From Idea to Investigation: CCTS TL1 Award Fuels Physician’s Research on the Genetic Causes of ALS

Amyotrophic lateral sclerosis, or ALS, is a complex disease to treat and also a difficult one to understand. Summer Gibson, MD, Assistant Professor of Neurology, who has worked with ALS patients for the past six years, since her residency. She says one of the most disappointing things about talking to her patients is that she can’t answer even some of their simplest questions like, “Why does ALS occur?”

It has long been known that ALS causes neuromuscular decline that leads to difficulty moving and breathing, but what triggers the disorder in most patients has remained a mystery. A hope of answering this type of question for patients drove her toward research.

“If you don’t know the simplest parts of the disease, then you can’t move on to understand the more complex parts,” said Gibson, referring to ALS.

Realizing this work would require a different type of training than she had as a physician, she applied to the TL1 scholars program run by the Center for Clinical and Translational Science (CCTS). The one to two-year long program provides training and support for postdoctoral fellows and faculty in the study of genetic disease.

As part of the TL1 scholars program, Gibson worked with Lynn Jorde, PhD, Chair of Human Genetics, and Stefan Pulst, MD, Chair of Neurology, to study the genetic causes of ALS. It has long been known that cases of ALS in patients with a clear family history are caused by genetic mutations. More recently, it has been accepted that some cases in patients with no family history might also be caused by some of the same genes. However, estimates of how many cases are caused by non-familial genetic mutations vary widely. The group wanted to pin down this number to decide where to direct their research to better understand the disease.

The research team, along with MD/PhD student Johnathan Downie, took an approach that others studying ALS haven’t. Not only did they look at the genetic mutations present in patients with ALS, they also used predictive analysis tools to help understand how these gene mutations would affect the proteins they produce.

They found that nearly 1 in 5 cases of ALS in patients without family history are caused by mutations in genes already known to be linked to ALS.

Building off this groundwork, she is now doing animal modeling and studying a new gene she thinks may be linked to familial and non-familial ALS. This new gene could be the key to illuminating an entirely new pathway for the disease.

She credits the TL1 scholars program with giving her the training and focus she needed to fuel her ongoing research. The impact of her research goes even beyond the results of her studies. The project has connected her with other institutions and allowed her to build relationships that could lead to larger consortium studies.

Even though it may be years or decades before she will be able to explain to all her patients what cause their disease, she feels her training has already had positive impacts.

“The clinic benefits because the patients now get to be involved in clinical trials,” she says. “And my patients benefit because I have more knowledge I can use to treat them.”