MS Research Roundup: October 3, 2014

MS Research Roundup collects items of interest to multiple sclerosis researchers from around the Web. Send us your tips: tips@msdiscovery.org.

Stem Cell Safety Trials in MS

Experimental stem cell therapies are chugging along, say two stories this week about progress in two trials. One approach used mesenchymal stem cells derived from each person’s own bone marrow. At the ACTRIMS-ECTRIMS meeting in September, researchers from the Cleveland Clinic announced results from an open label phase 1 trial in 24 patients with relapsing-remitting MS (RRMS). “Safety was excellent. The cell infusion was well-tolerated and there were no treatment-related severe or serious adverse effects,” lead researcher Jeff Cohen, M.D., of the Cleveland Clinic Mellon Center for MS Research told Medscape (free log in required). However, the researchers observed no meaningful clinical benefits save for small improvements in the Expanded Disability Status Scale in a few patients.

Recent research out of Mount Sinai Hospital in New York, NY, suggests that mesenchymal-like placental cells cultured from human tissue are also safe for MS patients. Placental stem cells are isolated and cultured from human placental tissue. Researchers tested the treatment in 10 patients with RRMS and six patients with secondary progressive MS. The phase 1b study was published online this week in Multiple Sclerosis and Related Disorders, though it does not appear to be listed at ClinicalTrials.gov. (Cleveland Plain Dealer, ClinicalTrials.gov, Medscape, MedPage Today, Mount Sinai Hospital)

Copaxone Meets Its Match in Generic

In the United States, MS drugs cost patients—or their health insurance plans—an estimated $40,000 to $50,000 per year. That makes a potential generic drug huge news. A phase 3 head-to-head trial of a generic version of glatiramer acetate versus the original Copaxone (Teva) suggested that the generic version works as well as the brand name for new lesions (as measured by T1 gadolinium-enhancing MRI) and reducing relapses, with similar rates of adverse events. If approved by the U.S. Food and Drug Administration, this could be the first U.S.-approved generic drug for MS. The researchers tested the generic against both Copaxone and a placebo in 735 patients with RRMS for 9 months. Of course, researchers are still nailing down exactly how the original drug works. In an article published earlier this week in JAMA Neurology, Nancy Monson, Ph.D., and colleagues at the University of Texas Southwestern Medical Center in Dallas concluded that some of Copaxone’s therapeutic benefit comes from its effect on dysregulated B cells. However, they could not confirm that it does so by restoring B cells’ ability to produce cytokines, as some theorize. (Cleveland Plain Dealer, ClinicalTrials.gov, Fox News, HCP Live, PubMed)

Epigenetics Uncover Innate Secrets

A systematic look at the epigenetics of blood cells shows unexpected changes in the immune response of monocytes and macrophages, according to studies published in Science on September 26. As activated monocytes in the blood move into tissue and differentiate into macrophages, one study found, the macrophages—considered members of the innate immune system—achieve a kind of “memory,” a characteristic normally attributed to cells in the adaptive immune system. The other study showed that these “trained” macrophages completely shift their metabolic pathway when transitioning from monocytes, switching the primary energy source from oxygen to glucose. “If you block that transition, … you block the training aspect [of macrophage development],” Hendrik Stunnenberg, Ph.D., of Radboud University in The Netherlands told GenomeWeb Daily News (free log-in required). In MS, monocytes invade the inflamed brain and spinal cord and seem to attack the myelin. Understanding the role epigenetic factors play in monocytes and macrophages may shed light on the disease. (If you need to brush up on your epigenetics, we published a primer here.) The studies were part of the European Blueprint consortium to understand the epigenome of hematopoietic cells. Blueprint, in turn, is part of a larger initiative called the International Human Epigenome Consortium. (Science, GenomeWeb Daily News, The Scientist)

One Brain, Many Genomes

“It’s hard to keep a genome intact when you have to divide so many times,” said Christopher Walsh, M.D., Ph.D., earlier this week at a lecture at Harvard University. He was explaining recent findings from his lab (here and here) showing that a person’s genome can vary from neuron to neuron in both healthy and pathological brains. Beginning with the first division of a fertilized egg, the genomes of cells pick up spontaneous, or somatic, mutations. People usually think of somatic mutations as associated with cancer. But many somatic mutations are not carcinogenic. Walsh, a neurologist at Boston Children’s Hospital and Howard Hughes Medical Institute (HHMI) investigator, and others have found similar types of mutations in some brain diseases using a more sensitive next-generation sequencing method and confirming it with other techniques. Some of the mutations exist only in a small percentage of cells, so they may not show up in blood samples or in traditional genetic testing. Some can be found only in the brain, if the mutations happened after the cells separated to create the brain. In the case of one boy who had half of his overgrown brain removed, Walsh found the key mutation in about one-third of neurons and about one-quarter of glia cells. Some researchers think the brain’s genetic diversity may be mostly a good thing, helping the brain to adapt. After all, the genetic shuffling that can produce hundreds of millions of distinctive receptors helps our immune system recognize infectious invaders it’s never seen before. And, yes, the technique could be used to study MS, Walsh told MSDF after the lecture. All it takes is fresh frozen brain samples, learning the tricky techniques, and sufficient funding. (HHMI, Quanta Magazine, SFARI, Vector blog)

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