as preventing toxins in the blood from reaching the brain. However, if astrocytes become reactive, they can lead to the death of their neighboring neurons because of the loss of vital functions. Working from previous evidence that reactive astrogliosis was important in neurodegenerative disorders, this group of researchers investigated a connection between the proliferation of these reactive astrocytes and ALS. They used two mouse models that were genetically modified to express either an acute or chronic form of motor neuron disease. Markers were used to label dividing astrocytes in tissue sections for each mouse model. Astrocytes and motor neurons in the lower region of the spinal cord were the main area of focus. The acute model represents the immediate cellular changes following a traumatic brain or spinal cord injury. In this model, they found that astrocyte proliferation was reduced in the disease model as compared to a wild-type mouse. However, if these proliferating astrocytes were ablated, or removed, there was not a significant decrease in the number of reactive glial cells. They concluded that proliferating astrocytes were not a large component of the reactive astrocytes contributing to acute motor neuron disease. The chronic mouse model, which implies a slower onset and progression of disease-like symptoms, is more representative of ALS. In this case, the number of proliferating astrocytes was also reduced but found not to be the main contributor to reactive astrogliosis. Additionally, if the proliferating astrocytes were ablated, the disease-like symptoms were retained, indicating that cell death of motor neurons was still occurring. In each of these models, there was an increase in the number of astrocytes present, though they may not have been actively dividing at the time. For a chronic disease like ALS, if large numbers of astrocytes proliferate over a long period of time, there could still be a significant effect on astrogliosis. Though the researchers did not find improved symptoms if proliferating astrocytes were ablated, they were able to better define the role of these astrocytes in terms of nervous system injury and degeneration. They determined that proliferating astrocytes are a relatively small contributor to the symptoms of the disease, but that they are in fact present in reactive astrogliosis.

THIS IS A GREAT STORY

"Maggie Miller"
Maggie and her husband live in Okemos, Michigan.The following is her self written journey with ALS.
Maggie and Stan
By Maggie Miller
My husband, Stan the Man, and I kissed goodbye in the neurologist’s parking lot and walked to our separate cars, still stunned at the possible diagnosis. As we drove back to work, each of us was clinging to the notion that all this would all go away when we met the doctors at the University of Michigan hospital for a second-opinion. (My Green blood churned.) We were determined to forget the news of the morning and eagerly, if not anxiously, buried our thoughts in our students’ lives.
It had been seven months since I first noticed that I slurred the word “counselor” when I would leave my voice mail message at my high school office. It was a “what’s up with that” situation I dismissed as battle fatigue! That summer my sister assumed that my progressively increased slurring was from too many pina coladas (nice job on alcoholic intervention, sis). Stan, who I like to believe lingers on my every word, said nothing. When I returned to school in August to mingle with colleagues, a friend asked if I had dental work done; another, if I had had a stroke. It was like being hit by a two-by-four—something was wrong (duh-ah). I freaked out. Whatever this was, it was out.
After many delightfully-comfortable tests, the doctor at U of M Motor Neuron Disease Center confirmed the diagnosis of bulbar onset ALS and launched into discussions of three-month visits and future losses. It was “an out of body experience” as I received what seemed like reams of hardcopy to read (or shove under my bed--me bad) and met a parade of specialists who would be my clinical team. I don’t remember the ride home or the remainder of that week. I sat on the porch coma like, did not go to work (which was a rarity for me), cried and laughed with friends who stopped by and decided that I would give myself ONE WEEK to grieve this stupid inconvenience. I then returned to work as usual so that my students would not miss a beat in whatever they needed me for.
As the year progressed, we created a dictionary on the white board of our work room. Whatever I tried to say was posted, followed by the translation. It was quite hysterical. “Mouth-breather” became “moth breeder.” “Beth” was “Bef” and “Sara” was “Sawah.” The others are highly kept secrets. I napped on a floor mat (thanks to Sawah and Bef) by my desk during lunch to battle increasing fatigue.
By May I was typing my responses on my computer during student and parent meetings, e-mailing (my least favorite means of communicating) instead of “phone mailing,” relinquishing my stand-up presentations to my wonderfully supportive colleagues and still helping my students deal with their issues and, surprisingly, with my illness. The end of the school year brought the end of my career.
Two years later, I have finally come to terms with this damn disease. I once described the diagnosis as having been given a new skin that at times was so tight I could barely move and at other times so loose that I got lost in the many crevasses and folds. I have grown into it now and, although not stunning in appearance, it is me. I have grieved my major loss—not being able to work with kids—and learned to deal more effectively and realistically with my life as a person with ALS, not a person fighting the disease as if it were Darth Vader. Stan, my pals and I still joke about Big AL(s), which is our way of dealing with what lies ahead or what was left behind.
My life has been one of an idealistic thinker and talker, a story teller, an entertainer, a comedian, a person with a contagious smile and laugh and a good-natured prankster. My second most favorite thing in the whole world, next to working with teenagers, was eating good food while laughing and bantering with friends over great meals and drinks.
Today, I cannot speak, eat, drink, smile, swallow or hold my neck erect without support—but I can still walk, move my arms, drive and hug back! I consider myself fortunate when compared to other ALS patients. I have an outstanding team of caring and compassionate medical professionals at the U of M clinic and an amazing support system stationed around the country.
So life as I knew it has changed. Stan, our families, my pals, including former colleagues and students from as long ago as 30 years, have been tremendously attentive, generous and patient with me. An Okemos High School community service club, All Connecting to Improve Our Neighborhoods, has sponsored three bowl-a-thons in my honor, raising more than $25,000 for ALS research.
I return to the high school often (as if they could keep me away). I have spoken twice a year to the English classes after they read Tuesdays with Morrie. When it snows hard, I still turn my jammies inside out to encourage the snow-day voodoo. E-mails (now my favorite method of communication), visits, help with things I can no longer do and outings bofriendships. ost my spirits. My one-liners take longer to deliver as I type them into my Dynawrite (aka “Paul”), but I am still as feisty as ever. I have become a better listener and more thoughtful responder. I have grown closer to my family and have rekindled
The kindnesses and generosity I have experienced, kudos from my professional organizations, innumerable letters of appreciation and awards I have received are usually shared at memorial services. I am alive to experience them all with my entire heart and soul.
I am the lucky one!

$115M stem cell research facility planned for San Diego

$115M stem cell research facility planned for San Diego
Mon Apr 21, 6:28 AM ET
A new nonprofit institution plans to build a $115 million stem cell research facility in San Diego that would open by 2010.
Although funding still is being lined up, the San Diego Consortium for Regenerative Medicine proposes constructing a 23,740-square-foot building housing laboratories and support space.
The facility would be located on more than 7 acres owned by the University of California at San Diego in the Torrey Pines area biotechnology cluster.
The university is one of four members of the consortium. The others are the Burnham Institute, Salk Institute and Scripps Research Institute.
The state is expected to provide a large portion of the facility's funding. Californians in 2004 approved a measure creating a $3 billion stem cell research agency.
A panel for the state agency has determined the San Diego consortium is eligible for $43 million. A condition to receive the state funds is that the building be completed by 2010.
Consortium officials estimate they would need to raise at least an additional $72 million to complete the center's funding. They said an out-of-state donor whom they decline to name has agreed to contribute $30 million.
"I believe strongly that this consortium will, in time, lead to significant scientific advances and life-saving results," said Marye Anne Fox, chancellor of UC San Diego.
Human embryonic stem cells are created in the first days after conception and give rise to all organs and specialized tissues in the body. Many social conservatives oppose the work because human embryos are destroyed during research. Scientists lately have created the equivalent of embryonic stem cells from ordinary skin cells, an embryo-free technique.

Yeast rises to the occasion: Penn researchers find potential in yeast for selecting Lou Gehrig’s disease drugs

April 18, 2008
Yeast rises to the occasion: Penn researchers find potential in yeast for selecting Lou Gehrig’s disease drugs

PHILADELPHIA – Researchers from the University of Pennsylvania School of Medicine are developing a novel approach to screen for drugs to combat neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, using yeast cells.
In recent months a number of mutations have been found in a disease protein called TDP-43, which is implicated in ALS and certain types of frontotemporal dementia (FTD).
“We've created a yeast model, the same cells that bakers and brewers use to make bread and beer, to express TDP-43,” explains lead author Aaron D. Gitler, PhD, Assistant Professor of Cell and Developmental Biology. “Remarkably, this protein formed clumps in our simple yeast cells just like it does in human nerve cells. In our paper we determine which segments of the mutated TDP-43 protein cause it to aggregate and which parts cause it to be toxic.” Gitler and colleagues report their findings in this week’s advance online issue of the Proceedings of the National Academy of Sciences.
Two years ago, other Penn investigators found that TDP-43 accumulated abnormally in post-mortem brain or nervous system tissue from individuals diagnosed with either ALS or FTD. TDP-43 is normally involved in RNA and DNA processing, among other cellular tasks. The recent TDP-43 mutation studies confirm the protein’s role in causing disease.
The clumping process of proteins takes decades in humans but the researchers could model the process within a matter of hours in yeast cells. This now allows for rapid genetic screening to identify proteins that can reverse the harmful effects of the disease protein; visualizing the clumping; and testing molecules that could eliminate or prevent clumping.
“Our yeast model will be a powerful tool for performing large-scale drug screens to look for small molecules that can prevent TDP-43 from aggregating or that can protect cells from aggregated TDP-43,” notes Gitler.
Normally, TDP-43 stays in the nucleus, but in ALS and FTD it somehow gets sequestered into the cell’s cytoplasm, where it forms clumps. “When we put TDP-43 in yeast cells at normal human levels, it remained in the nucleus,” explains Gitler. “However, when it was expressed at higher levels, thereby overwhelming the quality control systems of the cell, TDP-43 clumped in the cytoplasm. At even higher levels, TDP-43 became toxic to the yeast cells, making them unable to grow.” This experiment suggests, for the first time, that TDP-43 clumps can be a direct cause of cell toxicity.
In earlier studies at Penn, researchers found fragments of TDP-43 that were abundant in the clumps found in the post-mortem tissue of ALS and FTD patients. Knowing this, Gitler and colleagues chopped TDP-43 into many fragments to find the segments that are responsible for clumping and toxicity. They found a very similar segment that was also toxic to yeast cells. Designs of future drugs will depend on what part of the TDP-43 protein needs to be disabled.
The researchers are able to overexpress every yeast gene to determine which genes can rescue the yeast cells from the TDP-43 toxicity. In addition to these genetic screens, Gitler and colleagues are pursuing drug screens with their TDP-43 model. “We can screen hundreds of thousands of small molecules to see which can get into a yeast cell and prevent TDP-43 from being toxic,” says Gitler. “Then we can take the hits we find and test them in animal models. We have already made mutations identical to what have been found in patients and have introduced those in the yeast model.”
Co-authors are Brian S. Johnson from Penn, J. Michael McCafferty, from Johns Hopkins, and Susan Lindquist, from the Whitehead Institute for Biomedical Research (MA). The research was funded in part by a pilot grant from the University of Pennsylvania Institute on Aging.

PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
© 2008 University of Pennsylvania

I WROTE THIS LAST NIGHT..........

IT’S A HARSH WAKE UP CALL WHEN YOU SEE/HEAR OF SOMEONE THAT IS FARTHER ALONG IN THEIR DISEASE AND YOU KNOW YOUR JOURNEY IS MOST LIKELY HEADED THAT WAY. I CAN BELIEVE TILL THE COWS COME HOME THAT EVERYTHING IS GOING TO BE OKAY-AND BELIEVE ME, I DO THINK AND HOPE TO THE HIGH HEAVENS THAT THIS JOURNEY IS A BRIDGE TO SOMETHING GRAND-SO GRAND THAT I WILL LOOK BACK ON THIS AND KNOW I'M A BETTER MAN FOR HAVING COMPLETED THIS JOURNEY....... BUT THAT DOES NOT GUARANTEE ANYTHING. MAKE NO MISTAKE MY ATTITUDE AND HEART ARE NEVER IN QUESTION-I’M JUST A REALIST AND EVERY ONCE IN AWHILE I GET THIS SICK FEELING THAT THIS IS NOT GOING TO TURN OUT WELL. SO THE BEST THING I CAN DO IS PUT IT DOWN ON PAPER AND LET IT ALL HANG OUT. THIS IS MY THERAPY. THIS IS ME UN-FILTERED. THIS IS MY NAKED MIND FOR ALL TO READ.

THANKS FOR LISTENING-IT’S NOW 11:15PM AND MY BED IS CALLING.

I TAKE 2400MG A DAY-GLAD TO KNOW IT'S WORKING

http://www.npicenter.com/anm/templates/newsATemp.aspx?articleid=21043&zoneid=2

CBS-TV News Feature Reports on the Promising Results of a Recent Cognizin Study-2008/04/15 - Kyowa Hakko

(New York, NY) April 14, 2008 – A report by WBZ-TV, the CBS-TV affiliate in Boston, focusing on the most recent Cognizin Citicoline study, is being fed to all CBS-TV news affiliates nationwide. The news feature includes an interview with Dr. Perry Renshaw, director at McLean Hospital and professor at Harvard Medical School on the Cognizin study which demonstrated the patented supplement’s positive impact on the cognitive skills of healthy, middle aged adults. To view the CBS-TV report and accompanying article, visit www.cognizin.com.
Kyowa Hakko is an international health ingredients manufacturer and world leader in the development, manufacturing and marketing of pharmaceuticals, nutraceuticals and food products. The maker of the branded ingredients Cognizin® Citicoline, Resilen™ Hyaluronic Acid , Lumistor® L-Hydroxyproline, Kyowa CoQ10®, Setria® Glutathione and Sustamine™ Alanyl Glutamine, Kyowa offers manufacturers and formulators one of the industry’s most extensive lines of over 50 amino acids and related compounds, including D-Amino acids and branch-chain amino acids, as well as nucleic acids, bio-products and fine chemicals.
# # # #
Dr. Perry RenshawDr. Perry Renshaw, M.D., Ph.D. is director of the Brain Imaging Center at McLean Hospital and professor of Psychiatry at Harvard Medical School. He is the leading scientific researcher on the health benefits of Citicoline. Dr. Renshaw attended the University of Pennsylvania School of Medicine where he received his Ph.D. in biophysics and his M.D.Media Note: For further information, or to schedule an interview, please contact Karen Todd at 734.214.2296 or todd@kyowa-usa.com. For more information about Kyowa Hakko visit www.kyowa-usa.com.

A RULE TO LIVE BY

"Life: It's a rugged road! But if we don't surf the waves, we are under them!"

In my own life "study",

I find that if I slow down, ALS speeds up.

Gotta keep movin'.

Resistance exercise slows functional decline in amyotrophic lateral sclerosis

Supervised Resistance Exercise Slowed Functional Loss in Small Study
by Amy Labbe
People with early-stage ALS who engaged in a supervised resistance exercise program had better muscle function after six months than a similar group that participated only in a stretching program, say U.S. and Canadian researchers who recently conducted a 27-person study.
Although the debate persists over whether or not exercise is beneficial or detrimental in ALS, these latest study results represent a potential first step toward resolving the long-standing controversy.
The research team, which included a physician and physical therapists associated with MDA/ALS Centers in New York and St. Louis, found that, even though exercise may not have any ultimate influence on disease progression, it may temporarily slow loss of strength and function and minimize muscle wasting that results from lack of movement.
In a paper published in the June 5 issue of Neurology, the investigators say they randomly assigned 13 out of 27 subjects with mild to moderate weakness to a regimen of stretching and resistance exercise. They assigned the other 14 to a control group that performed only stretching exercises. Eight people in the stretching-plus-resistance exercise group and 10 in the stretching group completed the trial.
Physical therapist Jeanine Schierbecker assesses the strength of a man with ALS.
The stretching routine was the same for both groups and was performed daily, while those in the resistance exercise group added individualized exercises using cuff weights three times a week.
After initial instruction, all exercises were performed at home, with telephone monitoring every two weeks and physical assessments every month.
After six months, those in the resistance exercise program had a smaller decline in muscle strength than those performing only stretching exercises.
"Our study, although small, showed that the resistance exercise group had significantly better function, measured by the ALS Functional Rating Scale and upper and lower extremity subscale scores, and quality of life without adverse effects as compared to subjects receiving usual care," said study author Julaine Florence, a physical therapist at Washington University in St. Louis.
Physical therapist Jeanine Schierbecker, also a study author and physical therapist at Washington University, said her "best recommendation is that, if a patient with ALS is interested in pursuing an exercise program, they should discuss it with their physician and be evaluated by a knowledgeable, ALS-savvy physical therapist."

you gotta roll with the punches baby...................

You can't control the wind, but you can adjust your sails.

Neuratax: A unique Motor Neuron Disease product.

Good news for Motor Neuron Disease sufferers

http://www.neuratax.com/product.html

Fortunately for Motor Neuron Disease sufferers studies of the main and established traditional texts consistently highlight a number of plants and herbs for their ability to heal Motor Neuron Disease. Researchers at Botanical Sources having mined these texts finalized a list of the most effective plants and herbs for Motor Neuron Disease. A list of these plants and herbs with their specific properties can be found here (Please click). The most effective parts of the plants (e.g. stem, seed, leaves, roots etc) and the manner of extracting their inner content were established. As a result, we are now able to form a calculated mixture of these pure natural extracts in the form of an oral pill highly efficacious for Motor Neuron Disease. Where modern science has helped is firstly in establishing proper therapeutic dosage and secondly in testing the product for safety and side effects.
Following FDA and DSHEA guidelines at all stages of development we are now able to present what we believe is the most proven, effective, safe and easy to use product for healing Motor Neuron Disease and titled it Neuratax.

German lawmakers ease limits on stem cell research

German lawmakers ease limits on stem cell research
By Kerstin GehmlichFri Apr 11, 10:46 AM ET

German lawmakers voted on Friday to ease restrictions on stem cell research although the approved changes did not go as far as many scientists had hoped.
Under the bill approved by the Bundestag lower house of parliament, researchers will be allowed to import stem cells created before May 1, 2007, rather than only use cells existing before 2002, as current law prescribed.
Stem cell research is a divisive issue in Germany, in part due to Nazi genetic experiments linked to creating a "master race."
Scientists say stem cells offer the potential to treat conditions such as diabetes and Parkinson's disease and to regenerate damaged organs. Opponents of the research say it is unethical and involves the destruction of living embryos.
Following an emotionally-charged debate, 346 lawmakers voted in favor of the more recent cut-off date, and 228 against it.
Technology Minister Annette Schavan was among those who had backed the new 2007 deadline, saying Germany had to ensure its scientists could keep up globally.
"I think ... moving the date is right so as to maintain the small corridor for research which the 2002 stem cell law provided," she told parliament ahead of the vote.
Six years ago, the German parliament banned the production of embryonic cells from pre-existing stem cell lines.
To ensure foreign laboratories did not produce cell lines for the German market, it also barred German scientists from working on any lines created after January 1, 2002.
Scientists had complained that German restrictions prevented them from keeping up with global advances and some researchers had called for current restrictions to be scrapped altogether.
German laws are tighter than in some other European countries, including Britain and Sweden, and researchers have expressed frustration that they cannot take part in international projects using lines created after 2002.
The German Research Foundation (DFG) said young scientists were at risk of moving abroad if rules remained too restrictive.
"There are more than 500 cell lines worldwide, but German researchers are only allowed to use 21 old cell lines, which are in part contaminated and have developed in such a way that in some cases they are no longer comparable," DFG vice president Joerg Hinrich Hacker told ZDF television.
Many of those who believe life begins at conception say cells should be harvested from adults, not embryos. The German Bishops' Conference had warned against softening the law.
"Freedom of research must not be weighed against the fundamental protection of life," said Archbishop of Freiburg Robert Zollitsch, who heads the Conference.
German lawmakers on Friday voted against two other, more radical proposals on stem cell research -- one calling for a ban on all embryonic stem cell research, the other suggesting the cut-off date should not only be changed, but scrapped entirely.
(Reporting by Kerstin Gehmlich; Editing by Matthew Jones)

TELL-TALE PROTEIN CLUMPING IN ALS IS LESS COMPLEX THAN EXPECTED

From: alscenter@jhmi.edu
To: The ALS Community Date: April 10, 2008 Subject: Robert Packard Center ALS News
Network Article available online at:http://www.alscenter.org/news/briefs/080410.cfm

TELL-TALE PROTEIN CLUMPING IN ALS IS LESS COMPLEX THAN EXPECTED
That could be a good thing for potential therapies, researchers sayMore than a decade ago, when scientists uncovered a mutant gene for onetype of heritable ALS and saw that its resulting protein, calledsuperoxide dismutase (SOD1) was also flawed, they beheld their firstclue to the cause of the vile disease. More exciting, even, was the possibility * because of similarities inall forms of ALS * that the find would ultimately lead to therapy.Today, while cell and animal models of ALS engineered with the mutanthuman SOD1 gene have vastly advanced knowledge, the answers on howflawed SOD1 contributes to motor neurons' downfall lie just out ofreach. This March, however, a U.S. research team including Packard Centerbiochemist/neuroscientist David Borchelt brought the truth of theSOD1-ALS connection closer. In two studies reported in the Journal of Biochemistry, the scientistsperformed the first in-depth analysis of abnormal, microscopic clumps ofmutant SOD1 protein that form in motor neurons. They also clarifiedcell mechanisms that produce them. Protein aggregates are a hallmark of Parkinson's and Alzheimer's andother neurodegenerative diseases. Though the makeup and timing of thedeposits varies according to disease, the fact that they're toxic seemscertain. In ALS, aggregates appear both in animal models and in humanswith the disorder. And earlier animal model work in Borchelt's lab hasshown that clumped mutant SOD1 appears with the onset of diseasesymptoms. Until now, however, no one had closely analyzed the aggregates. Knowing their makeup could provide clues to the process that made themand, ultimately, perhaps, explain why they're toxic.In one study, Borchelt and a scientific team at UCLA, led by JulianWhitelegge and Joan Valentine, extracted aggregated SOD1 from spinalcords of three different varieties of mutant SOD1 mice, all of whichwere models for ALS. Using a variety of biochemical techniques, including mass spectroscopyand sophisticated chromatography, they showed mutant SOD1 to be the onlyprotein found consistently in the clumps. "This suggests thataggregating comes naturally to abnormal SOD1 molecules," Borchelt says;"by itself, then, mutant SOD1 could be responsible for the masses we seein cells." The clumping might be part of cell attempts to compact theprotein so its toxic portions are hidden. "We won't know what the clumps do, though, until we find how to keepthem from forming," he adds.
To that end, the scientists are investigating what triggers aggregates.Earlier work hinted that oxidative stress * the sort of insult that anumber of environmental events can deliver * might have a role inmaking mutant SOD1 "sticky." But this new research says that's unlikely,that something intrinsic in the molecule is at work. "These studies will help us identify the events crucial to generatingsubstances toxic to cells in ALS," says Borchelt, "while they'll alsoreveal chemical targets most likely to respond to therapy."
Packard scientist Borchelt heads the McKnight Brain Institute at the University of Florida, Gainsville.==========================About The Robert Packard Center for ALS Research at Johns Hopkins http://www.alscenter.org/

Knopp NeuroSciences Initiates Phase 2 Study of KNS-760704 in Amyotrophic Lateral Sclerosis

Apr. 07, 2008-

-Knopp Neurosciences Inc. ("Knopp") said it initiated the first Phase 2 study of KNS-760704 in patients with amyotrophic lateral sclerosis (ALS).

Additional study details are available www.clinicaltrials.gov

http://www.informaworld.com/smpp/content~content=a788680908~db=all~jumptype=rss

http://www.knoppneurosciences.com

The study is designed as a two-part, randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of KNS-760704 oral tablets. It will be conducted at approximately 20 centers in the U.S.
In Part 1 of the study, approximately 80 ALS patients from ages 21 to 80 whose symptoms started within the past two years will receive 12 weeks of treatment with low-dose, mid-dose, or high-dose KNS-760704 or matching placebo. Participants who complete Part 1 will be eligible for a Part 2 extension in which they will be re-randomized and will receive up to 28 weeks of treatment with either low-dose or high-dose KNS-760704.
Additional study details are available at www.clinicaltrials.gov.
Knopp said it plans to initiate a larger proof-of-concept study in 2009 if KNS-760704 is shown to be safe and well-tolerated in this Phase 2a study.
"Following the successful completion of our Phase 1 healthy volunteer studies in late 2007, we're pleased to be advancing KNS-760704 into clinical trials for ALS patients," said Michael Bozik, M.D., president and chief executive officer of Knopp. "This step represents another important milestone for Knopp in our efforts to develop an effective treatment for this relentless disease."
About KNS-760704
KNS-760704 is a chirally pure oral formulation of the synthetic amino-benzothiazole (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazolediamine dihydrochloride monohydrate in clinical development for the treatment of amyotrophic lateral sclerosis (ALS). Like its S(-) optical enantiomer, pramipexole dihydrochloride (Mirapex(R)), KNS-760704 has been shown to be effective in a range of neuroprotective assays. Unlike Mirapex(R), a selective, high affinity dopamine agonist approved for the treatment of Parkinson's disease, KNS-760704 exhibits very limited dopamine receptor affinity, making it possible to clinically evaluate its potential neuroprotective activity over a broad dose range. The compound's use in ALS has received orphan drug designation from the U.S. Food and Drug Administration. Phase 1 studies in healthy volunteers have been completed.

I FOUND THIS ON THE PATIENTSLIKEME.COM SITE

IT MAKES YOU THINK...... AND ASK WHY.................


A man went to a shop, picked up a beautiful cup and said ‘My God! This cup is so beautiful’. Suddenly the cup started talking.
“Oh man, I am beautiful right now, but what was the state of my being before the pot-maker made me so beautiful? I was sheer mud when the potter pulled me out from mother earth. I felt wreathed in tremendous pain wile being separated from mother earth. But potter said, ‘just wait’. Then he churned me. I felt giddy when I was churned, and asked ‘why are you so cruel?’ he said ‘just wait’. Then he put me in an oven & heated me up. I felt completely burnt. There was tremendous pain and I asked again ‘why are you so cruel?He said ‘just wait’. After that he poured hot paint on me and I felt the fumes and irritation. I again asked ‘ why are you so cruel? He again said ‘just wait’. He put me into an oven and again heated me to make me strong, I felt life was so painful hence pleaded with the potter to leave me free. He said ‘ just wait’. And finally he took me to a mirror and said “now look at urself’. Lo, what a change! I found myself so beautiful.”
When you feel the pain, it means god is working on us to improve us-
THIS IS MY ANSWER-----------really, GOD, is that what you're doing?

FDA to take key stem-cell step

FDA to take key stem-cell step

Government advisors meet this week to discuss designs for embryonic stem cell testing in humans.

By Aaron Smith, CNNMoney.

http://money.cnn.com/2008/04/08/news/companies/stem_cell/?postversion=2008040915

"THE LAST LECTURE"-RANDY PAUSCH

“We cannot change the cards we are dealt, just how we play the hand.”—Randy Pausch
BOY, IS THAT TRUE!!!!!!!!!!!!!!!!!!
FOR THOSE THAT MISSED THIS LECTURE-HERE IT IS AGAIN-HE WAS ON TONIGHT--CH.7-W/ DIANE SAWYER

TREMENDOUS COURAGE-I WATCH THIS EVERY NOW AND AGAIN TO KEEP ME POSITIVE. IT'S ABOUT ACHIEVING YOUR DREAMS....................It's about the importance of overcoming obstacles, of enabling the dreams of others, of seizing every moment (because “time is all you have...and you may find one day that you have less than you think”). It's about living.

http://www.youtube.com/watch?v=ji5_MqicxSo

ALS Therapy Development Institute Signs Collaboration Agreement with the Allen Institute for Brain Science

ALS Therapy Development Institute Signs Collaboration Agreement with the Allen Institute for Brain Science

Long-term arrangement between two leading non-profit research institutes designed to validate drug targets for the fatal neurodegenerative disease that affects 30,000 Americans

CAMBRIDGE, Mass. - April 08, 2008 - The ALS Therapy Development Institute (ALS TDI) today announced it has entered into an agreement with the Allen Institute for Brain Science in Seattle, Wash. for in situ hybridization (ISH) services using diseased tissues from a preclinical animal model of amyotrophic lateral sclerosis - ALS, or Lou Gehrig's disease. ALS is a progressive and fatal neurodegenerative disease with no known cause or cure. Under the terms of the agreement, the Allen Institute will perform ISH for genes, in the spinal cord, identified by ALS TDI researchers as being associated with the disease's progression. The aim of this work is to identify cells that are associated with changes in gene expression so that treatments can be directed towards those cells specifically. "The ongoing data mining efforts at the ALS TDI are identifying hundreds of therapeutic targets that need to be evaluated in vivo. Identification of cells to be targeted by treatments is a crucial step in therapeutic development," said Steven Perrin, Ph.D., Chief Scientific Officer of ALS TDI. "The publication of the Allen Brain Atlas-Mouse Brain project established the Allen Institute as leaders in ISH technologies and capabilities."At the end of 2007, ALS TDI completed an enormous database of transcriptome information for the SOD1 mouse model, the leading mouse model used internationally by ALS researchers. ALS TDI, a leader in translational research for ALS, has also initiated a similar project and experiment collecting blood samples from people living with the disease today and is expected to expand their collection project and experiments to include other tissues. Through a multi-year funding partnership with the Muscular Dystrophy Association and its Augie's Quest Initiative, ALS TDI expanded its research program to include the largest genomic research program in the history of the disease."The goal of the collaboration is to determine exactly where in the spinal cord the genes associated with the progression of ALS are active," said Elaine Jones, Chief Operating Officer of the Allen Institute for Brain Science. "Helping scientists worldwide accelerate their research programs is central to our mission. We're thrilled to be working with ALS TDI to help advance ALS research." The first samples will arrive from ALS TDI to the Allen Institute in April 2008. A progress report will be provided as part of an annual Leadership Summit and research symposium hosted by ALS TDI in Boston, Mass. on October 20, 2008.

About ALS Therapy Development Institute The ALS Therapy Development Institute (http://www.als.net/), based in Cambridge, Mass., operates the world's largest research and development program focused exclusively on ALS. Its staff of 30 scientists and research technicians work on behalf of ALS patients to discover and advance novel therapeutics for treating and ultimately curing ALS. The non-profit biotechnology institute excels in identifying novel disease targets, discovering compounds that may act against these targets, and screening potential treatments for clinical development. For more information, visit http://www.als.net/ or call 617.441.7200

About the Allen Institute for Brain ScienceLaunched in 2003, the Seattle-based Allen Institute for Brain Science is an independent, 501(c)(3) nonprofit medical research organization dedicated to advancing brain research. Started with $100 million in seed money from philanthropist Paul G. Allen, the Institute takes on projects at the leading edge of science-far-reaching projects at the intersection of biology and technology. The resulting data create publicly available resources that fuel discovery for countless other researchers worldwide. The Institute's data and tools are available on the web free of charge at http://www.alleninstitute.org/.

About Augie's Quest Fitness pioneer Augie Nieto started Augie's Quest (http://www.augiesquest.org/) in conjunction with MDA's ALS Division. Nieto is co-founder and former president of Life Fitness of Chicago, and chairman of Octane Fitness. He and his wife, Lynne, serve as co-chairpersons of MDA's ALS Division. Nieto received a diagnosis of ALS in March 2005.

About MDAMDA (http://www.mda.org/) is the world's largest provider of ALS services and funder of ALS research. Over the years, it has expended almost $200 million in this effort. It operates 225 neuromuscular disease clinics across the country and 37 ALS-specific research and care centers. __________________

Bidders up: Lou Gehrig's cap goes up for Internet bidding on May 6

HERE IS THE HAT

I THOUGHT THIS WAS COOL........

Bidders up: Lou Gehrig's cap goes up for Internet bidding on May 6
BY LARRY McSHANE DAILY NEWS STAFF WRITER
Sunday, April 6th 2008, 8:17 PM


During a 1939 visit to the Mayo Clinic, where he was diagnosed with the disease that would kill him, Lou Gehrig presented one of his doctors with a gift - a game-worn Yankees cap.
It was a typical gesture by the gracious Gehrig, "The Iron Horse" surrendering his wool cap to Dr. Paul O'Leary. The rare vintage hat with its familiar interlocking "NY" is now going on the auction block.
The cap, worn by Gehrig during his 2,130 consecutive-game streak, comes with a presale estimate of $125,000 - more than triple his top annual salary of $39,000 during his Yankees career.
The hat was most likely presented to O'Leary during the 1939 visit when Gehrig was diagnosed with amyotrophic lateral sclerosis. O'Leary continued to treat Gehrig afterward, with the two exchanging letters about his condition.
"You don't need me to tell you that game-worn Gehrig items are extremely hard to come by, and we are proud to offer this relic from one of the all-time Yankee greats," said Lelands.com Chairman Joshua Evans.
The Internet bidding on the hat begins May 6 and runs through June 6 at Lelands.com.
The cap, with a hard brim and a nicely worn look, was made by A.G. Spalding & Bros., according to the auction house. It is embroidered inside with the Yankee great's name and hat size: "7 1/8 L. Gehrig."
Gehrig, a two-time American League MVP, delivered the most memorable speech in stadium history after he was diagnosed with ALS, which is now also called Lou Gehrig's Disease.
"Today I consider myself the luckiest man on the face of the earth," the dying Gehrig told a sold-out crowd on July 4, 1939.
Gehrig had ended his consecutive games played streak just two months earlier; he was dead less than two years later.
lmcshane@nydailynews.com
http://www.nydailynews.com/sports/baseball/yankees/2008/04/06/2008-04-06_bidders_up_lou_gehrigs_cap_goes_up_for_i.html

A QUOTE THAT IS APPLICABLE FOR MY CHALLENGE

THIS IS AN OLD SPEECH-1993 ESPY'S BUT IT STILL IS APPLICABLE TODAY AND FOREVER. I LISTEN TO THIS ONCE A WEEK. GREAT STUFF....................

I WILL ECHO A QUOTE FROM JIM VALVANO AND I WILL CHANGE ONE WORD-CANCER TO ALS. IT IS SO TRUE!!

"ALS CAN TAKE AWAY ALL MY PHYSICAL ABILITIES--IT CANNOT TOUCH MY MIND--IT CANNOT TOUCH MY HEART--IT CANNOT TOUCH MY SOUL AND THOSE THREE THINGS WILL CARRY ON FOREVER"

HERE IS THE WHOLE SPEECH-IT WILL TUG AT YOUR HEART;

http://www.youtube.com/watch?v=ePXlkqkFH6s

MY SIS SENT ME THIS

"Fear is a Reaction, Courage is a Decision"

You can do very little with faith, but you can do nothing without it.

2-way cell talk provides clues about neuromuscular disease

2-way cell talk provides clues about neuromuscular disease

It’s a scientific given that neurons tell other cells what to do, but new evidence suggests that, like with any good relationship, these target cells also have much to contribute, scientists say.
In an animal model, Medical College of Georgia researchers have shown that if a muscle cell fails to produce the protein beta-catenin, its neuron doesn’t develop or function properly. Their finding provides some of the first proof that in vertebrates such as man, this retrograde communication – from the target cell back to the neuron – is essential, says Dr. Lin Mei, corresponding author on research published online Sept. 17 in Nature Neuroscience. “Previously, we thought signals flow mainly from neuron to muscle. This shows they can be produced from muscle,” says Dr. Mei, MCG’s chief of developmental neurobiology and Georgia Research Alliance Eminent Scholar in Neuroscience. “This is some of the first clear genetic evidence that when you disturb something in the muscle, you have a nerve problem.” Dr. Mei’s research team knocked out beta-catenin in the muscle cells of a developing mouse. As a result, nerve terminals, which reach out to target cells, were misaligned. Release of neurotransmitters, which enable cell talk, from the tiny vesicles inside nerve terminals was impaired. Mice died prematurely. “Two-way communication is absolutely essential,” he says. Interestingly when the researchers knocked beta-catenin out of neurons instead, neurons developed and functioned normally. “Theoretically the finding is very important in that it supports the retrograde hypothesis,” Dr. Mei says. “Practically it is also important because problems with motor neuron survival and differentiation cause many neuromuscular diseases, such as muscular dystrophy and ALS, where motor neurons need to survive,” noting that it’s unknown why neurons die in these diseases. “We believe there is a retrograde signal downstream of beta-catenin or regulated by beta- catenin,” says Dr. Mei. “If you don’t have beta-catenin in the muscle, that signal may be missing and motor neurons are not happy.” To find out what that signal is, his lab is comparing genetic expression in the beta-catenin knockout mouse to that of a normal mouse to see which genes are up- or down-regulated. “Those genes may be targeted by beta-catenin and may serve as this retrograde signal. If we can identify that, I can retire,” says Dr. Mei. Beta-catenin is a protein with many roles, including helping cells stick together, and regulating gene expression in the Wnt pathway, which is essential for development. Dr. Mei’s previous work has shown that at least in a Petri dish, when a signaling component of the Wnt pathway, called disheveled, is disturbed in muscle cells, it causes problems with their co-cultured neurons. In the early 1900s, German-born Scientist Viktor Hamburger provided some of the first evidence of the importance of retrograde communication in proper development of motor neurons: when he removed the budding limbs of chick embryos, motor neurons decreased in number. “ … (T)he use of transgenic animals has established the importance of muscle ß-catenin in (neuromuscular junction) formation in vivo,” write Drs. Amy K.Y. Fu, Zelda Cheung and Nancy Y. Ip, of Hong Kong University of Science and Technology in an accompanying News and Views. “These findings also underscore the emerging role of Wnt signaling proteins in the regulation of synapse development. The identification of muscle ß-catenin-dependent signals for motoneurons may also contribute to our understanding of neuromuscular disorders, including muscular dystrophy and amyotrophic lateral sclerosis.”

Source: © 2008 Medical College of Georgia

Experiments Support Looking Outside Nerve Cells in ALS

Experiments Support Looking Outside Nerve Cells in ALS
http://www.als-mda.org/research/news/080306nerve_cells.html
Researchers in the laboratory of Don Cleveland at the University of California-San Diego have further extended the suspected role of astrocytes, a type of nervous-system “support” cell, in amyotrophic lateral sclerosis (ALS).
The research team, which included MDA grantee Severine Boillee at UCSD and published its findings online Feb. 3 in Nature Neuroscience, found that diminishing production of a toxic protein in these support cells alone sharply slowed disease progression in ALS-affected mice, even when its production remained high in nerve cells.
When production of the toxic protein in astrocytes was high, the disease progressed more rapidly, and neighboring cells called microglia revved up their production of additional toxic compounds.
The toxic protein in astrocytes in these experiments was abnormal SOD1, a protein made from mutated SOD1 genes, a known cause of genetic ALS.
Until recently, many experts believed that the muscle-controlling nerve cells called motor neurons, which die and cause paralysis in ALS, were the central problem in the disease, and that mutated SOD1 genes caused ALS by their poisonous effects on motor neurons alone.
However, recent evidence from this set of experiments and many others, including those by investigators at the University of Iowa showing that mutated SOD1 protein in microglial cells causes major problems (see Unexpected Discovery), have made a good case for looking beyond motor neurons alone for causes and treatment targets in ALS.

QUITE POSSIBLEY THE BEST QUOTE I EVER CAME ACROSS

"Stay still, Be quiet, and listen to your heart! Then when it speaks, get up and go where it takes you!"

- Susanna Tamaro

A PICTURE OF ME THAT I NEVER THOUGHT I WOULD SEE

Targeting astrocytes slows disease progression in ALS

The article below was published in April of 2008. What I find interesting and relative to this article as it relates to the treatment offered by Beike is that is has also been shown in the past by numerous researchers world wide is that Umbilical Cord Stem Cell’s also known as Hematopoietic stem cells have the ability to differentiate into astrocytes. In the 1960s, scientists studying rats discovered two regions of the brain that contained dividing cells, which become nerve cells. Despite these reports, many scientists still felt that new nerve cells could not be generated in the adult brain. However as science has advanced the views of many have changed and in 1990s scientists finally began to agreed that the adult brain does contain stem cells that are able to generate the brain's three major cell types—astrocytes and oligodendrocytes, which are non-neuronal cells, and neurons, or nerve cells. The world view of the plasticity of the Umbilical Cord Stem also referred to as an Adult Stem Cell and its ability when properly coaxed to transdifferentiate has changed dramatically since the 1990’s. A number of experiments performed over the years have suggested that certain adult stem cell types are pluripotent; this includes those stem cells taken for the umbilical cord. This ability to differentiate into multiple cell types is called plasticity or transdifferentiation.

FACT: Hematopoietic stem cells may differentiate into: three major types of brain cells (neurons, oligodendrocytes, and astrocytes); skeletal muscle cells; cardiac muscle cells; and liver cells.

February 4, 2008
Targeting astrocytes slows disease progression in ALS

In what the researchers say could be promising news in the quest to find a therapy to slow the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, scientists at the University of California, San Diego (UCSD) School of Medicine have shown that targeting neuronal support cells called astrocytes sharply slows disease progression in mice.
The study, conducted in the laboratory of Don Cleveland, Ph.D., UCSD Professor of Medicine, Neurosciences and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research, will appear in the advance online publication on Nature Neuroscience's website on February 3rd.
“Mutant genes that cause ALS are expressed widely, not just in the motor neurons,” Cleveland explained. “Targeting the partner cells like astrocytes, which live in a synergistic environment with the neuron cells, helps stop the ‘cascade of damage.’ Therapeutically, this is the big news.”

ALS is a progressive disease that attacks the motor neurons, long and complex nerve cells that reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body, which act to control voluntary movement. Degeneration of the motor neurons in ALS leads to progressive loss of muscle control, paralysis and untimely death. Estimated to affect some 30,000 Americans, most people are diagnosed with ALS between the ages of 45 and 65. Typically, ALS patients live only one to five years after initial diagnosis.
In findings published in Science in June 2006, Cleveland and his colleagues showed that in early stages of inherited ALS, small immune cells called microglia are damaged by mutations in the SOD1 protein, and that these immune cells then act to significantly accelerate the degeneration of the motor neurons. The new study demonstrates that much the same thing happens to astrocytes, support cells that are essential to neuronal function, and whose dysfunction is implicated in many diseases. The researchers speculate that the non-neuronal cells play a vital role in nourishing the motor neurons and in scavenging toxins from the cellular environment. As with microglia, the helper role of astrocytes is altered due to mutations in the SOD1 protein.
“We tested what would happen if we removed the mutant gene from astrocytes in mouse models,” said Cleveland . “What happened was it doubled the lifespan of the mouse after the onset of ALS.”
Astrocytes are key components in balancing the neurotransmitter signals that neurons use to communicate. To examine whether mutant SOD1 damage to the astrocytes contributes to disease progression in ALS, researchers in the Cleveland lab used a genetic trick to excise the mutant SOD1 gene, but only in astrocytes. Reduction of the disease-causing mutant SOD1 in astrocytes did not slow disease onset or early disease; however, the late stage of the disease was extended, nearly doubling the normal life expectancy of a mouse with ALS.

“Silencing the mutant gene in the astrocytes not only helps protect the motor neuron, but delays activation of mutant microglia that act to accelerate the progression of ALS,” said Cleveland .
The findings show that mutant astrocytes are likely to be viable targets to slow the rate of disease spread and extend the life of patients with ALS. Cleveland added that this may prove especially important news to researchers in California and elsewhere working with stem cells. “This gives scientists a good idea of what cells should be replaced using stem cell therapy. Astrocytes are very likely much easier to replace than the slow-growing motor neuron.”
Source: The University of California San Diego

HELP W/ TYPING

http://cnt.lakefolks.com/

FOR PEOPLE THAT FATIGUE WHILE TYPING OR FOR THOSE WHO CAN'T TYPE
IT'S A VIRTUAL KEYBOARD THAT IS NOTHING SHORT OF A MIRACLE. IT WORKS WITH A MOUSE. POINT AND CLICK AND TYPE................................

NEU2000 AND LITHIUM

Concurrent administration of Neu2000 and lithium produces marked improvement of motor neuron survival, motor function, and mortality in a mouse model of amyotrophic lateral sclerosis.

http://www.amkorpharma.com/index.php

Shin JH, Cho SI, Lim HR, Lee JK, Lee YA, Noh JS, Joo IS, Kim KW, Gwag BJ.

Department of Pharmacology, Ajou University School of Medicine, Sawon, Korea 442-749.The Fas pathway and oxidative stress mediate neuronal death in stroke and may contribute to neurodegenerative disease. We tested the hypothesis that these two factors synergistically produce spinal motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Levels of reactive oxygen species were increased in motor neurons from ALS mice compared with wild-type mice at age 10 weeks, before symptom onset. The proapoptotic proteins Fas, Fas-associated death domain, caspase 8, and caspase 3 were also elevated. Oral administration of 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid (Neu2000), a potent antioxidant, blocked the increase in reactive oxygen species but only slightly reduced activation of proapoptotic proteins. Administration of lithium carbonate (Li(+)), a mood stabilizer that prevents apoptosis, blocked the apoptosis machinery without preventing oxidative stress. Neu2000 or Li(+) alone significantly enhanced survival time and motor function and together had an additive effect. These findings provide evidence that jointly targeting oxidative stress and Fas-mediated apoptosis can prevent neuronal loss and motor dysfunction in ALS.