“Neuron replacement is the future–but astrocyte replacement can be done now”
Those were the words of stem cell biologist Clive Svendsen during his plenary lecture at the American Academy of Neurology’s annual meeting in Toronto April 15. Svendsen won this year’s Sheila Essey award, which honours scientists whose research has significantly contributed to understanding, preventing and curing amyotrophic lateral sclerosis (ALS).
ALS kills motor neurons in the brain and spinal cord causing progressive paralysis and death. Efforts to stop or even slow the degeneration with drugs have had little success; so replacing the dying neurons is a plausible alternative. But the idea is fraught with challenges, such as how to deliver cells into motor areas throughout the nervous system and, once they’re in the right place, how to get their axons to connect to targets up to a metre away.
But Svendsen thinks a different cell-replacement strategy could slow ALS progression until neuron replacement is possible. In a 2007 study published in PLoS One, Svendsen and his team at the University of Wisconsin-Madison showed that neural stem cells engineered to release growth factor transplanted into the spinal cord of a rat model of ALS migrated to degenerating areas and protected motor neurons. The cells became astrocytes—a type of support cell. But the growth factor-pumping cells didn’t stave off paralysis, prompting the group to look for ways to keep the surviving motor neurons connected to their muscle targets. In a 2008 study published in Molecular Therapies, the group transplanted the same cells into rats’ spinal cords and muscles. Not only did the motor neurons survive and stay connected to the muscles longer, disease progression was delayed and survival was prolonged.
Now at Cedars-Sinai Regenerative Medicine Institute in Los Angeles, Svendsen is in the process of taking his astrocyte replacement treatment into clinical trials. But the process is tedious. He first has to amass a bank of cells that have been isolated using appropriate culture medium and programmed to pump out the growth factor by a clinical-grade lentivirus. Then he has to transplant those same cells into animal models to show they’re safe (not tumor-forming) and effective. And once the cells are just right, he has to show he can safely deliver them into human nervous tissue—a feat he plans to accomplish with a minimally invasive lumbar puncture.
The first U.S. FDA-approved trial of stem cell transplantation in ALS began in January 2010 at Emory University in Atlanta. Two patients have had multiple injections in their lumbar spinal cords, the area that controls leg movement. The phase I trial will only assess the safety of the cells and the injection, not the effects on disease progression. But patients are urged to wait for the effectiveness of stem cell treatments to be determined by properly controlled clinical trials—an April 22 episode of 60 Minutes exposed a team of medical con men in Mexico charging hopeful ALS patients $47,000 for bogus transplants. Svendsen hopes to have transplant-grade cells ready this summer.
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