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PHILADELPHIA – In preclinical studies using cell models that mimicked liver cells of patients with the rare disease Friedreich’s ataxia (FA), a widely used cholesterol-lowering drug increased a precursor of HDL (high-density lipoprotein), the “good cholesterol,” according to new research published in PLOS One from the Perelman School of Medicine at the University of Pennsylvania.

Decreased HDL and apolipoprotein A-I (ApoA-l) levels in the general population are associated with an increased risk of death from cardiomyopathy and heart failure.

“We found the FA patients had serum ApoA-I levels that were lower than healthy control subjects,” said senior author Ian Blair, PhD, a professor of Systems Pharmacology and Translational Therapeutics.

The next step of the research, conducted in collaboration with David Lynch, MD, PhD, a professor of Neurology at Children’s Hospital of Philadelphia (CHOP), showed that statins may be able to help Friedreich’s ataxia patients increase their naturally low ApoA-I levels and so increase their HDL levels, which might help prevent heart disease.

FA is a rare condition diagnosed in about in 50,000 people worldwide. It is the most common form of inherited ataxia, a condition characterized by a progressive loss of coordinated movement and balance. Onset of symptoms usually occurs in childhood, and most patients are confined to a wheelchair by their mid-to-late twenties. Most FA patients die from the thickening of their heart walls (hypertrophic cardiomyopathy) rather than from neurological issues.

In FA, the protein frataxin is made in insufficient amounts for mitochondria to function properly. This happens because of a mutation in the FXN gene, which results in reduced expression of frataxin protein. Frataxin is normally found in the mitochondria of cells and is involved in biochemical reactions that produce energy.

Using a highly specific and sensitive assay, the researchers found a 22 percent decrease in ApoA-I in the blood of FA patients compared with blood samples from non-affected healthy individuals. Using an experimental FA cell line, they also found that cells without frataxin produced lower levels of ApoA-I compared to controls. However, the cholesterol-lowering drug simvastatin increased the ApoA-I levels by 20 percent in these cells.

“I think that our findings provide compelling evidence for a trial of statins in FA patients to potentially reduce their cardiovascular risk,” Blair said. One issue is that higher doses of statins are associated with myositis (muscle inflammation) and rhabdomyolysis (destruction of skeletal muscle) so it would be essential to carefully monitor these side effects, he noted. In addition, co-administration of coenzyme Q10 supplement could help reduce the risk of muscle-related side effects. 

Overall, Blair maintains that the potential benefits to FA patients with low ApoA-I levels taking low doses of statins outweigh the potential risks. 

This research was funded by the Penn Medicine/CHOP Friedreich's Ataxia Center of Excellence, in partnership with the Hamilton and Finneran families.

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report’s survey of research-oriented medical schools. The School is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year.

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center — which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report — Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided $500 million to benefit our community.

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