MS Research Roundup: January 12, 2015
Pain Comes Before Myelin Loss; HPV Vaccine Not Linked to MS; Retroviruses Common in Genomes & Activate B Cells; Posthumous Plea for Right-to-Die Reform; Oscar Wilde’s Wife May Have Had MS
MS Research Roundup collects items of interest to multiple sclerosis researchers from around the Web. Send us your tips: firstname.lastname@example.org.
Pain From Lost Myelin-Making Cells
Pain can accompany other symptoms in MS, most commonly a continuous burning pain or sensitivity to touch and cold. A new study in mice found that the pain may arise from the dying myelin-making cells, known as oligodendrocytes, well before the inflammatory response and the loss of myelin around the neurons. In the study, researchers used a genetic technique to selectively kill oligodendrocytes. “The consequences were swift and striking,” wrote Stephani Sutherland at the Pain Research Forum. Within days, the mice developed hypersensitivity to annoying mechanical and cold stimuli, but not to heat. The sensitivity coincided with the death of the cells. The unsupported myelin sheathing remained intact for about 3 weeks. As others have observed, “the entire myelin compartment can appear to pinch off from the dying oligodendrocyte and survive for some time as a cushion around the axon, even supporting axonal energy metabolism for a significant amount of time,” co-author Klaus-Armin Nave, Ph.D., of the Max Planck Institute for Experimental Medicine in Göttingen, Germany, told Sutherland. The findings suggest that oligodendrocyte dysfunction contributes directly to pain. The work was led by Rohini Kuner, Ph.D., at the University of Heidelberg, Germany, and reported December 1 in Nature Communications. (Nature, Pain Research Forum)
HPV Vaccine Not Linked to MS
Researchers reported no increased risk of multiple sclerosis or any other similar central nervous system conditions in girls and women who received a human papillomavirus (qHPV) vaccine (Gardasil, Merck). Researchers analyzed data from nearly 800,000 Danish and Swedish girls and women ages 10 to 44 between 2006 and 2013. They identified over 4,300 multiple sclerosis cases and 3,300 cases of other demyelinating diseases in the cohort. Of these, only 73 and 90 cases, respectively, occurred within 2 years of vaccination. “Previous controlled observational studies have been unable to reliably confirm or refute a potential association with qHPV vaccination,” the authors wrote in their January 6 paper in JAMA. Concerns about MS risk have “been fuelled by social and news media reports of cases occurring after HPV vaccination, and an increasing number of case reports published in the medical literature describing vaccine recipients who developed multiple sclerosis as well as other demyelinating diseases,” according to a JAMA news release. The response to vaccines may be weaker in some treatment regimes after an MS diagnosis, a review found last year. (Forbes, JAMA Network)
Endogenous Retroviruses: Common and Immune Activators
One of the more unusual factors underlying MS may be reactivation of ancient remnants of retroviruses that inserted their DNA into the evolving human genome, an idea supported by a recent epidemiological study finding almost no overlap between MS and HIV in the antiretroviral treatment era. Two recent papers report that such endogenous retroviruses (ERVs) are common to many species and help activate the immune system. In one study, researchers from Uppsala and Lund universities in Sweden analyzed about 36,000 ERVs from 65 vertebrate genomes, including fish, humans and other primates, farm animals, birds, reptiles, and cats and dogs. ERVs are “incredibly common” and can switch among distantly related vertebrate hosts, the team reported December 22 in the PNAS Online Early Edition. Another study showed that ERVs can mobilize B cells to rapidly produce antibodies against pathogenic antigens in mice. Indeed, the results suggest the dead viruses are critical for the specific response of B cells in the absence of T cell mediation. Researchers at the University of Texas Southwestern Medical Center and Karolinska Institutet in Stockholm, Sweden, traced the B cell signaling pathways triggered by sugary structures on bacteria and viruses. The stimulated B cells produced a wide range of ERV RNA transcripts from across the genome, which were then also reverse-transcribed back into the DNA. The findings were published December 19 in Science. (Ars Technica, EurekAlert!, Genetic Engineering & Biotechnology News, GenomeWeb, The Scientist)
MS Patient Pleads for Reform in Right-to-Die Laws
Debbie Purdy, a person with primary progressive MS (PPMS) and a right-to-die campaigner, died on December 23, 2014, at a hospice in her home city of Bradford, England. She was 51 and had been living with PPMS for 20 years. Purdy passed away after refusing food. In 2009, she successfully challenged a British suicide law. Though they did not reform the law, the court created a set of guidelines that allowed Purdy’s husband to accompany her to a Swiss clinic where she originally wished to die. But the hard-won guidelines that allowed Purdy to die the way she wished still need to be written into law, Purdy wrote in an article published after her death by The Independent. The proposed Lord Falconer’s Assisted Dying Bill would allow patients in the United Kingdom to seek assisted dying, but only if they are both terminally ill and within 6 months of their death. The bill does not cover people like Purdy who have an incurable chronic condition. In the United States, assisted death is also largely inaccessible to patients, although public opinion is changing. No U.S. federal laws exist on the matter, and laws for physician-assisted death exist only in Oregon, Washington state, and Vermont (though New Mexico and Montana have other laws that essentially allow for physician-assisted death). In a related article, U.S. healthcare law attorney Miles Zaremski, J.D., suggested that the deaths of ill people like Debbie Purdy be seen not as suicide or even “assisted suicide” but as a heroic and considered decision. (CBS News, MedPage Today, ProCon.org, The Guardian, The Independent)
Oscar Wilde’s Wife May Have Had MS
Constance Wilde, wife to writer and poet Oscar Wilde, suffered from a great many things in life. One of her ailments may have been MS, according to letters to her brother described in a recent article published in The Lancet. Wilde’s mysterious illness—beginning in 1889 with “lameness” in the right leg—will sound familiar to many physicians. Over 9 years, Wilde suffered from a few relapses that gradually chipped away at her mobility and left her fatigued, in pain, and with a tremor in her right arm. Though MS was already known to the medical community by that time, it was poorly understood, and Wilde’s condition went misdiagnosed by “eccentric medics.” The letters also revealed that a botched myomectomy (removal of fibroids from the uterus) may have led to Wilde’s untimely death. Only 4 days after the procedure, Wilde developed intense vomiting and died from presumed dehydration. Wilde’s grandson, Merlin Holland, originally discovered the letters and sent them to Ashley Robins, M.D., of the University of Cape Town Medical School in South Africa for assessment. Holland said that he hoped the new information would dispel previous speculation that Wilde met her fate via damage to her spine caused by an accident or even syphilis contracted after one of her husband’s affairs. (Daily Mail, Medical News Today, The Guardian, The Lancet, The New York Times ArtsBeat Blog)
Stephani Sutherland is a contributor to MS Discovery Forum.