Using The Herpes Virus To Target Pain

Today's post from idse.net (see link below) looks at a surprising development concerning the herpes virus and its relationship to pain treatment. It is hoped that by using the herpes virus in its latent stage (before it becomes active and leads to the complications many people are aware of) to act as a postman and deliver pain-blocking messages to nerve cells. The article is short but heavy on medical terminology, yet it's not difficult to get the idea of what they mean. Definitely an interesting development worthy of a read.

Harnessing the Herpes Virus To Precisely Target Pain
by Damian McNamara ISSUE: FEBRUARY 2014 | VOLUME: 1

The herpes simplex virus might start getting some good press for a change. Anesthesiology researchers at the University of Miami Miller School of Medicine, in Florida, are using the virus to deliver genetic instructions in the hope of rewriting chronic pain signals at the source.

Spurred by success in animal models and encouraged by results from initial trials in cancer patients, Shaunglin Hao, MD, PhD, Roy C. Levitt, MD, and their colleagues use the virus’s predilection for neurons to their advantage in delivering anti-nociceptive neuromodulating molecules directly to the dorsal root ganglia to treat chronic pain.

Herpes simplex virus (HSV) bears a genome big enough to carry a relatively large “payload” of genetic instructions compared with other vectors, according to the Miami researchers. In addition, HSV remains latent after it enters the neurons of sensory ganglia, a feature that allows gene transfer to continue while evading an immune system reaction, another positive aspect of this approach. Importantly, HSV rendered to prevent replication (“replication-defective”) can still deliver genes during the latency phase exclusively within the sensory nerves targeted.

“We are one of the few centers worldwide working with this innovative technology in preclinical studies,” said Dr. Levitt, director of translational research and clinical professor of anesthesiology, perioperative medicine and pain management at the institution. “We certainly hope to continue this close collaboration with the inventors and develop new applications and innovative uses of this technology to anesthesiology.”

The inventors are David Fink, MD, of the University of Michigan, Joseph C. Glorioso, PhD, of the University of Pittsburgh, and their colleagues at Periphagen Holdings, a team that pioneered this HSV-mediated gene-transfer strategy. The group has brought HSV vectors into the clinic in Phase I (Ann Neurol 2011;70:207-212) and Phase II clinical trials for the treatment of intractable cancer pain.

Blocking Pain Signals

The trials have assessed the effectiveness of a modified HSV that delivers a gene that encodes for preproenkephalin. Preproenkephalin is a precursor protein that cleaves to produce the endogenous opioid peptides met-enkephalin and leu-enkephalin. These enkephalin peptides inhibit pain signals in the spinal cord.

Dr. Fink, a neurologist, said his group plans another trial with the enkephalin vector. With funding from the National Institutes of Health and from the Department of Veterans Affairs, they are progressing toward clinical trials of an HSV vector expressing glutamic acid decarboxylase for neuropathic pain and an HSV vector expressing a neurotrophin for the prevention of neuropathy, he said.

Dr. Levitt said the applications of the approach for clinical medicine “seem almost limitless.” For instance, in anesthesiology, “I can envision an approach where we might treat a patient preoperatively with a nerve block and ‘activate’ the dormant pain treatment just before the surgery to treat acute pain, and possibly post-op to treat and/or avoid chronic pain development in susceptible individuals.

“Only time will tell us the true risk–benefit ratio of this approach as these clinical trials and large-scale patient-use progress and new applications are developed,” Dr. Levitt added. He predicted if the current trajectory of research continues and HSV-mediated gene transfer continues to prove safe and effective, a product launch could come within three to five years.

“This is the frontier of modern medicine and where our specialty will benefit enormously in the future,” Dr. Levitt said. “HSV-mediated gene therapy with localized delivery to sensory nerves important to the care of patients who experience pain will transform our specialty, and as a consequence, change the paradigm of current practice.”

Dr. Levitt reported no relevant financial disclosures. Dr. Fink is a co-inventor on patents related to this research.

http://www.idse.net/ViewArticle.aspx?d=Public%2BHealth&d_id=212&i=February+2014&i_id=1034&a_id=25906

The HIV Virus Itself Can Attack The Nervous System At An Early Stage

Today's post from the always reliable sciencedaily.com (see link below) reports something that will be of no surprise to people living with HIV across the world and that is that neuropathy very often appears from the early stages of infection. This gives proof to the theory that the virus itself attacks the nervous system. The accepted knowledge is that neuropathy in HIV is linked to older toxic HIV drugs and doctors are still continually surprised that people arrive in their surgeries with neuropathic symptoms, despite being on the most modern HIV medication combinations. The study mentioned here claims that the symptoms appear pre-medication treatment and generally disappear after treatment begins. However, there has to be some considerable doubt about this claim! Neuropathic symptoms don't disappear and nerve damage is, at the moment, generally irreversible. People living with HIV generally see a worsening of their symptoms over a period of time and end up on the treadmill of drugs designed to suppress the discomfort but not cure it. Perhaps the most relevant finding of the study is that after contracting HIV, many people will show signs of nerve damage, with all the symptoms that we're familiar with. The idea that this is linked to the older drug regimes is somewhat outdated but not totally incorrect and modern HIV drugs can cause nerve damage too. The problem is that it's clear that the HIV virus itself attacks nerve cells and especially mitochondria and although HIV medications (old or new) don't help, they're not exclusively responsible for neuropathy in HIV patients.

Neurologic symptoms common in early HIV infection
Much more extensive, though milder than previously thought 
Date:June 13, 2016 Source:University of California - San Francisco

A team led by researchers from UCSF and Yale has found that half of people newly infected with HIV experience neurologic issues. These neurologic findings are generally not severe and usually resolve after participants started anti-retroviral therapy.

"We were surprised that neurologic findings were so pervasive in participants diagnosed with very recent HIV infection," said study lead author, Joanna Hellmuth, MD, MHS, clinical fellow in UCSF's Department of Neurology. "While the findings were mild, it is clear that HIV affects the nervous system within days of infection. Since the majority of these neurologic issues were resolved with treatment, our study reinforces recommendations that people at risk for HIV test often and start antiretroviral treatment immediately if they are infected."

The research will be published in the June 10, 2016, issue of Neurology, the medical journal of the American Academy of Neurology.

The team examined 139 participants in the RV254 Thai cohort who were recently infected with HIV. The time from infection to entry into the study ranged from 3 to 56 days with a median of 19 days. At this stage, participants would not test positive on the common antibody tests for HIV since they have not been infected long enough for a robust specific immune response to take place. Fifty-three percent had neurologic findings, with a third experiencing cognitive deficits, a quarter having motor issues, and nearly 20 percent experiencing neuropathy. Many experienced more than one symptom. One participant was diagnosed with Guillain-Barré Syndrome, the only severe case found in the cohort.

"In the early days of the epidemic in San Francisco, approximately 10 percent of patients with recent HIV infection presented with dramatic neurological disease. But that was likely due to patients coming in early because of the severity of symptoms they were experiencing. The Thai cohort has given us an opportunity to look at a broad range of newly infected patients, analyze their neurological functioning systematically and follow them over time. We are gaining deeper insights into the degree to which early HIV affects the nervous system," said study senior author, Serena Spudich, MD, Yale associate professor of neurology.

All participants were offered and commenced antiretroviral treatment at diagnosis. Ninety percent of the issues present at diagnosis were resolved after one month of treatment, but 9 percent of the participants had neurologic symptoms that were still not resolved six months after starting therapy. In addition, neurological symptoms were associated with higher levels of HIV found in participants' blood.

The study participants underwent extensive neurologic assessments. Self reported symptoms were correlated with objective neuropsychological testing. In addition, a quarter of participants opted to undergo a lumbar puncture and almost half of the patients agreed to undergo a MRI.

"This is one of the first comprehensive studies scrutinizing the involvement of the nervous system in early infection. Since we have been able to maintain the cohort for five years now, we will be able to study whether there are any persistent abnormalities that need to be addressed. Additionally, the ubiquity of symptoms in early infection found in this study reinforces the need for the brain to be considered as a compartment containing latent HIV as we design cure studies," said study co-author, Victor Valcour, MD, PhD, UCSF professor of neurology.

Story Source:

The above post is reprinted from materials provided by University of California - San Francisco. The original item was written by Jeff Sheehy. Note: Materials may be edited for content and length.

Journal Reference:
Joanna Hellmuth, James L.K. Fletcher, Victor Valcour, Eugène Kroon, Jintanat Ananworanich, Jintana Intasan, Sukalaya Lerdlum, Jared Narvid, Mantana Pothisri, Isabel Allen, Shelly J. Krebs, Bonnie Slike, Peeriya Prueksakaew, Linda L. Jagodzinski, Suwanna Puttamaswin, Nittaya Phanuphak, Serena Spudich. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology, 2016; 10.1212/WNL.0000000000002837 DOI: 10.1212/WNL.0000000000002837

https://www.sciencedaily.com/releases/2016/06/160613105753.htm