Tuesday, April 29, 2008
ANOTHER DAY OF ME MAD AS HELL
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.
Friday, April 25, 2008
Thursday, April 24, 2008
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!
Monday, April 21, 2008
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.
Sunday, April 20, 2008
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
Friday, April 18, 2008
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.
Thursday, April 17, 2008
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 email@example.com. For more information about Kyowa Hakko visit www.kyowa-usa.com.
Monday, April 14, 2008
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."
Sunday, April 13, 2008
Saturday, April 12, 2008
Good news for Motor Neuron Disease sufferers
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.
Friday, April 11, 2008
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)
Thursday, April 10, 2008
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/
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
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."
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.
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?
Wednesday, April 9, 2008
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.
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.
Tuesday, April 8, 2008
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. __________________
Monday, April 7, 2008
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.
Saturday, April 5, 2008
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;
Friday, April 4, 2008
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
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.
Thursday, April 3, 2008
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
Wednesday, April 2, 2008
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................................
Tuesday, April 1, 2008
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.