Cholesterol Transport Protein Implicated in MS

Megan Brooks

November 21, 2013

SAN DIEGO, California — Blood levels of the reverse cholesterol transport protein apolipoprotein A1 (ApoA1) are low in patients with multiple sclerosis (MS) and correlate with disease severity, new research shows.

ApoA1 is the most abundant component of high-density lipoprotein cholesterol and is known to protect against inflammation.

"Considering that the levels of this protein can be modified by currently used cholesterol medications, better understanding of this protein could lead to new treatments for multiple sclerosis," lead author, Lidia A. Gardner, PhD, from the University of Tennessee Health Science Center in Memphis, said in a statement.

The results were presented here at Neuroscience 2013, the annual meeting of the Society for Neuroscience.

ApoA1 Levels Lower in Severe MS

Dr. Gardner and colleagues investigated ApoA1 levels in 53 patients with relapsing-remitting MS, 50 with secondary progressive MS, 53 with primary progressive MS, and 57 healthy controls.

"Remarkably, all MS patients had less ApoA1 than controls," they report in a meeting abstract.

ApoA1 was reduced by approximately 25% in patients with relapsing-remitting MS, 50% in those with secondary progressive MS, and 75% in patients with primary progressive MS, the most severe form of the disease.

Studies in the mouse model of MS (experimental autoimmune encephalomyelitis) confirmed that mice with low ApoA1 exhibited worse symptoms.

"Our research shows the importance of ApoA1 in MS. Increased ApoA1 levels might be protective and beneficial for MS patients," Dr. Gardner told Medscape Medical News.

"We are currently working to expand our understanding of the role this protein plays in MS. We are continuing this project to identify regulators of ApoA1 formation under inflammatory conditions," she said.

Beyond Statins

Several studies have investigated the use of statins in patients with MS, with largely negative results. For example, results from the SIMCOMBIN trial in over 300 patients found no benefit of simvastatin added to interferon in relapsing-remitting MS, as reported by Medscape Medical News.

"Statins in addition to lowering harmful LDL cholesterol are supposed to reduce inflammation, and this is what prompted some investigators to use statins in MS patients," Dr. Gardner said in an interview.

She noted that "statins work on acetyl-CoA pathway; they bind HMG-CoA [hydroxymethylglutaryl coenzyme A] reductase, while ApoA1 is an integral component of a reverse cholesterol transport pathway. Therefore, we need to concentrate on a different biological pathway [from statins] for potential drugs to improve amount of good cholesterol in MS and other patients. This is what we are planning to do in our future studies," Dr. Gardner said.

The study was supported by the National Multiple Sclerosis Society. The research was done in the Laboratory of Viral and Demyelinating Diseases, University of Tennessee Health Science Center and Veterans Affairs Medical Center-Memphis, under the direction of Michael C. Levin, MD, professor of neurology. Dr. Levin currently consults for Gerson Lehrman Group and in the past (>5 years ago) for Biogen Idec, Teva, and Serano. Dr. Gardner has disclosed no relevant financial relationships.

Neuroscience 2013. Abstract 404.01. Presented November 11, 2013.

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