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Genetic Disorder Drug Helps Reverse Heart Muscle Enlargement

Mice given BH4 had lower production of toxic free radicals from hypertension, study finds

FRIDAY, May 30 (HealthDay News) -- Tests on mice suggest that the drug BH4 may hold promise as a treatment for people with enlarged hearts, says a Johns Hopkins University study.

Currently, BH4 is used to treat a genetic disorder called phenylketonuria (PKU), a metabolic disorder in which a toxic buildup of a molecule called phenylalanine can cause brain damage.

In this study, the Hopkins team found that BH4 stabilized the pumping function of failing, enlarged hearts in mice and significantly decreased the size of the heart muscle in just over a month.

"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 [enlargement]," senior investigator Dr. David Kass, a professor at the Johns Hopkins University School of Medicine and its Heart Institute, said in a prepared statement.

"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," Kass said.

In this study, the researchers gave a daily dose of 5 milligrams of BH4 per 25 grams of body weight to 31 mice whose hearts were damaged by hypertension. This group of mice was compared to a group of mice with hypertension-damaged hearts who received a placebo.

After five weeks, the BH4 group showed "remarkable improvements" compared to the placebo group. Ejection-fraction measures of heart pumping function improved from 48 percent at the start of BH4 treatment to 59 percent by the end of the study. In the placebo group, average pumping function decreased from 48 percent to 35 percent.

Heart weight, as measured by muscle mass, decreased from an average of 290 milligrams at the start of BH4 treatment to an average of 209 milligrams by the end of the study. In the placebo group, average heart weight was 330 milligrams by the end of the study.

The BH4 group also showed improvements in other areas, including heart wall thickness, muscle cell size and fibrosis, and lowered production of dangerous free radicals.

The study was published in the May 20 issue of Circulation.

More information

The American Heart Association has more about heart failure.

-- Robert Preidt

SOURCE: Johns Hopkins University, news release, May 2008

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