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Study Shows Drug Lowers Levels of Biomarker Linked to ALS

Decades-Old Drug Used to Treat Malaria Targets Genetic Mutation in ALS Patients

New York, NY—June 12, 2017

A new study finds that a decades-old drug used to treat malaria lowers levels of a biomarker linked to the inherited form of amyotrophic lateral sclerosis, also known as ALS and Lou Gehrig's Disease. The research, conducted by investigators at Hospital for Special Surgery and other centers, was published online in the Annals of Neurology, in advance of the June print edition of the journal.

Some people with the inherited form of ALS have a mutation in the SOD1 gene. Researchers set out to determine if pyrimethamine, a drug that has been around for decades, could safely and effectively lower levels of the toxic protein produced by the gene mutation.

"Our multi-center international study found that pyrimethamine reduced levels of SOD1 in the cerebrospinal fluid of patients with familial ALS, and the amount of lowering was related to the dose of pyrimethamine," noted Dale J. Lange, MD, principal investigator and neurologist-in-chief at HSS. "There is currently no cure for this devastating disease, but our study represents the first time a drug lowered a protein known to be relevant to disease progression; as such, a slowing of disease progression would be expected."

Amyotrophic lateral sclerosis is a relentless disease that progressively attacks nerve cells in the brain and the spinal cord. As time goes on, patients lose the ability to initiate and control muscle movement, their speech is affected and they become paralyzed. Swallowing and breathing become increasingly difficult, and ALS is often fatal within three to five years. In addition to Lou Gehrig, acclaimed physicist Steven Hawkings is a well-known person with ALS.

The study, supported by a grant from the Muscular Dystrophy Association of America, enrolled 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. Out of the patients enrolled, 24 completed six visits over 18 weeks, and 21 completed all study visits.

The researchers noted that their study represents the largest prospective clinical and biological investigation of patients with familial ALS in the literature to date. "To our knowledge, this is the first study in humans with ALS that targeted and achieved a significant reduction of a disease-relevant biomarker in the cerebrospinal fluid. We found that pyrimethamine was safe and well tolerated in patients with ALS caused by different SOD1 mutations," Dr. Lange noted.

"Although not proven by this study, a slowing of disease progression was observed. A larger study is needed, and is being planned, to determine if pyrimethamine does indeed influence the disease course in ALS patients."

 No significant change in quality of life was observed over the nine-month study period. Study limitations included the fact that patients had varying levels of disease severity, and those with the worst symptoms were more likely to drop out, according to the investigators.


About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic on musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.


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