MedicalResearch.com Interview with:
Dimitry N. Krementsov PhD
Research Associate
University of Vermont
Burlington, VT 05405
Medical Research: What is the background for this study? What are the main findings?
Dr. Krementsov: Multiple sclerosis (MS) is the most common disabling neurologic disorder affecting young adults. The disease is initiated by the individual’s own immune system attacking the central nervous system (brain and spinal cord).Multiple sclerosis is complex and is controlled by the interplay between sex/gender, genetics, and environmental factors. How this happens is not well understood, but an intriguing clue is that MS incidence over the last 50-100 years has been increasing in women and not men, suggesting that a recent environmental change is affecting MS preferentially in females.
There are several well-documented risk factors for Multiple Scleroisis, including
Epstein-Barr virus infection, low sunlight exposure, low vitamin D, and smoking. Recent studies have suggested the existence of a new risk factor – high intake of dietary salt. In our study, we sought to understand how this environmental factor may interact with genetics and sex.
We used an animal model of MS, called experimental autoimmune encephalomyelitis (EAE), in laboratory mice. The advantage of this approach is the ability to precisely control both the genetics and the environment, something that cannot be done in epidemiological studies in humans. Just as in previous studies, we found that when mice were fed a high salt diet, their MS-like disease got worse.
Importantly, we found that this was dependent on genetics and sex; when we varied the genetic background of the mice, we saw three different outcomes:
1) an effect of salt in both males and females,
2) an effect only in females, and
3) no effect in either sex.
Dr. Vittorio Gallo[/caption]
MedicalResearch.com Interview with:
Dr. Vittorio Gallo PhD
Center for Neuroscience Research
Children’s Research Institute
Children’s National Medical Center
Washington, DC 20010
Medical Research: What is the background for this study? What are the main findings?
Dr. Gallo: Astrocytes are cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, and help maintain homeostasis. In many neurodegenerative disorders – including multiple sclerosis (MS) –astrocytes undergo a cellular and biochemical transformation called reactive gliosis. This process significantly impacts – both positively and negatively – neural regeneration. Reactive astrocytes (RAs) synthesize and release a peptide called Endothelin-1 (ET-1). Gallo and his team previously demonstrated that ET-1 is expressed at high levels by RAs in multiple sclerosis (MS) lesions and that – in animal models of MS – this peptide inhibits repair by delaying oligodendrocyte maturation and remyelination.
The main finding of the study published in Cell Reports is the identification of the cellular and molecular pathway that mediates the inhibitory effects of ET-1 on oligodendrocyte regeneration and remyelinaton in demyelinated lesions. In particular - by using pharmacological and genetic approaches - the study demonstrates that the ET-1 acts selectively through the ET-receptor B (ENDRB) on astrocytes - and not oligodendrocytes - to indirectly inhibit remyelination.
Prof. Voskuhl[/caption]
MedicalResearch.com Interview with:
Professor Rhonda Voskuhl, M.D.
Jack H. Skirball Chair in MS Research
Director of the UCLA MS Program
David Geffen School of Medicine
University of California, Los Angeles
Medical Research: What is the background for this study? What are the main findings?
Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment.
