Amyotrophic Lateral Sclerosis Research
at MassGeneral Institute for Neurodegenerative Disease
The Amyotrophic Lateral Sclerosis (ALS) program includes genetic research, molecular research, drug discovery, animal studies, and human clinical trials of potential new therapies. This research is complemented and coordinated with a large, multidisciplinary outpatient practice staffed with ALS specialists- physicians, nurses, and therapists. MIND’s ALS research effort is led by Dr. Merit Cudkowicz, who has worked in the field for more than 15 years and directs both the Mass General Neurological Clinical Research Institute and the Northeast ALS Consortium.
The cause of the majority of ALS is still a mystery. However, 10% of people with ALS inherit the illness (“familial”). Studying these families where ALS is very common has been essential to making research breakthroughs. Mass General’s genetics team lead by Dr. Robert Brown discovered the first ALS gene, superoxide dismutase (SOD1) in 1993, which led to the creation of mouse model of ALS in 1994. After the first ALS gene mutation (SOD 1) was found, several other gene defects have been found that can cause ALS in particular families, most recently the FUS/TLS gene, discovered at MIND. Each gene discovery catalyzes an explosion in research, as scientists around the world study the gene’s role in nerve cell function.
Basic Science - Clues About ALS
By studying the molecules and proteins that are modified in brain cells affected by ALS, researchers at MIND hope to identify the most logical targets for potential treatments. Laboratories at MIND have been at the forefront of research that describes the molecular events preceding and during the destruction of motor neurons throughout the relentless progression of ALS.
One major area of study is to characterize the motor neuron cell death process that is triggered by the mutant SOD1 protein in ALS. Studies have shown that the protein activates a series of “suicide genes” that mistakenly tell the cell to stop functioning and die. While SOD1 is typically thought to be involved in inherited cases of ALS, MIND investigators are examining its role in sporadic ALS in humans and mice.
Michele Maxwell, PhD is examining the possibilities of using a cutting edge technique called RNA interference as a way to understand ALS and mimic the effects of potential therapeutics. RNA is the material that translates the gene and encodes SOD1 protein. By turning off or interfering with SOD1 RNA, scientists can prevent the production of defective proteins that lead to disease. She will also be able to see, in real time, how shutting off SOD1 changes the biological functioning of the mouse’s brain.
As we develop drugs for diseases like ALS that were previously considered untreatable, it becomes essential to find ways to easily diagnose disease at its earliest stage as well as assess whether new drugs are having the intended effect. MIND scientists are seeking biomarkers – blood, fluid or brain measurements– that will provide important information about the progression of ALS and allow us to measure changes over time and in response to therapy. Patients contribute to this effort by donating blood and spinal fluid so that researchers can look for genes, metabolites and other markers of disease. They will compare ALS patients with healthy adults, those with pure lower or upper motor neuron diseases, as well as other neurological diseases that may mimic motor neuron disease. Through comparison of these samples, the researchers hope to learn more about the underlying cause of ALS and find unique biological markers that could help develop new therapies.
At MIND, discoveries in the laboratory have immediate implications for development of potential therapeutics. Scientists aggressively pursue any idea that emerges to see if there are existing drugs that could modify the disease.
To find completely novel compounds, MIND houses a high-throughput drug screening laboratory that collaborates with our ALS scientists on drug discovery projects, and allows researchers to test their ideas with compounds that may slow or halt disease progression. Dr. Alex Kazantsev is head of this drug development lab, and works closely with Michelle Maxwell’s laboratory.
Through collaborations with the National Institutes of Health, Harvard Medical School, Johns Hopkins University, Thomas Jefferson University and other institutions, assays from the MIND’s laboratories are now being used to screen hundreds of thousands of compounds. Our hope is that through sharing and collaboration we will gain access to the one or two compounds out of a million that can eventually be developed into effective treatment for ALS.
MIND houses an animal laboratory that allows researchers to test promising drugs in mouse models of ALS, looking for drugs that delay the onset of the disease or improve survival. The close collaboration with ALS clinicians at the Neurological Clinical Research Institute allows us to quickly translate findings in ALS mouse studies into human trials.
The Mass General Neurological Clinical Research Institute (NCRI) rapidly brings new advances from the laboratory into testing in people with ALS and other neurodegenerative disorders. The NCRI is comprised of over 20 clinical researchers who are experienced in clinical trial design and conduct for ALS and other neurodegenerative disorders.
Dr. Cudkowicz also co-founded the Northeast ALS Consortium (NEALS), an organization of ALS scientists and clinical researchers from over 70 academic institutions from all over the country that was formed to quickly and efficiently launch multi-center therapy trials in ALS. Dr. Cudkowicz is the Co-Director of NEALS and the Mass General NCRI acts as the Coordination, Data Management and Biostatistics Center for NEALS. Please click about ongoing clinical trials in ALS.
Clinical trials are coordinated with the comprehensive patient care provided at the Mass General ALS Clinic. The Clinic offers a multidisciplinary team approach to treating ALS and supporting patients and their families. It also provides second opinions and diagnostic testing to confirm an ALS diagnosis. Find information about clinical studies on the Clinical Trials page within the Mass General Neurology ALS Clinic site, on the Neurology Clinical Trials pages, or on the ALS Consortium website.