Introduction
The implications of a recent discovery by scientists working at the National Institute of Health and published today in 'Science Translational Medicine' are so profound that I am including it as a separate article from the usual Public Information Content page.
For those of you reading who have a scientific background, I hope you agree that this exciting breakthrough could well be the discovery of the year and one of the most profound of the decade.
(As to a joint Nobel Prize for the scientists, if it was my decision, they would now be, at the very least, on the shortlist for next year!)
Patrick Emek
now read on.....................
Dormant viral genes may awaken to cause ALS
NIH human and mouse study may open an unexplored path for finding treatments
Scientists at the National Institutes of Health discovered that
reactivation of ancient viral genes embedded in the human genome may
cause the destruction of neurons in some forms of amyotrophic lateral
sclerosis (ALS). The results, published in Science Translational
Medicine, suggest a link between human endogenous retroviral genes
(HERVs) and ALS. The findings also raise the question of whether
antiretroviral drugs, similar to those used for suppressing HIV, may
help some ALS patients.
For generations, humans have been passing on genetic
remnants of HERV infections that may have happened millions of years
ago. Although nearly eight percent of the normal human genome is made
up of these genes, very little is known about their role in health and
disease.
“People call the genes for these viruses junk DNA. Our
results suggest they may become activated during ALS,” said Avindra
Nath, M.D., clinical director at the NIH’s National Institute of
Neurological Disorders and Stroke (NINDS) and a senior author of the
study. “Ultimately we hope the results will lead to effective
treatments for a heartbreaking disorder.”
Currently, there is no effective treatment for the more
than 12,000 Americans who live with ALS. This fatal disorder destroys
neurons that control movements, including speaking, walking, breathing
and swallowing. On rare occasions, HIV-infected, AIDS patients develop
ALS-like symptoms. In many of these patients, the symptoms can be
reversed by treatment with antiretroviral drugs. Previous studies found
reverse transcriptase, a protein encoded by retroviral genes, in the
blood of some ALS patients but its role in the disorder is unknown.
These observations prompted Dr. Nath and his team to
explore the possible link between retroviruses and ALS. Unexpectedly
they found that endogenous, or inherited, retroviruses may be involved
with ALS.
Viral genes in ALS - Scientists
studied human and mouse brains to show that genes for a seemingly
inactive and inherited virus may be linked to ALS. Courtesy of Nath lab, NINDS.
Initially, they showed that brain samples from ALS
patients had higher than normal levels of messenger RNA (mRNA) encoded
by genes of the human endogenous retrovirus K (HERV-K). A protein
encoded by a critical HERV-K gene, called env, was found in brain
samples from ALS patients but not from healthy individuals or patients
with Alzheimer’s disease. They also showed that activation of HERV-K
genes killed healthy human neurons grown in petri dishes.
To test the role of HERVs in ALS, the scientists
genetically modified mice so that their neurons activated the HERV-K
env gene. The mice 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 that control movements
and die 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,” said Dr. Nath.
Finally the scientists showed that activation of HERV-K
genes may be controlled by TDP-43, a gene-regulating protein that has
been strongly linked to ALS and known to control HIV production.
Genetically enhancing TDP-43 in human neurons increased the cells’
production of HERV-K mRNA and proteins whereas genetically blocking
TDP-43 in other cells reduced HERV-K reverse transcriptase activity.
Dr. Nath and his team are now collaborating with the ALS
center at Johns Hopkins University to study whether antiretroviral
treatments are effective at controlling HERV-K replication in a subset
of patients with ALS.
“We may have discovered a precision medicine solution for treating a neurodegenerative disorder,” said Dr. Nath.
This work was supported by intramural research programs
at the NINDS, the National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS) and the Eunice Kennedy Shriver National
Institute of Child Health and Development (NICHD).
For more information, visit:
www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/ALS.htm
www.ninds.nih.gov/disorders/motor_neuron_diseases/motor_neuron_diseases.htm
neuroscience.nih.gov/ninds/Home.aspx
www.niams.nih.gov/Research/Ongoing_Research/default.asp
www.nichd.nih.gov/about/org/dir/Pages/index.aspx
www.ninds.nih.gov/disorders/amyotrophiclateralsclerosis/ALS.htm
www.ninds.nih.gov/disorders/motor_neuron_diseases/motor_neuron_diseases.htm
neuroscience.nih.gov/ninds/Home.aspx
www.niams.nih.gov/Research/Ongoing_Research/default.asp
www.nichd.nih.gov/about/org/dir/Pages/index.aspx
NINDS
is the nation’s leading funder of research on the brain and nervous
system. The mission of NINDS is to seek fundamental knowledge about the
brain and nervous system and to use that knowledge to reduce the
burden of neurological disease.
The mission of the NIAMS, a part of the U.S. Department
of Health and Human Services' National Institutes of Health, is to
support research into the causes, treatment and prevention of arthritis
and musculoskeletal and skin diseases; the training of basic and
clinical scientists to carry out this research; and the dissemination
of information on research progress in these diseases. For more
information about the NIAMS, call the information clearinghouse at
(301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website
at http://www.niams.nih.gov.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD),
sponsors research on development, before and after birth; maternal,
child, and family health; reproductive biology and population issues;
and medical rehabilitation.
About the National Institutes of Health (NIH):
NIH, the nation's medical research agency, includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and Human
Services. NIH is the primary federal agency conducting and supporting
basic, clinical, and translational medical research, and is
investigating the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit www.nih.gov.
NIH...Turning Discovery Into Health®
References
Li et al. "Human endogenous retrovirus-K induces motor neuron
disease," Science Translational Medicine, September 30, 2015. DOI:
10.1126/scitranslmed.aac8201
