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Drug therapy for PKU reverses heart damage
Date:5/13/2008

A pricy drug used to treat a rare but well-known genetic disorder may hold wider promise as a treatment for millions of Americans with potentially lethal enlarged hearts, due mainly to high blood pressure, a study from Johns Hopkins shows.

The common denominator in both phenylketonuria (PKU) and cardiac hypertrophy is the chemical tetrahydrobiopterin (BH4). In PKU, this enzyme coworker helps break down the molecule phenylalanine whose buildup is toxic to the brain. In the heart, BH4 helps build the chemical nitric oxide, which is needed for normal heart function and neutralizing toxic chemicals, called oxygen free radicals.

Doctors have used BH4 and diets that exclude phenylalanine for almost a decade to treat PKU, a so-called inborn error of metabolism that if left untreated causes irreversible brain damage. It affects an estimated 15,000 newborns in the United States each year.

Building on what has been known about BH4s activities, the Hopkins team, working with mice, found that treatment with BH4 stabilizes the pumping function of failing, enlarged hearts and dramatically shrinks the muscle size in a relatively short timeframe of just over a month. The teams findings appear in the May 20 edition of the journal Circulation.

Our results show for the first time the pivotal role played by BH4 in stopping and reversing the weakening and damage done even in severe cases to the heart muscle as a result of hypertension and subsequent hypertrophy, says study senior investigator David Kass, M.D., a professor at the Johns Hopkins University School of Medicine and its Heart Institute. This key evidence may help us develop new therapies that stop and reverse hypertrophy, preventing the disease from leading to end-stage heart failure and keeping affected individuals from needing heart-assist pumps or a treatment of last resort, the heart transplant.

Specifically, Kass and Belgian scientist, An Moens, M.D., a postdo
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Source:Eurekalert

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