http://news.prnewswire.com/ViewContent.aspx?ACCT=109&STORY=/www/story/03-09-2009/0004984875&EDATE=
Please review/double-click, the hyperlink above.
It contains some interesting stuff, to say the least.
Quick excerpt:
"This is the first demonstration of transplanted human neurons synapsing, or making mature structural connections, with the rat motor neurons, something which has not been demonstrated before," said Dr. Karl Johe, Neuralstem's Chief Scientific Officer and a study co-author. "Our earlier work with this ALS model showed that the stem cells delayed onset of the disease and played a neuroprotective role. Now we have clear evidence that they can become an integral part of the rat nervous system that controls the muscles. I would expect these cells to be readily accepted by and integrated into a human nervous system, such as in an ALS or a spinal cord injury patient."
Epidermal growth factor promotes the differentiation of stem cells derived from human umbilical cord blood into neuron-like cells via taurine induction in vitro.
Jin W, Xing YQ, Yang AH.Department of Ophthalmology, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan, Hubei Province, 430060,
People's Republic of China.Results of recent investigations have demonstrated the plasticity of mesenchymal stem cells (MSC) can differentiate into neural lineages. In this study, we explored the experimental condition of differentiation into neuron-like cells or rhodopsin (RHOS)-positive cells induced by epidermal growth factor (EGF) and taurine in vitro and to investigate their biological characteristics. MSC were obtained from umbilical cord blood (UCB) of term deliveries. Cultured cells were treated with Dulbecco's modified Eagle's medium/F12 (pH 7.0-7.2) supplemented with 30 ng/ml EGF. After the third cell passage, the cells were trysinized and analyzed with a flow cytometer using the following monocloned antibodies: CD90, CD29, CD34, CD44, and CD45. Taking another MSC of the third passage, its basal medium was replaced with alpha minimum essential medium supplemented with taurine (50 micromol/L). Cells were cultured for an additional 8-10 d, fixed, and then immunocytochemicall y analyzed. Primary antibodies included the following: neuron-specific enolase (NSE), RHOS, and nestin. In our study, we isolated a cell population derived from UCB, which possesses morphological characteristics similar to those of MSC isolated from bone marrow. In the cytometric analysis, MSC did not present labeling for the hematopoietic line (CD34 and CD45) and were positive for CD29, CD44, and CD90. After induction by taurine, 80.5 +/- 16.2% of the cell population expressed NSE, 36.8 +/- 9.6% expressed RHOS, and 29.6 +/- 9.3% expressed Nestin, while only 7.9 +/- 3.5% expressed NSE in the control group. This study demonstrates that partial MSC induced by taurine and EGF can differentiate into neuron-like cells or RHOS-positive cells in vitro, which may provide a promising therapeutic strategy for the treatment of some forms of retinal degeneration.
Breaking News
New Gene Mutation Discovery by ALS AssociationConsortium is Major Research Breakthrough
(February 26, 2009) -
In one of the most significant breakthroughs in the recent history of ALS research, a consortium of scientists organized and funded by The ALS Association has discovered a new gene, ALS6 (Fused in Sarcoma), responsible for about 5 percent of the cases of inherited ALS. The discovery will provide important clues to the causes of inherited ALS, which accounts for 10 percent of all cases, and sporadic ALS, which occurs in individuals with no family history of the disease and accounts for the other 90 percent of cases diagnosed.
“This is a momentous discovery in furthering our understanding of ALS,” said Lucie Bruijn, Ph.D., senior vice president of Research and Development at The ALS Association. “A new gene provides a new piece of the puzzle we can use to shed light on why ALS develops, and where to focus our efforts on creating new treatments and finding a cure.”
The results of this groundbreaking research are published in the Friday, February 27 issue of the prestigious journal Science. The project was led by Tom Kwiatkowski M.D., Ph.D., at Massachusetts General Hospital, and Robert Brown, M.D., of the University of Massachusetts School of Medicine, and ALS Association-funded researchers Caroline Vance, Ph.D., and Christopher Shaw, M.D., of Kings College in London. The project was supported by a consortium of leading ALS researchers from around the world, formed as part of The Association’s Gene Identification Project. Their success reflects an unprecedented effort to accelerate the search for genetic mutations linked to all forms of ALS.
Dr. Brown noted, “We are particularly delighted because our trans-Atlantic consortium has pursued the chromosome 16 gene for more than six years. The ALS Association has been an all-important partner in this search. This discovery should lead to new cell and animal models of ALS, which will accelerate drug development.”
“Global partnerships between investigators and funding agencies, such as the Motor Neuron Disease Association in the United Kingdom, are crucial to making these kinds of breakthroughs,” Dr. Bruijn commented. “This finding has opened up a whole new avenue of research and has the potential to uncover a common mechanism for most forms of ALS.”
The gene mutations were first identified by Dr. Kwiatkowski and were immediately confirmed by Dr. Vance, who also demonstrated abnormal accumulations of the mutant protein in cells cultured in the laboratory and the motor neurons of people carrying FUS mutations.
The gene, called FUS (“fused in sarcoma”), normally carries out multiple functions within motor neurons. These include regulating how gene messages (called messenger RNAs) are created, modified, and transported in order to build proteins. Some of these same functions also are performed by another gene called TARDPB encoding the protein TDP43, and mutations in the TDP-43 gene were recently linked to ALS as well.
“The fact that these two genes help perform the same function suggests that problems in this function may be critical in the development of ALS,” Dr. Bruijn said. “More research into exactly how these two genes work could ultimately lead to new treatments that are effective in slowing or stopping the progression of ALS and extending the lives of people with the disease.”
The mutations in the ALS6 gene were identified by detailed genetic sequencing in several families with an inherited form of ALS (familial ALS). Normally, the ALS6 protein works in the cell’s nucleus, but the mutations caused it to instead cluster outside the nucleus. Further work will be needed to determine precisely how this leads to ALS. With the gene in hand, scientists will be able to create cell and animal models containing the mutated gene, to examine in detail how the mutation operates and how it causes ALS.
“This suggests there may be a common mechanism underlying motor neuron degeneration,” according to Dr. Shaw. Motor neurons are nerve cells in the brain and spinal cord that control muscles. Motor neurons degenerate in ALS.
This is the second ALS-causing gene to be discovered in the past 12 months. SOD1, discovered in 1993, accounts for 20 percent of inherited cases of the disease. Mutations in the TARDP gene account for another four to five percent. The only well-defined causes of ALS are genetic. In both inherited and sporadic ALS, the disease symptoms and pathology are the same.
The possibility that ALS may be caused by several factors is the rationale for The Association’s policy of funding multiple genetic projects around the world and encouraging these leading geneticists to work together and share information to help locate disease-linked genes for faster, more accurate scientific results. By funding research on a global level, The Association helps put together “genetic pieces” of the ALS puzzle.
“Through our support of research such as this study, The ALS Association is committed to finding the causes of ALS, and using that knowledge to develop a cure as rapidly as possible,” Dr. Bruijn said. “We will build on the discovery of this new gene to carry that effort forward.”
From: alscenter@jhmi.edu To: The ALS Community Date: February 18, 2009Subject: Robert Packard Center ALS News Network
TRIALS OF CELL-BASED THERAPY DON'T COME OUT OF THE BLUE
Some thoughts on Geron's start of stem cell-based therapy for spinal injury.http://www.alscenter.org/news/briefs/090218.cfm Late last month, ALS sufferers' hearts had to quicken at the announcement by=the biotech firm, Geron, hailing the start of clinical trials of a stem cel=-based therapy for new spinal injuries. Though the trial is a Phase I study meant to see if injected cells are safe =or humans, and though its patient subjects have had their very specific spi=al cord injuries only one-to-two weeks, the appearance of an authentic tria= involving potentially therapeutic cells - ones aimed at lessening or preve=ting paralysis - is exciting.What about trying out those cells or similar ones for ALS injuries to the ne=vous system?"Packard researchers in this country and Europe are doing an enormous amount=of work to sort out the many steps necessary to discover which cells to use=one day in ALS patients," says Packard Director Jeffrey Rothstein. "But eve= after that most essential work, after the appropriate cell type stands wel= out from the others, questions remain. "These are not simply safety questions," Rothstein says: Many of our ALS pat=ents would be willing to try a new therapy and fully understand the risks.What needs answering are questions of benefit and of procedure. "How do you =dminister the cells," he asks, "so the risk of getting them is justified by=their potential to relieve the disease or improve quality of life? "The impediments to our progress now are typical of what you'd encounter for=any potential new therapeutic drug," he explains. How many cells are approp=iate to deliver? That's the equivalent of finding the appropriate dose of a drug.What's the best way to distribute the cells throughout the brain and spinal =ord? That is akin to asking how often you give a drug.Do you give the cells through an IV or by direct surgical injection? What ha=pens to cells after we put them in? Do they divide like tumors? Do they die=and cause a scar that would hasten ALS effects? "Those are questions we mu=t first sort out in animals," says Rothstein.And a cell therapy carries its own unique concerns: How do we know that the =good' cells we put into one patient are identical to those we'd culture and=give a patient a year later? Quality assurance issues are well-established =or drugs like penicillin, Rothstein adds, but they have to get worked out f=r every new type of stem cell. The Packard Center has been doing its homework, however - not just for its o=n scientists but for the world's.A DECADE OF GROUNDWORK For almost 10 years, our researchers have been laying the groundwork for pos=ible cell therapy for ALS. Many of their published studies have likely infl=enced the Geron trial-planners. Here are a few:- Packard scientist Doug Kerr was the first to show that an animal model of = paralytic disease could be helped by injections of stem cells. - Packard Director Jeff Rothstein and his team solidified the suspicion that=motor neurons' natural protectors are its neighboring glial cells - that th=y remove harmful toxins as they collect in nervous system tissues under ass=ult. (The cells injected in the Geron study have the potential to become gl=al cells, those widespread nervous system cells in close proximity to motor=neurons.) - Work by Don Cleveland and Jean-Pierre Julien sent researchers scurrying mo=e surely to explore the concept of glial cells as protectors. They revealed=that keeping glia healthy can protect even motor neurons carrying an ALS ge=e. - Nicholas Maragakis and Mahendra Rao showed investigators everywhere how to=isolate, culture and precisely identify glial-restricted precursor (GRP) ce=ls - the broad class of "undeveloped" cells akin to the cell types Geron is=injecting. - Maragakis and Rao demonstrated that GRPs are neuroprotective - both in cul=ures that mimic the nervous system and in live animal models of ALS. Maraga=is and Rothstein have gone on to clarify much of the underlying biology. MORE RECENT WORK Because they specialize in ALS biology, Packard scientists know to target st=m cell and related therapies where they'd potentially do the most good. Las= November, for example, they reported a key step, an animal study in which =hey injected glial-restricted precursors precisely around the cervical spin=l cord home to motor neurons that permit breathing. Paralysis of those neur=ns precipitates death in ALS. The rat ALS models in the study survived significantly longer. Their forelim=s and breathing muscles stayed strong and functional far longer, while moto= neuron loss slowed. "This shows us that targeting cell delivery to critica= spinal areas is certainly worthy of investigating as a therapy for ALS, as=a way to slow specific types of motor neuron loss," says researcher Nichola= Maragakis. Now work needed to inch closer to clinical trials is underway.* * *In the last six months, Maragakis and colleague Hongjun Song have been worki=g at what can only be described as ALS's leading edge: they've begun studyi=g human pluripotent stem cells created from the skin of a patient with fami=ial ALS. One of the few recent, legitimate scientific breakthroughs, the technique in=olves reprogramming the patient's skin cells to behave like stem cells. The= the stem cells are coaxed to become motor neurons. This means that Packard=scientists will be able to study the progress of real ALS disease in real h=man cells, something that was out of reach before. ___________________________________ About The Robert Packard Center for ALS Research at Johns Hopkinswww.alscenter.org Located in Baltimore, the Robert Packard Center for ALS Research at Johns Ho=kins is a worldwide collaboration of scientists aimed at developing therapi=s and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Geh=ig's disease.The Center is the only institution of its kind dedicated solely to the disea=e. Its research is meant to translate rapidly from the lab bench to the cli=ic, largely by eliminating time spent waiting for grants and lowering insti=utional barriers to sharing scientific results.Scientists and clinician members of the Packard Center have moved drugs reli=bly and rapidly from preclinical experiments to human trials. Direct or ind=rect links to international biotech or pharmaceutical companies bring the i=frastructure and experience needed to make promising drugs into therapies.Packard scientists are the first to propose and test a combination approach =o drug therapy, a tactic that has worked for AIDS, cancer and other disease=.ALS is a progressive, disabling neuromuscular disease that causes complete p=ralysis and loss of function - including the ability to eat, speak and brea=he. ALS progresses quickly and is not curable. Most patients die within fiv= years of diagnosis._________________________________________Rebecca BergerResearch Program CoordinatorRobert Packard Center for ALS Research at Johns Hopkins5801 Smith Avenue McAuley Suite 110Baltimore, MD 21209410.735.7678 direct410.735.7680 faxrberger6@jhmi.edu www.alscenter.orgwww.fiesta5K.org****************************************************************************=***Click on the link below to unsubscribemailto:sympa@lists.johnshopkins.edu?subject=unsubscribe%20alscenter&body=3DPLEASE%20SEND%20THIS%20EMAIL%20OUT%20FOR%20UNSUBSCRIBINGPlease follow the instructions below if the above link does not work:Compose an email to: sympa@lists.johnshopkins.eduWith Subject: unsubscribe alscenterNote: 'unsubscribe alscenter' should be on the SUBJECT line, NOT IN THE MESS=GE BODY.To contact the list owner: mailto:alscenter-request@lists.johnshopkins.edu
Dear Brothers and Sisters,
We ( Team IPLEX ) are respectful requesting help from any and all family, friends, & supporters . Please Review attachments I have provided You can... cut and paste certain talking points from the attachments , or you can just cut and paste the entire document -- as is... of course,change the address , name, and salutation's. -- Then utilize the Web link that I have provided, to send your elected representatives (2) senators & ( 1) Congressperson a quick e-mail voicing your support for this (PALS) cause. All we are asking is that they (our elected representatives) look into the shady nature of this matter -- end of story... is that too much to ask?... just looked into the matter, on behalf of terminally ill people? -- Please Take 10-15 minutes and Help, because for PALS, it truly is -- A Race against Time. http://www.visi.com/juan/congress/
http://www.senate.gov/general/contact_information/senators_cfm.cfm
The whole Iplex story significantly highlights the lack of care and concern by institutes such as the FDA. The human factor has been totally removed. The FDA's response has been unbelievable & shameful. They (FDA) are in effect shutting patients out of a drug/therapeutic , that they themselves have already (2006) approved for infants/children. Now, they (FDA) are claiming that it is necessary to shut/turn down all IND applications for IPLEX for reasons that it -- kills people? And get this, all based on unsubstantiated data. A Drug Well-Tolerated by Babies? In plain speak, there is something very fishy going on here. We, (Team IPLEX & supporters) feel that the FDA should be making a more concise data-driven argument, or at least before they start making politically motivated & bogus claims that IPLEX kills people... IPLEX has been supplied to Italian, PALS for over 2 years now, over 100 patients, how many of the 100 have died? Faster by using IPLEX.
Stephen & Barbara Byer parents of Ben Byer (famed, movie producer of the award-winning film "Indestructible" ) explain how their son, Ben, after 14 days of taking the drug (IPLEX ), went from "oatmeal and pudding to a Whoppers ." But was subsequently forced to stop taking the drug (IPLEX) when it was pulled/forced off the market by the terms of a patent lawsuit. We (team IPLEX & supporters) fought too hard in 2008, to get the companies to come to terms, (to make IPLEX available ) to shut up and go away now... .
Bottom line, WHAT DO WE (PALS ) HAVE TO LOSE? -- If our (PALS & supporters) current letter writing campaign, is able to inspire, motivate, and or raise awareness to the plight of PALS. I will definitely feel like --Mission Accomplished!! Even if we aren't able to get the FDA to immediately change, there bogus position, I still feel that victory is just around the corner, this fight will not be over... not by a long shot!! -- unless we give up and accept our fate.
If whatever we're able to accomplish with our current e-mail/ letter writing campaign helps the next generation of PALS dream bigger, work harder and once and for all, finish the work we've started, I'll always believed in my heart that we have made our mark as true champions. But Don't Get Me Wrong, I Want to Win This Thing ASAP... If It's Wrong and or Selfish to Want to Live Longer, well then,... I'm Wrong, & Selfish -- End of Story. PS: We Really Need Your Help
http://www.visi.com/juan/congress/
Thanks ,
Eddie spaghetti) Esparza.
There's Definitely Something Wrong with This Picture
Fiscal year 2008, Actual (not estimated) NIH (National Institute of Health) allocation of spending
DISEASE (NIH)-RESEARCH BUDGET
HIV/AIDS research -- 2.9 billion.
Substance abuse research -- 1.76 2 billion.
Drug abuse (NIDA only) -- 1 billion
Obesity research -- 664 million.
Alcohol research -- 452 million.
Depression research -- 402 million
Tobacco research -- 311 million.
Sexually transmitted diseases 245 million.
Food safety research -- 244 million.
Arthritis 232 million.
Sleep research 225 million.
Multiple sclerosis research 169 million
Parkinson's disease research 152 million.
Youth violent research 115 million.
Pneumonia research 93 million.
Infertility research 73 million.
Crohn's disease research, 51 billion.
ALS research 43 million.
Suicide research -- 39 million
Teenage Pregnancy research 21 million
http://report.nih.gov/rcdc/categories/
ALS - Woefully Under-Funded (NIH) Compared to Other Diseases
MS (multiple sclerosis ) seems to offer a reasonable standard of comparison as it has about the roughly similar incidence as ALS (10,000 new cases per year for MS vs.7000 for ALS). There are approximately 400,000 people in the US living with MS vs. about 30,000 with ALS. Why the difference in prevalence if the diseases have a somewhat similar incidence rate? The major factor is lethality. MS patients live a normal life span while, ALS patients have a much shorter life span. If ALS were not such an effective killer, its prevalence rate would obviously be much higher. It seems reasonable that the two diseases should have nearly equal public funding, since they both occur with the similar frequency, but this is not the case. NIH budgets 169 million on MS research but $43 million on ALS? . It is immoral to base funding on prevalence in the context of similar incidence rates, thereby penalizing ALS patients for the lethality of their disease
The next disease for comparison is Huntington’s disease, another disorder caused by degeneration of brain cells, i.e. neurons, in certain areas of the brain. Its incidence and prevalence rate are much lower than ALS and patients usually live 10-25 years after diagnosis. Yet, this disease has an NIH budget of $51 million versus, $43 million for ALS.
For the, 3rd and final comparison, HIV/AIDS. This illness has a large incidence (85,000) and prevalence (1,100,000) The number of patients who die from this disease each year is only a bit more than twice the number of ALS deaths, yet HIV/AIDS has a research budget of nearly $3 BILLION! vs. $41m for ALS-?
CONCLUSION I: Given its incidence rates and high lethality, ALS is woefully under-funded compared to other diseases or and this may explain, at least in part, why so little has been learned about this disease since Lou Gehrig’s death 65 years ago and why there have been no significant advances in treatment. It does not get the recognition it deserves because its high lethality severely limits the number of Americans who are living with the disease at any one point in time.
RECOMMENDATION I: The NIH budget for ALS research should be immediately increased to $110m or the same amount as MS.
The fact that the low prevalence rate of ALS, is directly due to its high lethality, therefore does not provide any incentive for major pharmaceutical companies to search for a cure. The only drug for ALS, Rilutek, about 15 years old now, extends life only 2-3 months, is used by many patients at high cost, yet the maker of the drug, Aventis, claims that it loses substantial money on Rilutek. MS, in comparison, with its 400,000 prevalence in the US alone, presents significant incentive for drug companies to invest in research. In fact, there are 5 meds that have proven very beneficial and sales are big. Avonex, for example, had close to $1b in sales in the last year. Another drug, Copaxone, may have the greatest potential to alter the course of MS and sales, once the issue of side effects is resolved, should be huge. If we accept the view that it costs the companies $800 m over 10 years to develop and bring to market a successful drug, then about $4 billion has been spent to produce these disease mitigating medications, or $400 m per year, not including current research.
The FDA offers an orphan disease program to provide incentives to companies to invest in research of diseases having a prevalence of fewer than 200,000. The program provides tax incentives and other advantages for only small grants; unfortunately the incentives offered are too small to interest large companies with all their research potential.
Conclusion II: Because of ALS’s high lethality, prevalence will always be low. As a consequence, big pharma will not have the incentive to invest in ALS research and the high tech power of drug companies won’t be harnessed to find new therapeutic agents in the fight against ALS.
Recommendation II: Federal health agencies must provide the incentive to big pharma to invest in ALS research. The FDA Orphan Disease Program must be substantially increased to accomplish this. $80m per year in incentives must be allotted to get major companies interested in working on this research. Funding could include a combination of grants, tax credits and exclusive marketing rights, etc. The grants could be reduced as companies come closer to marketing the new agents.
Under-funding of ALS will not be righted without our ( PALS ) active intervention. I am asking for your help on behalf of both the 35,000+ Americans living with the disease today and the estimated 70,000 that ill die every 10 years , and the 7000 that will die just this year, until a cure is found. ALS has been neglected far too long.
Sincerely,
Edward W. Esparza
(pals since 2005)
"For PALS, the cost of waiting/doing nothing, is simply too high."
