05 October 2015
ByAppeared in BioNews 822
Researchers have found that ALS patients with no family history of the disease had higher levels of the ancient retroviral gene HERV-K env than patients with other neurodegenerative diseases, such as Alzheimer's.
Human Endogenous Retroviruses (HERVs) are viruses that integrated themselves into human chromosomes during repeated infections over several million years of human evolution. They make up around eight percent of human DNA, but most have accumulated mutations that render them inactive. Occasionally, however, they can reactivate and cause disease.
In 2006, neurovirologist Dr Avindra Nath of the National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, saw a young man who had both HIV, human immunodeficiency virus, and ALS – a degenerative disease that affects the neurons responsible for talking, walking and swallowing, among other motor functions. When the patient started taking antiretroviral drugs to treat his HIV, his ALS symptoms improved.
Following up this intriguing finding, Dr Nath noticed that reverse transcriptase activity (a sign of retrovirus infection) could be seen in ALS patients. 'I reasoned, if you have reverse transcriptase activity and you can't find an exogenous retrovirus, maybe there's an endogenous retrovirus,' said Nath.
Dr Nath and his team inserted either the whole HERV-K genome, or just the env gene, into human neurons in petri dishes. Once the virus (or viral protein) had integrated into the genome of the neuron and activated, it killed significant numbers of neurons.
The researchers also genetically engineered mice to express the virus in their neurons. The mice showed progressively worsening problems with balance and walking before dying prematurely. Analysis of their neurons after they died revealed structural changes associated with degeneration.
The findings, which were published in Science Translational Medicine, suggest that reactivation of the endogenous retrovirus HERV-K can trigger ALS in patients with sporadic (non-inherited) form of the disease.
Dr Nath is now launching a clinical study to see if ALS can be treated with antiretroviral drugs such as those used in the treatment of HIV. 'We haven't proven that the virus causes ALS; we've shown that the virus antiviral product may play a role in the pathophysiology of ALS,' Nath told The Scientist. 'Even if you don't know the cause, if you can find a key molecule in the pathway, you can block it and impact the course of the disease,' he said. 'We think we have a key molecule.'