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Gene Therapy Strategies for Amyotrophic Lateral Sclerosis

Dr. Chris Mueller and Dr. Mail Elmallah from the Horae Gene Therapy Center are conducting research and developing therapeutic strategies for rare inherited diseases such as the Amyotrophic Lateral Sclerosis (ALS).


What is Amyotrophic Lateral Sclerosis (ALS)?

Amyotrophic lateral sclerosis (ALS), also known as Charcot disease after the physician who first described it, and Lou Gehrig’s disease in the US after a famous baseball player who suffered from ALS, is a neurodegenerative disorder that primarily affects the motor neurons.

Clinically this leads to progressive muscle weakness, progressive paralysis and ultimately death within three to five years post-diagnosis. There is currently no cure for ALS. Despite the number of ongoing clinical trials, the only FDA-approved treatment to date is riluzole, which only increases patient survival by about 3 months. There is therefore an unmet medical need for this fatal disease, and several novel therapeutics are being actively investigated. One of the proposed strategies is gene therapy.


Dr. Robert Brown, D.Phil, MD

A leading researcher for Amyotrophic Lateral Sclerosis (ALS)

Robert Brown received a D.Phil. degree in Neurophysiology from Oxford University and M.D. degree from Harvard University. Dr. Brown completed his residency at Massachusetts General Hospital/Harvard Medical School and research fellowship at Boston Children’s Hospital, where he expanded his research in identifying gene defects that underlie ALS and related neuromuscular disorders. He was a lead member of the team identifying the first ALS gene (SOD1) and has subsequently identified others, including alsin, dynactin, FUS/TLS, ErbB4 and profilin1. He has also identified causative gene defects in other disorders including limb girdle dystrophy type 2B, hereditary sensory neuropathy, and hyperkalemic paralysis. 

He has published more than 250 peer-reviewed reports and 60 reviews and chapters on these topics. Dr. Brown is also well known for his work with patient advocacy groups and charitable organizations. He is a founding member of the Northeast ALS Study Consortium and president of the ALS Therapy Alliance's Board of Directors. Dr. Brown is a member of the American Neurological Association, has been inducted into the Institute of Medicine and 2011, named a member of the Association of American Physicians.

Dr. Robert Brown is conducting research and developing therapeutic strategies for rare inherited diseases such as the Amyotrophic lateral sclerosis (ALS)

Robert Brown, D.Phil, MD

LaChance Family Chair of Neurology, Director, ALS Clinic, Co-Director, Laboratory for ALS Genetics, Co-Director, Neurotherapeutics Institute

Visit Profile Page Contact Dr. Brown 



Dr. Chris Mueller, PhD

A leading researcher for Amyotrophic Lateral Sclerosis (ALS)

Chris Mueller, PhD, is an Associate Professor of Pediatrics and a faculty member of the Horae Gene Therapy Center. Dr. Mueller received his PhD from the University of Florida and later became an independent investigator at UMass where he established his lab in 2011. Alpha-one antitrypsin has always remained his primary line of research. Dr. Mueller was recently awarded the 2016 Shillelagh Award from the Alpha-1 Foundation, which rewards outstanding Alpha-1 researchers and clinicians. 

Dr. Mueller's gene therapy strategy on Amyotrophic Lateral Sclerosis (ALS)

SOD1-linked ALS program

This is our more advanced program. We have developed a vector that efficiently silences the SOD1 gene. After establishing proof-of-concept in ALS mice, in the SOD1G93A model, we demonstrated safety and efficacy in non-human primates (you can see all our results here). We are now doing a long-term safety study in non-human primates.

The next step for us is a compassionate use human trial. In parallel, we are starting a canine clinical trial. SOD1-linked ALS is a naturally occurring disease in dogs. 

C9ORF72-linked ALS program

The program is in preclinical development. We have developed various silencing vectors and demonstrated their efficacy in neurons (read more about the study here). We are currently establishing proof-of-concept in ALS mice, in two proprietary C9ORF72 models.

In parallel, we have developed CRISPR-based gene editing constructs, and we are currently establishing proof-of-concept in the same murine models.

Other research interests

Currently Dr. Mueller is also developing gene therapy strategies on Alpha-one Antitrypsin (AAT) DeficiencyCystic Fibrosis and Huntington's Disease.


Dr. Mueller has recenlty developed a gene silencing therapy

with Dr. Robert Brown, a world leader in the field of ALS.

They are completing preclinical studies!


Dr. Chris Mueller from the Mueller Lab (Horae Gene Therapy Center) is conducting research and developing therapeutic strategies for rare inherited diseases such as the Amyotrophic lateral sclerosis (ALS)

Chris Mueller, PhD

Associate Professor, Department of Pediatrics and Horae Gene Therapy Center

View Publications Visit Lab Website