Program to Study ALS Gene Therapy, Genome Editing Launched at Penn

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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A new program at the University of Pennsylvania will pursue ways to use gene therapy and genome editing to treat amyotrophic lateral sclerosis (ALS).

The Program of Excellence for Motor Neuron Disease, launched by researchers at the Orphan Disease Center (ODC) in the university’s Perelman School of Medicine, will receive its initial funding from philanthropic sources.

“I am convinced that it is time to make a serious effort to treat ALS using gene therapy,” James Wilson, MD, PhD, director of the ODC and its affiliated gene therapy program, said in a press release. “To do so, we will leverage the exciting clinical results that have been achieved in gene therapy for spinal muscular atrophy using our vectors, as well as the robust infrastructure in gene therapy translational research we have at the Orphan Disease Center and Gene Therapy Program at Penn.”

The program will build on research underway at ODC, including a recent discovery Wilson made regarding second-generation gene transfer vehicles, known as vectors. They can transport genes into central nervous system (CNS) cells and have been used in several clinical trials, including ones for spinal muscular atrophy (SMA).

In those trials, the press release said, a single infusion of a vector expressing a non-mutated SMA gene was linked to some restored motor function. The release further noted that all the children involved in the trials are alive, including some who are older than 3.

The genes responsible for ALS and SMA are different, but they affect the same motor neurons that are critical for muscle function. The SMA studies suggest Wilson’s technology could be used as a mechanism for treating ALS.

With those trials in mind, the program will advance in three phases. Researchers will first focus on gene therapy for familial ALS, beginning with patients who have defects in the C9orf72 gene. At the same time, Wilson and his team will assess possible strategies on the expression of genes encoding neuroprotective factors. This approach could benefit more patients, but it involves a higher risk of failure. Last, Wilson will explore genome editing as a potential mechanism to correct mutations in genes such as C9orf72.

A group of six international experts will work as external advisers for the program.

“I am honored to serve as the chair of the advisory committee of the Program of Excellence in Motor Neuron Disease of the Orphan Disease Program at Penn,” said Siddharthan Chandran, PhD, FRCP, who is director of the Centre for Clinical Brain Sciences at the University of Edinburgh. “A greater understanding of the pathogenesis of ALS, together with advances in gene therapy that have come out of Penn, create incredible opportunities to make a difference against this devastating disease.”