Some forms of amyotrophic lateral sclerosis (ALS) could actually be caused by an infectious virus, with scientists reporting that human endogenous retrovirus-K (HERV-K), normally dormant, has been found in an active form in the postmortem brain cells of certain individuals with ALS.
Experiments using the active HERV-K in cells grown in a dish and in mice with experimental ALS further demonstrated that the virus kills cells in a manner similar to what is observed in ALS. The findings, considered important, inspired the launch of a small clinical trial examining the use of combination antiretroviral therapy in people with sporadic ALS.
The researchers, led by Avindra Nath, MD, reported the series of experiments in the September 30 issue of Science Translational Medicine, in an article titled “Human endogenous retrovirus-K contributes to motor neuron disease.“ Nath is clinical director of the National Institute of Neurological Disorders and Stroke (NINDS) and chief of the NINDS section of infections of the nervous system.
In ALS (also known as Lou Gehrig’s Disease), nerve cells that control movement progressively die in the brain and spinal cord. This causes muscle weakness, paralysis, and eventually loss of breathing and death. Sporadic ALS accounts for approximately 90–95% of all ALS. Unlike inherited forms, sporadic ALS can affect anyone.
“We have a clinical trial in place for enrolling 10 patients to give them a combination of four antiretroviral drugs to see what happens to HERV-K,” stated Dr. Nath, in an interview with the journal Neurology Today. Antiretroviral medications are already approved and commonly prescribed for use in human immunodeficiency virus (HIV) treatment. Dr. Nath added, “We have unpublished data showing that they do have an effect [in ALS], but not as strong as they have on HIV. When you treat HIV, if you don’t get the virus down close to zero, it has no effect on the disease clinically. We want to see in the pilot clinical trial if combination antiretroviral therapy makes any difference to the HERV-K virus in vivo.”
The researchers emphasized that while the antiretroviral treatment is showing promise and ALS patients are starting to request it, clinical trials are needed to more fully understand the medications and their effectiveness. ALS patients should not take antiretroviral medications outside of clinical trials, Dr. Nath and others said.
Hiroshi Mitsumoto, MD, FAAN, the Wesley J. Howe professor of neurology and director of the MDA/ALS Center at Columbia University Medical Center, also feels the study will be of importance if its results can be replicated in future studies like the pilot trial.
Further work is also needed to determine which forms of ALS may be involved, he said. “Almost everyone agrees it [ALS] is made up of different diseases, and that the symptoms are different from case to case. Probably the causes are different from case to case, so this endogenous retrovirus might be the cause of only some cases. It might be an important cause, but we can’t be sure of that yet,” Dr. Mitsumoto said.
Hopefully the trial will prove that antiretroviral treatments are effective for some forms of ALS, and the research can advance to larger trials. ALS is currently incurable, and therapies to halt or slow the disease are greatly needed.