Public Release: 

Experimental cancer drugs counter muscle deterioration seen in muscular dystrophy

Normal muscle function restored in dystrophic mice

Sanford-Burnham Prebys Medical Discovery Institute

(La Jolla, CA - September 17, 2006) -- Muscle weakness and fiber deterioration seen in muscular dystrophy can be countered by a class of drugs currently under study for their effects against cancer, a Burnham Institute study has found.

The report shed light on the potential use of these drugs, called histone deacetylase inhibitors, in promoting regeneration and repair of dystrophic muscles, thereby countering the progression of the disease, in two different mouse models of muscular dystrophy. Led by Burnham Institute assistant professor Lorenzo Puri, M.D., Ph.D., in collaboration with the Dulbecco Telethon Institute (DTI) of Rome and other colleagues in Italy and at the National Institutes of Health, the study was made available to researchers worldwide by expedited publication at Nature Medicine's website on September 17, 2006.

Puri's team discovered that ongoing treatment with the deacetylase inhibitor Trichostatin A, currently under clinical study for breast cancer, restored skeletal muscle mass and prevented the impaired function characteristic of muscular dystrophies. Importantly, these restored muscles showed an increased resistance to contraction-coupled degeneration--the primary mechanism by which muscle function declines in Duchenne muscular dystrophy and related dystrophies.

Indeed, muscles examined from dystrophic mice treated with Trichostatin A for three months displayed normal tissue architecture, as compared to the muscles examined from untreated, dystrophic mice. Furthermore, dystrophic mice receiving treatment were able to perform physical exercise (e.g. running on a treadmill) similar to normal, non-dystrophic mice.

Muscular dystrophy is a group of more than 30 genetic diseases, characterized by progressive weakness and deterioration of skeletal muscles. All are inherited, caused by a mutation in one of a group of genes responsible for maintaining muscle integrity. Puri's team studied the disease's most common form, Duchenne muscular dystrophy, which affects one in 3,500 male births, according to the National Institute of Neurological Diseases and Stroke. Inheritance is linked to the X chromosome and recessive, so the disease primarily affects boys. Most children with Duchenne muscular dystrophy die in their late teens or early 20s. The disease currently has no cure.

"We have identified a new rationale for treating muscular dystrophy, aimed at correcting the devastating effects of a single flawed gene," said Puri. "This is a significant advance over the use of steroids--currently the only treatment available--which offers palliative relief, often with severe side effects."

"These exciting results, while encouraging, will require extensive investigation to determine whether the effectiveness of these drugs in dystrophic mice will translate into an effective treatment for individuals suffering this disease," cautions Puri, who has devoted over 10 years to the study of muscular dystrophy. "It is difficult to predict how long it will take before these studies will be translated into therapies for human patients."

"Our future studies will focus on understanding precisely how several existing deacetylase inhibitors effect muscle regeneration. We will use this information to identify new compounds with similar or even better efficacy in treating muscular dystrophies."

Puri's research on the effects of deacetylase inhibitors on muscle regeneration was inspired by his previous studies, which started 10 years ago, in collaboration with Dr. Vittorio Sartorelli at NIH, on the biochemical and molecular mechanism regulating the expression of genes that coordinate muscle regeneration. These studies led to the identification of different enzymes (called acetyltransferases and deacetylases) that promote or inhibit the expression of regeneration genes, and have the potential of influencing the efficiency of muscle regeneration.


Dr. Puri's colleagues contributing to this study include Giulia Minetti, Chiara Mozzetta and Silvia Fortuni of the Dulbecco Telethon Institute, Rome, Italy; Carlo Serra of the Burnham Institute for Medicine; Claudia Colussi, Stefania Straino, Carlo Gaetano and Maurizio Capogrossi of the Istituto Dermopatico dell' Immacolata, Rome, Italy; Raffaella Adami, Valeria Parente and Roberto Bottinelli of the University of Pavia, Italy; Maurizio Sampaolesi of the Stem Cell Research Institute, Milan, Italy; Monica Di Padova and Vittorio Sartorelli of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland; Barbara Illi of the IRCCS, Milan, Italy; and Paola Gallinari and Christian Steinkühler of the Istituto di Ricerche di Biologia Molecolare, Rome, Italy.

This study was supported with funding from the Muscular Dystrophy Association (MDA), Telethon (Italy), and Parent Project Muscular Dystrophy.

About Burnham Institute for Medical Research
The Burnham Institute for Medical Research is an independent non-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge in life-science and medicine, and providing the foundation for tomorrow's innovative therapies. The Burnham is home to three major research centers: the Cancer Research Center, sponsored by the National Cancer Institute, the Del E. Webb Neuroscience & Aging Research Center, focusing on degenerative diseases associated with aging, and the Infectious & Inflammatory Disease Center. During its 30-year history, discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disease, heart disease, and cancer. Today the Burnham employs nearly 750 persons, including more than 550 scientists, operating with an annual budget of ~$90 million. The majority of the Burnham's funding is derived from competitive research grants, but private philanthropic support is essential to advancing the medical research mission of the organization. For additional information about the Burnham and ways to support its research efforts, visit

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