The routine activities of daily life that so many of us take for granted—eating a meal, taking a walk, answering the telephone—all depend on healthy, fully functioning motor neurons, the nerve cells in the spinal cord that make it possible to control our muscles.
In diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease), the motor neurons are either unable to, or have lost the ability to, carry out this vital role. Since there is no treatment or cure for SMA, which affects infants and young children, or ALS, which strikes adults, afflicted patients become progressively weaker and, with some exceptions, die prematurely.
Through its new, large-scale core facility, the Therapeutic Screening Center (TSC), HSCI is providing a ray of hope for patients with motor neuron diseases. Led by Lee Rubin, PhD, the TSC’s unique combination of specialized scientific expertise and state-of-the-art technologies is expediting research aimed at identifying smallmolecule compounds that could potentially be developed into drugs to treat, or perhaps even cure, patients suffering from motor neuron diseases.
The TSC’s work in this area is greatly enhanced by its ability to generate billions of motor neurons a week from embryonic stem cells—including disease-specific embryonic stem cells derived from mouse models—for screening. “This allows us to screen for effective therapeutics in the specific neuronal cell type affected by these diseases. Until now, this has not been feasible,” explains Rubin.
In recognition of HSCI’s ability to rapidly move research from bench to bedside, the SMA Foundation and the ALS Association recently awarded grants to fund TSC-based work, the ultimate goal of which is to find treatments or cures for these diseases as quickly as possible.
The SMA Foundation grant is being used to fund research using disease-specific motor neurons from mouse embryonic stem cells to identify agents that increase the expression of a vital protein, SMN, that is deficient in patients with SMA, and to understand the underlying biology of the disease. SMN protein is produced by every cell in the body, but only motor neurons are uniquely dependent on critical levels of this protein for their survival.
The ALS Association grant is part of the organization’s TREAT ALS (Translational Research Advancing Therapy for ALS) initiative, a program to accelerate the discovery and testing of new treatments for ALS. With this funding, the TSC will develop a rapid, automated technique to screen small-molecule candidates that might eventually be developed into drugs to slow or halt the progression of ALS. This work will rely, in part, on motor neurons derived from mouse embryonic stem cells that are generated in the lab of HSCI Principal Faculty member Kevin Eggan, PhD.
“The support of both the SMA Foundation and the ALS Association is helping make it possible for us to produce cell populations that are otherwise inaccessible,” says TSC head Rubin. “This gives us the unique ability to identify and develop therapeutics for patients suffering from these and other devastating neurodegenerative diseases.”