[BillO]

The ALS Community Date: February 18, 2009
Subject: Robert Packard Center ALS News Network TRIALS OF CELL-BASED THERAPY DON'T COME OUT OF THE BLUESome 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 cell-based therapy for new spinal injuries. Though the trial is a Phase I study meant to see if injected cells are safe for humans, and though its patient subjects have had their very specific spinal cord injuries only one-to-two weeks, the appearance of an authentic trial involving potentially therapeutic cells - ones aimed at lessening or preventing paralysis - is exciting. What about trying out those cells or similar ones for ALS injuries to the nervous 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 even after that most essential work, after the appropriate cell type stands well out from the others, questions remain. "These are not simply safety questions," Rothstein says: Many of our ALS patients 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 administer 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 appropriate 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 cord? 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 happens 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 must 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 for drugs like penicillin, Rothstein adds, but they have to get worked out for every new type of stem cell. The Packard Center has been doing its homework, however - not just for its own scientists but for the world's. A DECADE OF GROUNDWORK For almost 10 years, our researchers have been laying the groundwork for possible cell therapy for ALS. Many of their published studies have likely influenced the Geron trial-planners. Here are a few: - Packard scientist Doug Kerr was the first to show that an animal model of a 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 they remove harmful toxins as they collect in nervous system tissues under assault. (The cells injected in the Geron study have the potential to become glial cells, those widespread nervous system cells in close proximity to motor neurons.) - Work by Don Cleveland and Jean-Pierre Julien sent researchers scurrying more surely to explore the concept of glial cells as protectors. They revealed that keeping glia healthy can protect even motor neurons carrying an ALS gene. - Nicholas Maragakis and Mahendra Rao showed investigators everywhere how to isolate, culture and precisely identify glial-restricted precursor (GRP) cells - the broad class of "undeveloped" cells akin to the cell types Geron is injecting. - Maragakis and Rao demonstrated that GRPs are neuroprotective - both in cultures that mimic the nervous system and in live animal models of ALS. Maragakis 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 stem cell and related therapies where they'd potentially do the most good. Last November, for example, they reported a key step, an animal study in which they injected glial-restricted precursors precisely around the cervical spinal cord home to motor neurons that permit breathing. Paralysis of those neurons precipitates death in ALS. The rat ALS models in the study survived significantly longer. Their forelimbs and breathing muscles stayed strong and functional far longer, while motor neuron loss slowed. "This shows us that targeting cell delivery to critical 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 Nicholas Maragakis. Now work needed to inch closer to clinical trials is underway. * * * In the last six months, Maragakis and colleague Hongjun Song have been working at what can only be described as ALS's leading edge: they've begun studying human pluripotent stem cells created from the skin of a patient with familial ALS. One of the few recent, legitimate scientific breakthroughs, the technique involves reprogramming the patient's skin cells to behave like stem cells. Then 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 human 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 Hopkins is a worldwide collaboration of scientists aimed at developing therapies and a cure for amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The Center is the only institution of its kind dedicated solely to the disease. Its research is meant to translate rapidly from the lab bench to the clinic, largely by eliminating time spent waiting for grants and lowering institutional barriers to sharing scientific results. Scientists and clinician members of the Packard Center have moved drugs reliably and rapidly from preclinical experiments to human trials. Direct or indirect links to international biotech or pharmaceutical companies bring the infrastructure and experience needed to make promising drugs into therapies. Packard scientists are the first to propose and test a combination approach to drug therapy, a tactic that has worked for AIDS, cancer and other diseases. ALS is a progressive, disabling neuromuscular disease that causes complete paralysis and loss of function - including the ability to eat, speak and breathe. ALS progresses quickly and is not curable. Most patients die within five 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