The California Institute for Regenerative Medicine has awarded a team led by Michael Snyder, PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics, a $13 million grant to investigate the genetic causes of amyotrophic lateral sclerosis, a debilitating and fatal disease with no cure.

In ALS, also known as Lou Gehrig’s disease, motor neurons gradually die, leading to muscle weakness and, eventually, paralysis. Some cases of ALS are caused by a single genetic mutation. However, in most people, the disease is likely caused by a complex blend of multiple genes plus environmental factors, Snyder said.

The research team is taking advantage of recent advances in artificial intelligence to find genes and other regions of DNA that contribute to ALS.

“I’m excited because we’re putting together a wonderful combination of new AI-based approaches that just weren’t possible a year ago — and a great team, with experts in various fields — to take on a tough problem,” said Snyder, the project’s principal investigator.

Snyder and his colleagues will use their new method to look for genes and regulatory regions of DNA that are different in people with and without ALS. They’re zooming in on particular cell types: not only motor neurons, but also other types of brain cells. In different kinds of cells, different genes may contribute to the disease. The researchers will check their findings in a cell model of ALS to see if they can change the signs of the disease by altering the genes.

The team has already used this method to identify one gene that wasn’t previously known to be associated with ALS. Snyder hopes to find many, many more.

“You don’t want to put all your eggs in one basket; you want to find more genes like this,” he said.

Snyder and his colleagues expect to give scientists working on ALS treatments much more information to work with and new targets to go after. The team will share its findings publicly so that other researchers can follow up and advance the science further.