ALS is a devastating disease that rapidly leaves a person unable to move, speak, or eat without assistance. It does this by attacking the nerves responsible for controlling voluntary movement, speech, and swallowing. Also known as Lou Gehrig’s disease, ALS affects only about 2 in every 100,000 people and is often fatal within 3 to 5 years of diagnosis. While much research has been done trying to uncover the cause of this debilitating disease, there is no definitive answer and an appropriate treatment still eludes us. What we do know about ALS is that only about 10% of cases are inherited through families while the other 90% have no identifiable cause. Research has found associations between proteins (SOD1), genes (C9orf72), and exposure to toxins. It is unlikely that there is any one cause of ALS; instead, there is likely to be a multitude of environmental factors that pair with genetic mutations to cause this horrible disease. Researchers from Maryland have added another factor to the growing list of possible ALS triggers by publishing a paper identifying how a class of ancient viruses that are embedded within our genes may play a role in ALS.
Inside each of the cells is the DNA that codes for all the things that make your body work. This collection of DNA and genes is referred to as the human genome. Embedded within this genome are little pieces of DNA that don’t belong to you. These pieces of DNA come from viruses that embedded themselves in your genome a long time ago. These viruses, called retroviruses, have the ability to put their own genetic information into your DNA for the purpose of high jacking your cells machinery to make millions of copies of themselves. The most well known retroviruses include HIV and hepatitis. Usually these viruses cause their hosts to become ill (as is the case with HIV/AIDS) but in the case of these ancient viruses, they have been in your DNA so long that they have become inactive. These viruses are called Human Endogenous Retroviruses (HERV’s) and make up 5-8% of all the DNA in your body. It has been speculated that these ancient viruses may have played an important role in shaping our evolution by modifying how certain genes work. Normally these viruses no longer do anything in our body, however under certain disease conditions, it is possible that they can become activated and play a role in disease development.
The research group out of Maryland found that in the brains of people who died of ALS there was increased amounts of one of these viruses, HERV-K. The group had shown this result in the past and it was met with skepticism. After all, we have years of research that shows these viruses don’t do anything in the body anymore. So to build upon the evidence the research team added the HERV-K viruses to nerve cells and saw that the cells began to die off. Next, they engineered mice to have HERV-K virus in their neurons and saw that the mice began to have muscular problems and nerve damage similar to the onset of ALS. This evidence gave more support to the idea that these viruses could be playing a role in neuron damage in ALS. Add to this the fact that there are cases described in the science literature of patients with ALS who are treated with anti-retroviral drugs that have some improvement in their symptoms and the story becomes interesting. This is because these drugs are designed to block viruses like HIV from replicating. The fact that they are working to improve the symptoms of ALS suggests that a retrovirus like HERV-K might be contributing to the disease. The research group is now undertaking a clinical trial to treat ALS patients who have high levels of HERV-K genes in their blood with anti-retroviral’s to systematically test if they get better.
The authors of the paper caution that this result is quite controversial in many research groups since it goes against many conventional ideas. However, at one point or another many great ideas went against convention, just ask Galileo. More concrete evidence will be needed to understand whether reactivation of these dormant HERV-K viruses causes nerve death and ALS or if this result if just a case of coincidental correlations. It is still too early to point the finger at HERV’s, and so we greatly anticipate the results of the clinical trial.
Photo Credit: ALS Coronal Frank Gaillard
Science Translation 
