Post by ddrahal on Apr 25, 2007 1:31:30 GMT -5
Please read this article on DMD USA and look to hear your comments if this drug would help any form of Duchenne
April 22, 2007
NEW DRUG RESTORES NORMAL
MUSCLE FUNCTION IN ANIMALS WITH MD
TUCSON, Ariz., April 22, 2007 — Researchers have for the first time used a drug to restore normal muscle function in a mouse model of the most common childhood form of muscular dystrophy, raising hopes ahead of the release of data from a trial in patients with the disease, the Muscular Dystrophy Association announced today.
“These results in the animal model of Duchenne muscular dystrophy (DMD), coming out just before the release of the data from the human clinical trial, justify our hope that PTC124 will turn out to be the first effective treatment for any form of muscular dystrophy,” said Dr. Valerie Cwik, vice president of research and medical director of MDA, which helped fund both the animal studies and the human trial..
PTC124, discovered and developed by PTC Therapeutics of South Plainfield, N.J., overrides a type of genetic flaw called a nonsense mutation (also known as a premature stop codon), the cause of some 15 percent of human cases of DMD. The study showed that the drug also worked to treat human muscle cells containing premature stop codon mutations that were cultured in laboratory dishes.
The “proof of principle” demonstrated in both human cell lines and in an animal model offers a wide-ranging potential for PTC124 to treat over 1,800 genetic diseases for which a small percentage of cases are due to stop codon mutations, including other forms of muscular dystrophy.
“We could not detect the changes in force due to damage cause by exercise that we typically find in animals with the disease,” said Lee Sweeney, chairman of the Department of Physiology at the University of Pennsylvania School of Medicine in Philadelphia and co-senior author on the paper published online today by Nature that describes these findings. “For all intents and purposes, these mice looked like normal animals by this key measure.” Other less direct measures also showed improvement.
Nonsense mutations cause cells to stop reading genetic instructions that underlie protein synthesis too soon, leading to production of a short, nonfunctional protein.
In DMD, that protein is dystrophin, which helps protect the membrane surrounding each muscle fiber from being damaged during muscle contractions.
Dystrophin-deficient, DMD-affected mice that received PTC124 by a combination of oral feeding and/or injections were stronger and showed less contraction-related muscle damage than is characteristic of these mice.
Blood levels of an enzyme called creatine kinase, which leaks out of damaged muscle cells, dropped significantly compared to those of untreated mice, indicating many more muscle cells remained intact.
Tests showed the treated mice produced about 20 percent to 25 percent of the normal level of full-length dystrophin, and that the dystrophin was in its normal place in the muscle fiber membrane.
Of equal importance, the investigators found no evidence of “off-target” effects from PTC124. Cells appeared to read properly positioned stop codons in other genes normally.
No toxicity of any kind was observed in the DMD-affected mice.
ABOUT PTC THERAPEUTICS INC.
PTC is a biopharmaceutical company focused on the discovery and development of orally administered, proprietary, small-molecule drugs that target post-transcriptional control processes. Post-transcriptional control processes regulate the rate and timing of protein production and are of central importance to proper cellular function. PTC’s internally discovered pipeline addresses multiple therapeutic areas, including genetic disorders, oncology and infectious diseases. In addition, PTC has developed proprietary technologies and extensive knowledge of post-transcriptional control processes that it applies in its drug discovery and development activities, including the Gene Expression Modulation by Small-molecules (GEMS) technology platform, which has been the basis for collaborations with leading pharmaceutical and biotechnology companies such as Pfizer, CV Therapeutics and Schering-Plough.
ABOUT THE MUSCULAR DYSTROPHY ASSOCIATION
MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education.
ABOUT DUCHENNE MUSCULAR DYSTROPHY
Duchenne muscular dystrophy (DMD) is a progressive muscle disorder that causes the loss of both muscle function and independence. DMD is the most prevalent of the childhood muscular dystrophies, and usually results in death by age 30. Each year, approximately 20,000 children worldwide are born with DMD (one of every 3,500 male children).
April 22, 2007
NEW DRUG RESTORES NORMAL
MUSCLE FUNCTION IN ANIMALS WITH MD
TUCSON, Ariz., April 22, 2007 — Researchers have for the first time used a drug to restore normal muscle function in a mouse model of the most common childhood form of muscular dystrophy, raising hopes ahead of the release of data from a trial in patients with the disease, the Muscular Dystrophy Association announced today.
“These results in the animal model of Duchenne muscular dystrophy (DMD), coming out just before the release of the data from the human clinical trial, justify our hope that PTC124 will turn out to be the first effective treatment for any form of muscular dystrophy,” said Dr. Valerie Cwik, vice president of research and medical director of MDA, which helped fund both the animal studies and the human trial..
PTC124, discovered and developed by PTC Therapeutics of South Plainfield, N.J., overrides a type of genetic flaw called a nonsense mutation (also known as a premature stop codon), the cause of some 15 percent of human cases of DMD. The study showed that the drug also worked to treat human muscle cells containing premature stop codon mutations that were cultured in laboratory dishes.
The “proof of principle” demonstrated in both human cell lines and in an animal model offers a wide-ranging potential for PTC124 to treat over 1,800 genetic diseases for which a small percentage of cases are due to stop codon mutations, including other forms of muscular dystrophy.
“We could not detect the changes in force due to damage cause by exercise that we typically find in animals with the disease,” said Lee Sweeney, chairman of the Department of Physiology at the University of Pennsylvania School of Medicine in Philadelphia and co-senior author on the paper published online today by Nature that describes these findings. “For all intents and purposes, these mice looked like normal animals by this key measure.” Other less direct measures also showed improvement.
Nonsense mutations cause cells to stop reading genetic instructions that underlie protein synthesis too soon, leading to production of a short, nonfunctional protein.
In DMD, that protein is dystrophin, which helps protect the membrane surrounding each muscle fiber from being damaged during muscle contractions.
Dystrophin-deficient, DMD-affected mice that received PTC124 by a combination of oral feeding and/or injections were stronger and showed less contraction-related muscle damage than is characteristic of these mice.
Blood levels of an enzyme called creatine kinase, which leaks out of damaged muscle cells, dropped significantly compared to those of untreated mice, indicating many more muscle cells remained intact.
Tests showed the treated mice produced about 20 percent to 25 percent of the normal level of full-length dystrophin, and that the dystrophin was in its normal place in the muscle fiber membrane.
Of equal importance, the investigators found no evidence of “off-target” effects from PTC124. Cells appeared to read properly positioned stop codons in other genes normally.
No toxicity of any kind was observed in the DMD-affected mice.
ABOUT PTC THERAPEUTICS INC.
PTC is a biopharmaceutical company focused on the discovery and development of orally administered, proprietary, small-molecule drugs that target post-transcriptional control processes. Post-transcriptional control processes regulate the rate and timing of protein production and are of central importance to proper cellular function. PTC’s internally discovered pipeline addresses multiple therapeutic areas, including genetic disorders, oncology and infectious diseases. In addition, PTC has developed proprietary technologies and extensive knowledge of post-transcriptional control processes that it applies in its drug discovery and development activities, including the Gene Expression Modulation by Small-molecules (GEMS) technology platform, which has been the basis for collaborations with leading pharmaceutical and biotechnology companies such as Pfizer, CV Therapeutics and Schering-Plough.
ABOUT THE MUSCULAR DYSTROPHY ASSOCIATION
MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases through programs of worldwide research, comprehensive services, and far-reaching professional and public health education.
ABOUT DUCHENNE MUSCULAR DYSTROPHY
Duchenne muscular dystrophy (DMD) is a progressive muscle disorder that causes the loss of both muscle function and independence. DMD is the most prevalent of the childhood muscular dystrophies, and usually results in death by age 30. Each year, approximately 20,000 children worldwide are born with DMD (one of every 3,500 male children).