Perindopril Prevents Onset of Heart Failure in Children with Duchenne Muscular Dystrophy

(I-Newswire) March 16, 2005 - "For the first time, we have shown that it is possible to slow progression in this rare degenerative disease", says lead investigator Professor Denis Duboc from the Cochin Hospital in Paris. "In DMD, the heart muscles are affected and cardiac problems are fatal in around 40% of children with DMD."

The five-year study, coordinated by the French Working Group of Heart Improvement in Myopathies and supported by the French Muscular Dystrophy Association (AFM) (through donations to an annual national Telethon) and Servier Laboratories, set out to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril in children with DMD. Perindopril is currently used to treat high blood pressure and heart failure.

In a double-blind study, 57 children aged 10 to 13 were recruited and randomly assigned to receive either perindopril or placebo for three years. Left ventricular ejection fraction (LVEF), a measure of the heart's pumping strength, was measured at 0, 36 and 60 months.

In the placebo group, eight children developed left ventricular dysfunction compared to only one child in the perindopril group. No fatal progression of heart failure was recorded during follow-up in the group of children receiving perindopril whereas three children did not survive the onset of heart failure in the control group. Perindopril was well-tolerated in the children studied.

"The study was relatively small-scale," says Professor Duboc. "Patient recruitment is always a problem with rare diseases (orphan diseases), but," he adds "the big advantage is that patients are perfectly homogenous in terms of genotype and of phenotype, and this enhances the reliability of the findings of these types of study, even though they are conducted on small patient populations."

Genetic markers of heart failure

"Looking beyond DMD, we hope that we can eventually pinpoint other genetic markers in individuals susceptible to developing heart failure and treat them before the first signs of heart disease in order to delay or even prevent the onset of heart failure," concludes Professor Duboc.

Duchenne Muscular Dystrophy

DMD - first described by a French physician called Guillaume Benjamin Armand Duchenne in the 1860s - is one of the commonest forms of muscular dystrophy, a group of inherited, degenerative diseases that cause progressive muscle weakness and wasting. Duchenne muscular dystrophy is caused by an absence of dystrophin, a protein that helps keep muscles intact. DMD tragically strikes children at a young age (2 - 6 years) and affects almost exclusively boys who rarely survive beyond their early 30s.2

References:

1 Duboc D et al., 'Effect of Perindopril on the Onset and Progression of Left Ventricular Dysfunction in Duchenne Muscular Dystrophy', Journal of American College of Cardiology, 2005; 45: 855-857

2 http://www.mdausa.org (Muscular Dystrophy Association website)

Duchenne Muscular Dystrophy Backgrounder

What is Duchenne Muscular Dystrophy?

Duchenne Muscular Dystrophy (DMD) is a debilitating genetic muscle disorder. One of nine muscular dystrophies, DMD is a serious condition which causes muscle weakness mainly in the arms, legs and spine, and can lead to severe breathing, heart problems and in some cases, learning difficulties. DMD occurs early on in life and can shorten life expectancy tremendously. DMD is named after the French neurologist Guillaume Benjamin Amand Duchenne who identified the condition in the late 1800's.

What causes DMD?

Duchenne Muscular Dystrophy is a generic disorder, caused by a lack of the protein, dystrophin. A gene on the X chromosome responsible for producing this protein fails. Dystrophin is essential in strengthening muscle cells, to help with structural support. Without this protein, muscle cells are severely weakened and progressively waste away.

Can this absent protein be replaced?

Unfortunately lost dystrophin protein cannot be replaced by eating foods high in protein. If the inherited protein-producing gene is deficient, nothing can be done to rectify this.

Who is affected by DMD?

DMD usually affects boys from the age of one to five years old, however on rare occasions it can also affect girls. This degenerative disease is so severe that DMD patients' life expectancy is reduced dramatically - they rarely survive beyond their early 30's.

What are the symptoms of DMD?

Most boys who have the disorder start showing signs of muscle weakness as early as one to three years of age. Toddlers are usually late in learning to walk compared with their peers, and calf muscles may be enlarged, known as pseudohypertrophy.

Children aged around three may fall regularly, have trouble getting up, running, and difficulties in climbing stairs. As the years progress so does DMD. Patients may begin to walk on their toes or balls of their feet in an unsteady motion, which can cause them to fall easily. Between the ages of eight and 11, the disorder becomes debilitating and nearly all patients lose the ability to walk.

How is DMD diagnosed?

Initially, a doctor will look into the family history of the child in conjunction with a physical examination. These can be very insightful, as they can determine if the muscle weakness is a result of problems with the muscles or nerves (motor neurons). Only weaknesses derived from the muscles characterise muscular dystrophy.

A blood test is also effective in diagnosing DMD. A blood test can detect if high levels of the enzyme creatine kinase, is present in the blood, indicating it's leakage from a damaged muscle. DMD sufferers have abnormally high levels of this enzyme present in their blood stream.

Once muscular dystrophy has been diagnosed, a muscle biopsy of the weakened muscle may also be conducted in order to define which form of the disorder the patient is suffering from.

Are people with DMD likely to suffer from other medical conditions as a result?

It is common for people with DMD to have additional health problems. Curvature of the spine (scoliosis) can develop, which causes serious discomfort, pain and also disfiguration. Scoliosis can only be treated surgically, however this is only considered as a last result.

As the muscles deteriorate, severe breathing and heart problems develop. In some cases, children also develop learning difficulties.

How many children are affected with DMD?

Approximately one in every 3,500 male births worldwide is affected by DMD.

In the UK around 100 boys with DMD are born each year, and there are around 1,500 boys with DMD living in the UK, at any one time.

In France there are currently approximately 2,000 boys with DMD.

Can DMD be cured?

Unfortunately, there is no cure for Duchenne Muscular Dystrophy as yet, however treatments are available to make DMD patients more comfortable and heighten their quality of life. A number of research projects are also underway, striving to find treatments for this devastating disorder.

AFM - Association Française contre les Myopathies
www.afm-france.org

Stéphanie Makin
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