'Junk DNA' virus may contribute to ALS

By John Murphy, MDLinx
Published January 21, 2016

Key Takeaways

Researchers found evidence that a dormant retrovirus was active in some patients with amyotrophic lateral sclerosis (ALS), causing neuronal damage and contributing to pathogenesis of the disease. This discovery raises the hope that blocking the virus with antiretroviral drugs, similar to those used to suppress HIV, may help some ALS patients.

This investigation was prompted by a single case more than 10 years ago.

“I came across a patient who had HIV infection and also developed symptoms of ALS,” said Avindra Nath, MD, whose research involves how HIV affects the brain. He is clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study. “Once we treated that patient [with antiretroviral drugs] for the HIV infection, the ALS got better. That made us wonder: Is it possible that there may be some retrovirus involved in ALS itself?”

More than 8% of human DNA is made up of human endogenous retroviruses (HERVs). These retroviral sequences are remnants of infections that occurred over several million years, resulting in the integration of provirus genomes into human DNA. But, in time, mutations rendered most of these retroviruses defective.

“People call the genes for these viruses junk DNA,” Dr. Nath said. “Our results suggest they may become activated during ALS.” The researchers' findings were published online September 30, 2015 inScience Translational Medicine.

In this study, Dr. Nath and colleagues found evidence of the human endogenous retrovirus K (HERV-K) in autopsied brains of patients with ALS, but HERV-K was not found in brains of healthy individuals or patients with Alzheimer’s disease.

The researchers then performed in vitro tests with HERV-K genes and healthy human neurons, and found that HERV-K killed neuronal cells.

Next, to help determine the role of the retrovirus in the pathogenesis of ALS, the scientists developed transgenic mice with an activated HERV-K gene. The mice grew to have ALS-like symptoms. They died earlier than normal and had problems with balance and walking that progressively worsened with age.

When the scientists inspected the brains, spinal cords, and muscles of these mice, they found that only motor neurons—the cells involved in ALS—were damaged. Cells in other parts of the nervous system remained healthy.

“We showed that motor neurons may be susceptible to activation of these genes during ALS,” Dr. Nath said. “The next order of question to ask is, can we develop drugs that may be able to prevent the virus from replicating, similar to an approach that we’ve taken for controlling HIV infection?”

To that end, the researchers have begun a clinical trial to find out if drugs used to treat HIV infection can block the activation and replication of HERV-K, and consequently affect the course of ALS.

“Ultimately, we hope the results will lead to effective treatments for a heartbreaking disorder,” Dr. Nath said.

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