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.
Nancy Beddingfield | EurekAlert!
Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT
Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine