From: alscenter@jhmi.edu

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