Friday, May 20, 2016

3 New Drugs for Fibromyalgia on the Way?


(91outcomes.com) - A new article discussed in detail three new drugs that could be on the way for fibromyalgia.  Fibromyalgia, a condition with chronic widespread pain at its core, is a presumptive for Veterans Affairs disability claims for veterans with Persian Gulf service from 1990 to the present.


The new drugs that could prove beneficial for fibromyalgia sufferers include:


  • IMC-1, "a combination of famciclovir (Famvir), a common antiviral, with celecoxib (Celebrex), an anti-inflammatory arthritis drug," for an FDA-cleared Phase III clinical trial in 2017.
  • Microgabalin (DS-5565), "which relieves pain by binding to the body’s calcium channels," but, with, "a unique binding profile and long duration of action at voltage gated calcium channels."
  • Tonmya (TNX-102 SL), a new under-the-tongue formulation of cyclobenzaprine HCL 2.8 mg to improve sleep quality, and, it is hoped thereby, other fibromyalgia symptoms.


Read the full, very well written article by Donna Gregory Burch for the National Pain Report, at:  http://nationalpainreport.com/three-new-fibromyalgia-drugs-could-be-on-the-way-8830514.html

VA Public Teleconference on Report Recommending Ending Certain Gulf War Research


DEPARTMENT OF VETERANS AFFAIRS

ACTION: Notice of opportunity to provide oral comments at a town-hall style session, and the opportunity to provide written comments.

SUMMARY: The Department of Veterans Affairs (VA) announces the opportunity on June 9, 2016, to comment on recent recommendations made to VA by the Institute of Medicine (IOM) in its report “Gulf War and Health, Volume 10: Update of Health Effects of Serving in the Gulf War, 2016” (http://nationalacademies.org/hmd/reports/2016/gulf-war-and-health-volume-10.aspx).

All comments are welcome, but VA specifically seeks those that address the recommendations made on pages 8-11 and pages 264-272 of the IOM report. The listening session will be a teleconference which is open to the public. The toll-free telephone number is (800) 767-1750, with access code 56978#.

Participants who wish to speak during the session should register by sending an email to victor.kalasinsky@va.gov by June 8, 2016.

Written comments must be received by June 15, 2016. Each speaker will have 5 minutes to speak. It is recommended that the speaker not read written comments, but rather highlight critical points in the written material that should be submitted.

DATE: Thursday, June 9, 2016, 1:00–3:00 p.m. Eastern Time

LOCATION: This is a teleconference only, (800) 767-1750, access code 56978#.

FOR FURTHER INFORMATION CONTACT: Victor Kalasinsky, Ph.D., Telephone:(202) 443–5600, victor.kalasinsky@va.gov.

New Study Finds Brain Function Differences in Gulf War Illness National Sample



SOURCE:   PubMed (published in Psychiatric Res.), April 30, 2016, by researchers Dr. CM Cooper, Richard W. Briggs, Robert Haley, et al.

http://www.ncbi.nlm.nih.gov/pubmed/27017423

ARCHIVED ABSTRACT:

 2016 Apr 30;250:33-41. doi: 10.1016/j.pscychresns.2016.03.004. Epub 2016 Mar 18.

Memory and functional brain differences in a national sample of U.S. veterans with Gulf War Illness.

Abstract

Roughly 26-32% of U. S. veterans who served in the 1991 Persian Gulf War report suffering from chronic health problems. Memory complaints are regularly reported by ill Gulf War veterans (GWV), but limited data verify their complaints. This study investigated episodic memory and brain function in a nationally representative sample of GWV, using a face-name memory task and functional magnetic resonance imaging during encoding. A syndrome classification system was used to subdivide ill GWV into the three major Gulf War Illness syndrome types, "impaired cognition" (GWV-1), "confusion ataxia" (GWV-2), and "central pain" (GWV-3). Memory and brain function of ill GWV were contrasted to deployed and nondeployed well GWV controls (GWV-C). Ill GWV exhibited impaired memory function relative to GWV-C but the patterns of functional brain differences varied. Brain activation differentiated the GWV-C from the ill GWV. The different syndrome types also differed from one another in several brain regions. Additionally, the current study was the first to observe differences in brain function between deployed and nondeployed GWV-C. These results provide (1) evidence of memory impairment in ill GWV and differentiate the syndrome types at a functional neurobiological level, and (2) the role of deployment in the war on brain function. 
Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS: 

Associative memory; Encoding; Gulf War Illness; fMRI
PMID:
 
27017423
 
[PubMed - in process]

New Study Shows Epigenetic Changes in Gulf War Toxin Rat Model

The study on which these findings are based was funded by the treatment-focused Gulf War Illness Research Program (GWIRP), within the Congressionally Directed Medical Research Program (CDMRP) administered by the U.S. Department of Defense health program.

Most notably, according to the study's findings, "Results from this study implicate a role for epigenetic alterations in GWI."

The study was funded in 2013 using FY12 funds.  According to the study's public abstract of what was proposed:

Gulf War Illness (GWI) is a chronic, multisymptom illness that affects approximately 25% of the 700,000 U.S. veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. Symptoms include severe fatigue, memory and concentration problems, poor coordination, headaches, chronic pain, gastrointestinal problems, skin rashes, irritability, and impaired immune function. Even after 20 years, the diagnosis of GWI remains elusive, useful treatments are lacking, and the cause of this complex illness is poorly understood. Nevertheless, it is generally believed that exposure to a combination of pesticides, pyridostigmine bromide tablets given as a preventative treatment against nerve agent exposure, and stress experienced by military personnel during the Gulf War is responsible for the chronic, debilitating symptoms affecting veterans with GWI. Animal studies have determined that exposure of rats to physiologically relevant doses of chemicals and stress used during the Gulf War results in neurobehavioral changes similar to those observed in GWI, as well as neuronal cell death in areas of the brain responsible for learning and memory, coordination of movements, and the maintenance of sensory and motor functions. In this application, we will investigate the molecular mechanisms responsible for the persistence of GWI symptoms, which may lead to the development of novel treatments as well as improved diagnostic markers for this disease. This proposal will be the first to evaluate microRNA (miRNA) changes that direct the late pathology of this multifaceted illness. 
MiRNAs comprise a recently discovered, important class of small ribonucleic acid (RNA) molecules that are abundant in many cell types and regulate the expression of target genes. Aberrant expression of miRNAs has been implicated in various neurodegenerative, cardiovascular, and metabolic diseases, as well as immune disorders and cancer. In addition, the discovery that miRNAs are detectable in the blood raises the exciting possibility that these molecules may serve as novel noninvasive biomarkers in the diagnosis of GWI. 
The objective of this study is to use an established rat model of GWI to (1) determine whether a combination of Gulf War-relevant chemical exposures and stress results in chronically altered miRNA expression patterns, increased inflammatory mediators, and increased neuronal cell death in the brain and spinal cord; and (2) determine the detectability of miRNA changes in the blood as potential noninvasive biomarkers of GWI. Results from this study will provide the foundation for future investigation in Gulf War veterans aimed to determine whether miRNA levels in blood distinguish ill from healthy veterans. In addition, identification of long-term miRNA changes will provide greater insight into the disease process of GWI and will also enable the identification of molecular pathways that can be targeted for the development of new treatments. Identified pathways may also reveal existing medications known to target these pathways that are currently approved for other indications and that may be used to treat Gulf War veterans as well.
For more information, see the project's abstracts at:  http://cdmrp.army.mil/search.aspx?LOG_NO=GW110033


***

SOURCE:   PubMed (published in Neurotoxicology), May 11, 2016, researchers Dr. Lisa M. Pierce et al.

http://www.ncbi.nlm.nih.gov/pubmed/27179617

ARCHIVED ABSTRACT:

 2016 May 11. pii: S0161-813X(16)30085-7. doi: 10.1016/j.neuro.2016.05.007. [Epub ahead of print]

Long-Term Epigenetic Alterations in a Rat Model of Gulf War Illness.

Abstract

Gulf War Illness (GWI) is a chronic, multisymptom illness that affects 25% of the 700,000 US veterans deployed to the Persian Gulf during the 1990-1991 Gulf War. Central nervous system impairments are among the most common symptoms reported, including memory dysfunction and depression. 
After 25 years, the diagnosis remains elusive, useful treatments are lacking, and the cause is poorly understood, although exposures to pyridostigmine bromide (PB) and pesticides are consistently identified to be among the strongest risk factors. 
Epigenetic changes including altered microRNA (miRNA) expression and DNA methylation play an important role in in learning, memory, and emotion regulation and have been implicated in various neurological disorders. In this study, we used an established rat model of GWI to determine whether 1) chronic alterations in miRNA expression and global DNA methylation and DNA hydroxymethylation are mechanisms involved in the pathobiology of GWI, and 2) plasma exosome small RNAs may serve as potential noninvasive biomarkers of this debilitating disease. 
One year after a 28-day exposure regimen of PB, DEET (N,N-diethyl-3-methylbenzamide), permethrin, and mild stress, expression of 84 mature miRNAs and global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) content were analyzed in the brains of GWI rats and vehicle controls by PCR array and enzyme-linked immunosorbent assay, respectively. 
Plasma exosome RNA next-generation sequencing analysis was performed in pooled samples to discover potential noninvasive biomarkers. We found that combined exposure to low doses of GW-related chemicals and mild stress caused epigenetic modifications in the brain that persisted one year after exposure, including increased expression of miR-124-3p and miR-29b-3p in the hippocampus and regional alterations in global 5mC and 5hmC content. 
GW-relevant exposures also induced the differential expression of two piwi-interacting RNAs (piRNAs) in circulation (piR-007899 and piR-019162). 
Results from this study implicate a role for epigenetic alterations in GWI. 
Evaluation of the diagnostic potential of plasma exosome RNAs in veterans with GWI is warranted.

Published by Elsevier B.V.

KEYWORDS: 

DNA methylation; Epigenetics; Gulf War Illness; Pesticides; Pyridostigmine bromide; microRNA
PMID:
 
27179617
 
[PubMed - as supplied by publisher]