viggster
Senior Member
- Messages
- 464
Neurovirologist Avindra Nath is leading the new NIH intramural study on ME/CFS. Looking through his publications, I found this interesting conference report from last year. Turns out that Nath and others have found preliminary evidence that human endogenous retroviruses are active and causing harm in MS, ALS, and type 1 diabetes. This whole field is very new and very young. However, it's interesting and at some point when patients are speaking with NIH folks someone should ask Nath if he's going to look for activated HERVs in the ME patients. HERVs are sections of DNA we all carry that encode ancient viruses. Not so long ago, someone discovered these viruses could be reactivated and brought back to life. HERVs are difficult to study, but I was surprised to read in this conference report that a phase 2 clinical trial is underway testing an anti-HERV drug in MS.
http://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-015-0051-7
(open source paper...free to download)
Here's the summary section at the end of the paper:
This first iteration of the ‘HERV & Disease’ workshop
provided the opportunity to bring together scientists and
clinicians with diverse expertise to share data and ideas
about the biology of HERVs and the possible impact of
these elements in health and disease. The event came
more than two decades after the discovery of the first
HERV-W element isolated from an MS patient, a finding
that has been the subject of much controversy and
debate in the community. How could viral elements assimilated
within the genome of humans trigger diseases
in certain patients but not others? Many laboratories
have invested a considerable effort to clarify this issue,
yielding important clues acting at different levels. First,
recent advances in genomics have started to provide
solutions to the technical challenges posed by the genetic
complexity and repetitive nature of HERVs in the
human genome. This is best illustrated with HERV-K
insertions, a growing number of which have now been
shown to be polymorphic and to occur at low frequency
in the human population. Furthermore, at the geneenvironment
interface, there is growing recognition of
cross-talks between diverse infectious agents (including
non-retroviral viruses) and HERVs and of their interference
with inflammatory and cytopathic signaling pathways.
This particular role of environmental microbes
provides examples of etiopathogenic mechanisms by
which non-physiological HERV activation may occur
and may have biological effects. This would confer a “hit
and run” role for the many infectious factors often but
partially associated with these diseases and a central role
for HERVs that, once transcriptionally activated, can
Nath et al. Mobile DNA (2015) 6:20 Page 8 of 9
trigger and fuel downstream pathogenic cascades leading
to specific lesions or cellular dysfunctions. In parallel,
diseases associated with the activation of elements of the
HERV-W family have now been extended from MS to
other inflammatory neurological or neuropsychiatric diseases,
at least one other autoimmune disease (T1D) and,
partly or in association with other HERVs, in some cancer
states. In the case of HERV-K, evidence is mounting
for the involvement of the HERV-K envelope protein in
the etiopathogenesis of sporadic SLA, which represents
a potential breakthrough for our understanding of this
and other neurodegenerative diseases. So, this and many
other studies on HERVs open exciting prospects as well
as new challenges to elucidate multifactorial etiopathogenic
pathways and cellular mechanisms underlying the
etiology and progression of many poorly understood
pathologies. There is great hope that innovative therapies
will emerge from this research. In this respect, the
good results from early clinical trials (Phase I in healthy
volunteers and Phase IIa in MS patients) for the first
specific immunotherapy targeting an associated pathogenic
HERV protein (references of publications available
from the corresponding author), provide encouraging
and new perspectives for the patients.
http://mobilednajournal.biomedcentral.com/articles/10.1186/s13100-015-0051-7
(open source paper...free to download)
Here's the summary section at the end of the paper:
This first iteration of the ‘HERV & Disease’ workshop
provided the opportunity to bring together scientists and
clinicians with diverse expertise to share data and ideas
about the biology of HERVs and the possible impact of
these elements in health and disease. The event came
more than two decades after the discovery of the first
HERV-W element isolated from an MS patient, a finding
that has been the subject of much controversy and
debate in the community. How could viral elements assimilated
within the genome of humans trigger diseases
in certain patients but not others? Many laboratories
have invested a considerable effort to clarify this issue,
yielding important clues acting at different levels. First,
recent advances in genomics have started to provide
solutions to the technical challenges posed by the genetic
complexity and repetitive nature of HERVs in the
human genome. This is best illustrated with HERV-K
insertions, a growing number of which have now been
shown to be polymorphic and to occur at low frequency
in the human population. Furthermore, at the geneenvironment
interface, there is growing recognition of
cross-talks between diverse infectious agents (including
non-retroviral viruses) and HERVs and of their interference
with inflammatory and cytopathic signaling pathways.
This particular role of environmental microbes
provides examples of etiopathogenic mechanisms by
which non-physiological HERV activation may occur
and may have biological effects. This would confer a “hit
and run” role for the many infectious factors often but
partially associated with these diseases and a central role
for HERVs that, once transcriptionally activated, can
Nath et al. Mobile DNA (2015) 6:20 Page 8 of 9
trigger and fuel downstream pathogenic cascades leading
to specific lesions or cellular dysfunctions. In parallel,
diseases associated with the activation of elements of the
HERV-W family have now been extended from MS to
other inflammatory neurological or neuropsychiatric diseases,
at least one other autoimmune disease (T1D) and,
partly or in association with other HERVs, in some cancer
states. In the case of HERV-K, evidence is mounting
for the involvement of the HERV-K envelope protein in
the etiopathogenesis of sporadic SLA, which represents
a potential breakthrough for our understanding of this
and other neurodegenerative diseases. So, this and many
other studies on HERVs open exciting prospects as well
as new challenges to elucidate multifactorial etiopathogenic
pathways and cellular mechanisms underlying the
etiology and progression of many poorly understood
pathologies. There is great hope that innovative therapies
will emerge from this research. In this respect, the
good results from early clinical trials (Phase I in healthy
volunteers and Phase IIa in MS patients) for the first
specific immunotherapy targeting an associated pathogenic
HERV protein (references of publications available
from the corresponding author), provide encouraging
and new perspectives for the patients.