Potential treatment for sporadic ALS has been identified by researchers.

Potential treatment for sporadic ALS has been identified by researchers.

What

Two studies detailing the discovery of a possible new therapeutic route for treating a sporadic variant of amyotrophic lateral sclerosis have been published (ALS). The findings were released as a result of a collaborative research arrangement between the Swiss biotechnology firm GeNeuro Inc. and the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health.

The fact that DNA sequences from old retroviruses, known as human endogenous retroviruses, are now present in the human genome as an uncommon byproduct of hundreds of thousands of years of evolution is noteworthy (HERVs). Reactivation of HERVs has been linked to a number of neurodegenerative illnesses, including ALS, even though most stay dormant.

The first of these studies demonstrates that a particular HERV generates a protein that is present in the cerebrospinal fluid (CSF) of ALS patients. When given to neurons cultured in lab plates, this HERV-K ENV protein is hazardous. A unique breed of mouse that has been genetically engineered to produce HERV-K ENV also exhibits symptoms that are very similar to ALS. When ALS patients’ CSF was added to lab-grown neurons, the cells were harmed. When a synthetic antibody tailored particularly to detect HERV-K ENV was introduced as well to those neurons, the harmful effects were decreased. Together, our results show that the symptoms of certain occurrences of sporadic ALS may result from incorrect HERV-K ENV gene activation.

The researchers investigated whether the immune systems of persons with ALS developed any antibodies after learning that a synthetic antibody to HERV-K ENV would be protective. In the second study, the scientists demonstrate that a group of persons with ALS had blood levels of HERV-K ENV antibodies that were greater than those of healthy donors. In those with ALS, the pattern of antibodies against this viral protein was likewise more complicated. Additionally, there was a link between longer overall survival and greater antibody levels against HERV-K ENV.

Together, these results provide further support for the theory that the HERV-K viral reactivation contributes to the onset of ALS and that an antibody response is protective. These findings further highlight the prospect that ALS patients who also have HERV-K reactivation may benefit from therapy with a synthetic antibody produced against HERV-K-ENV.

The ALS Association, GeNeuro Inc., and the NINDS Division of Intramural Research (NS3130) all provided funding for this project.

Who

Avindra Nath, M.D., NINDS clinical director

If you would like to arrange an interview with Dr. Nath, please contact the NINDS Press Team or call (301) 496-5751.

Articles

Steiner JP et al. “HERV-K envelope in spinal fluid of Amyotrophic Lateral Sclerosis is toxic.” Annals of Neurology. DOI: 10.1002/ana.26452

Garcia-Montojo M at al. “Antibody response to HML-2 may be protective in Amyotrophic Lateral Sclerosis.” Annals of Neurology. DOI: 10.1002/ana.26466

NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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