Patient stem cells help identify common problem in ALS

PUBLIC RELEASE DATE:

3-Apr-2014

Contact: B.D. Colen bd_colen@harvard.edu 617-413-1224 Harvard University

Harvard stem cell scientists have discovered that a recently approved medication for epilepsy may possibly be a meaningful treatment for amyotrophic lateral sclerosis (ALS)Lou Gehrig's disease, a uniformly fatal neurodegenerative disorder. The researchers are now collaborating with Massachusetts General Hospital to design an initial clinical trial testing the safety of the treatment in ALS patients.

The investigators all caution that a great deal needs to be done to assure the safety and efficacy of the treatment in ALS patients, before physicians should start offering it.

The work, laid out in two related papers in the April 3 online editions of Cell Stem Cell and Cell Reports, is the long-term fruition of studies by Harvard Stem Cell Institute (HSCI) Principal Faculty member Kevin Eggan, PhD, who, in a 2008 Science paper, first raised the possibility of using ALS patient-derived stem cells to better understand the disease and identify therapeutic targets for new drugs.

Now Eggan and HSCI colleague Clifford Woolf, MD, PhD, have found that the many independent mutations that cause ALS may be linked by their ability to trigger abnormally high activity in motor neurons. Using neurons derived from stem cells made from ALS patient skin cells, the two research teams conducted clinical trials of the anti-epilepsy medication on neurons in laboratory dishes, finding that it reduced the hyperexcitability of the cells.

ALS is a devastating and currently untreatable degradation of motor neurons, the long nerve cells that connect the spinal cord to the muscles of the body. While several potential treatments have looked promising in mice, all proved disappointing in the clinic.

"The big problem in ALS is that there are more than a hundred mutations in dozens of genes that all cause the disease, but almost all of the therapeutics that have gone forward in the clinic have done so for just one of those mutations, SOD1, which almost everyone studies in mice," said Eggan, a professor in Harvard's Department of Stem and Regenerative Biology.

"And so," he continued, "the key question that we really wanted to address wasare clinical efforts failing because the mouse is taking us on a wild goose chase, or is it simply that people haven't had the opportunity to pre-test whether their ideas are true across lots of forms of ALS?"

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Patient stem cells help identify common problem in ALS