Multiple sclerosis genetics—is the glass half full, or half empty?

Jorge R. Oksenberg & Sergio E. Baranzini  About the authors

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Abstract

Multiple sclerosis (MS) is a common and severe CNS disorder that is characterized by myelin loss, chronic inflammation, axonal and oligodendrocyte pathology, and progressive neurological dysfunction. Extensive epidemiological data confirm that genetic variation is an important determinant of susceptibility to MS, and suggest that such variation also influences the timing of symptom onset, the course of the disease, and the treatment response. Multicenter international collaborations have allowed large and well-characterized sample collections to be assembled that, when coupled with high-powered laboratory technologies, afford the opportunity to analyze the genome with increasing resolution and detail. The seven MS genome-wide association screens that have been completed in the past 3 years have substantially lengthened the list of MS genetic risk associations. Nevertheless, our knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed, although progress is likely to be rapid in the near future. The ensuing challenge will be to design effective functional studies that convincingly link genetic variation to the underlying pathophysiology of MS. Establishment of such connections might translate into clinically useful genetic biomarkers and reveal novel targets for therapy. This Review briefly summarizes well-established concepts of MS epidemiology and susceptibility, and discusses new knowledge emerging from genome-wide association studies.

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Author affiliations

J. R. Oksenberg & S. E. Baranzini
Department of Neurology, School of Medicine, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0435, USA (J. R. Oksenberg, S. E. Baranzini).

Correspondence to: J. R. Oksenberg jorge.oksenberg@ucsf.edu

Published online 13 July 2010

Nature Reviews Neurology 6, 429-437 (August 2010) | doi:10.1038/nrneurol.2010.91

Healing the Heart with Bone-Marrow Cells

http://www.technologyreview.com/biomedicine/22676/?nlid=2042
A new treatment may help angina sufferers who are resistant to surgery and medication.

• Injecting the hearts of angina sufferers with cells extracted from their own bone marrow can reverse the condition and relieve its symptoms, a new study suggests.

• The Dutch cardiologists behind the placebo-controlled study say that the results may lead to radical new treatments for patients for whom surgery and medication bring little or no relief from this painful and debilitating condition, which results from narrowed arteries that cannot supply enough blood to the heart during exercise. All 50 subjects involved in the study were resistant to existing treatments.

• Three months after being given the injections, patients' hearts were less starved of blood, and they were able to exercise more, researchers report in the latest issue of the Journal of the American Medical Association.

• Lead researcher Douwe Atsma, a cardiologist at Leiden University Medical Center, in the Netherlands, hopes that follow-up studies, which are currently in progress, will also reveal lower death rates among those who received the treatment.
  

• Atsma's team first fed catheters through patients' femoral veins, up into the aorta, and then into the heart's left ventricle--the chamber that pumps oxygen-rich blood back in the circulation. By touching an electro-sensitive tip around the chamber's surface, the researchers were able to locate areas of low electrical activity, where diminished blood supply had caused cells to die. They built up a "map" of the left ventricular surface of all 50 patients.

• The researchers then took bone marrow from participants' hips and extracted the mass of mononuclear cells--an ill-defined mix of stem cells and progenitor cells.

• In 25 of the patients, the researchers injected around 100,000 cells into angina-affected areas on the ventricular surface, using a modified form of the same catheter. The remaining 25 patients received a placebo injection of saline.

• Three months after the treatment, more catheter tests showed that the average number of diseased grid areas in the hearts of treated patients had fallen from 4.2 to 1.8, or 57 percent. In patients given the placebo, the number fell from 3.8 to 3.1--a significantly smaller 18 percent reduction.

• Bone-marrow recipients were also able to expend more energy on an exercise bike after three months: 114 kilocalories, compared with 107--a small but significant change. Placebo patients experienced an improvement of just 101 kilocalories compared with 99.

• Earlier trials in which researchers sought to treat heart-attack victims with their own bone-marrow cells produced mixed results. Some studies found moderate improvements in a few measures of heart function, but none showed a clear health benefit.