A virus that had long been spliced into the human genome may play a role in amyotrophic lateral sclerosis (ALS) the deadly muscular degenerative disease that paralyzed baseball great Lou Gehrig, and eventually took his life. This is the controversial conclusion of a new study, which found levels of human endogenous retrovirus K (HERV-K) higher in the brains of 11 people who died of the disease.
"This is certainly an interesting and provocative work," said Raymond Roos, a neurologist at the University of Chicago in Illinois who treats and studies of ALS, but has not participated in the conclusion . yet even scientists behind the work caution that more research is needed to confirm the link. "I'm very careful to say HERV-K does not cause the disease but can play a role in the pathophysiology," says study leader AVINDRA Nath, a neuroimmunologist the National Institute of neurological disorders and Stroke in Bethesda, Maryland. "The thing is damn in the chromosomes to start. It will be very difficult to prove causation."
There was another retrovirus, HIV, which led to the first Nath suspect a link between the virus and ALS. In 06, it was to help a patient to control his HIV infection with antiretroviral drugs when he noticed that the SLA of man has also improved. "It intrigued me, and I looked in the literature of ALS and saw that people had reported they could see reverse transcriptase in blood." reverse transcriptase, an enzyme that converts RNA to DNA is a hallmark of retroviruses, which use to insert copies of their genes into the chromosomes of their host.
No study had ever found a convincing retrovirus in patients with ALS. But the researchers only looked at viruses that came from outside the body. About 8% of the human genome consists of endogenous retroviruses "" such as HERV-K, which are likely the remains of old viruses. These retrovirus initially infected an egg cell or human sperm and entrenched themselves in the chromosomes, which allows them to spread from one generation to another. The finally deactivated DNA mutations retroviral incorporated.
In 2011, Nath and colleagues reported they had found increased levels of expression for HERV-K gene in the brains of autopsied people who died of ALS . Their new study, published online today in Science Translational Medicine , is based on previous work with analyzes of more brains and evidence supporting tube experiments and mouse test.
In about 10% of people with ALS, someone else in the family has the disease, suggesting that it comes from an aberrant gene inherited. Nath and colleagues focused instead on what is known as sporadic ALS: where people have no family history of the disease. Strengthen their 2011 study, the team found high levels of three different HERV-K genes in the brain autopsied ALS. Researchers are not isolate the virus itself, which notes Nath is logistically difficult because it would have to analyze the brains "fresh" soon after death.
Researchers have also shown in test tube experiments that the addition HERV-K genes to neuronal cultures led to a significant decrease of the cells. Using as the electroporation technique known to insert a HERV-K gene in the brains of embryonic mice, the researchers showed neuronal lesions similar. The researchers then developed mice that express HERV-K gene in all neurons. Again, the gene leads to neural mayhem, and the animals had similar muscle problems to what is observed in patients with ALS.
retrovirologists Some warn that the evidence remains thin that endogenous virus causes ALS. John Coffin who studies HERV-K at Tufts University in Boston, notes that high expression levels of genes of this retrovirus found in many conditions, including breast cancer, multiple sclerosis, schizophrenia, and melanoma, but none has been conclusively shown to be caused by it. "There are many documents like this," said Coffin. "The upregulation of the endogenous virus group is a very common finding."
Coffin said "group" because there are about 0 different HERV-K, and that's another concern that has labor laboratory Nath: the study does not show that all ALS patients have exactly the same version of the virus in their brains "I. am quite prepared to accept that there is toxicity, but I'm never quite sure what to do these kinds of experiences, "said Coffin. He notes that in the 1970s and 1980s, so many researchers wrongly asserted that exogenous human viruses-those who move between people or tumors commonly, humans and animals caused that they became known as "virus rumor." "There is a good amount of buzz around virology endogenous retroviruses responsible for the disease."
Even Nath stressed that he wants other labs to confirm the findings of his team. "I work with HIV for many years, and I am aware of the pitfalls, and that's why we wanted to ensure that we were very, very careful before we stuck our necks out," said Nath. "It took us 10 years to produce this document."
Nath is launching a clinical study to evaluate the impact of treatment of ALS patients who have high levels of HERV-K genes expressed in blood with a combination four antiretroviral drugs used to treat HIV infection. The Phase I study will mainly determine if treatment for 24 weeks can lower gene expression to undetectable levels HERV-K, but Nath also monitor the progression of the disease. Whether the anti-HIV drugs will even have an impact on HERV-K does not know. Drugs targeting reverse transcriptase and protease enzymes, both viruses depend, but there are differences between the HERV-K versions and HIV.
Coffin, who warns that antiretroviral toxicities have said the trial is madness. "The reason for this is non-existent," he said. Nath counters that there are about 40 cases described in the literature of ALS patients taking antiretrovirals, but it is difficult to make sense of these reports, about half of the claimed improvements. "No one has ever made a systematic study," he said.
Again, Nath allows increased expression of HERV-K genes in ALS patients may simply be the result of something else that causes real damage. "The reasons for skepticism are very valid," Nath said. "We could be wrong too."
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