The ALS challenge continues

HSCI scientists are using stem cells to redefine what it means to study this deadly disease

Professor Kevin Eggan was mid-sentence, discussing the importance of raising awareness for ALS research, when members of his lab dumped five buckets of freezing water over his head. Eggan recovered, gave the camera crew a smile and, soaking wet, nominated Howard Hughes Medical Institute President Robert Tjian, long-time collaborator Christopher Henderson at Columbia Medical Center, and Harvard biochemist Adam Cohen to do the same

It was only a matter of time before Eggan did an ALS Ice Bucket Challenge video. The viral fundraising/awareness campaign has brought in over $100 million for the ALS Association, which is a regular supporter of the Eggan Lab.

Harvard President Drew Faust also took part and was doused by Eggan in honor of a friend she recently lost to the disease. “We have a long way to go,” she said, as the members of the Eggan Lab looked on in the background. “But the people who are behind me today are testimony that we are making real progress.”

For years, HSCI researchers have been exploring new platforms to illuminate the complexities of neurodegenerative diseases like ALS, short for amyotrophic lateral sclerosis. These platforms have not only made clear how the disease destroys a person’s motor neurons, but have revealed new strategies for slowing cell death.

In 2008, Professor Eggan first raised the possibility of growing ALS patient-derived stem cells in a laboratory dish. At that time, there was no way to directly access and study living human tissue with the disease. Patient-grown stem cells have since allowed scientists to explore how specific mutations cause the disease and screen for drugs that might fix these problems. This year, the Eggan Lab reported two major findings as a result of their work.

First, there is a direct link between a group of inflammatory molecules, called prostanoids, and the damage to motor neurons done by ALS. By removing prostanoid receptors in glial cells—the background cells of the nervous system—it is possible to slow the progression of the disease. In mouse models, this increased survival time by 5-10 percent.

Second, Professor Eggan, working with Dr. Clifford Woolf at Boston Children’s Hospital, found that many of the mutations that cause ALS may be linked by an ability to trigger abnormally high excitability in motor neurons, so that they send electrical signals more readily. The research team then conducted studies of the anti-epilepsy medication, retigabine, on patient neurons in a dish and found that it reduced the hyperexcitability of the cells.

All eyes are now on an ongoing Phase I clinical trial of this epilepsy drug at Massachusetts General Hospital, which could prove that patient stem cells are the path forward for finding new therapies for ALS and other diseases.