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【drug-news】实验性抗肿瘤药治疗肌肉萎缩症病人
Normal muscle function restored in dystrophic mice
(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.
### 认领了 实验性抗肿瘤药治疗肌肉萎缩症病人的肌肉推行性病变
营养不良的老鼠恢复了正常的肌肉功能
（La Jolla, CA ——2006年9月17日）在伯明翰研究所正在进行一项研究，即：一种经典的药物可以治疗肌肉萎缩症病人的肌无力和纤维变性，目前正在研究改药的抗肿瘤效应。
该报道为组蛋白脱乙酰基酶抑制剂类药物的潜在应用价值提供了光明前景，这些药物可以促进营养不良的肌肉再生和修复，因此，在两种不同的肌肉萎缩症老鼠模型中缓解了病情的进展。该研究由伯明翰研究所助理教授Lorenzo Puri博士领导，并与罗马DTI和意大利国立卫生研究所合作。全球范围研究者的努力促使该研究于2006年9月17日在Nature Medicine网站发表。
Puri的研究队伍发现运用脱乙酰基酶抑制剂曲古抑菌素A治疗目前正在研究的乳腺癌，可以恢复骨骼肌的质量和阻止肌肉萎缩症的功能不全。重要的是，这些恢复的肌肉可以增加抗收缩的能力，在进行性假肥大性肌营养不良和相关的营养不良中，这是肌肉功能衰弱的最初机制。
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作者:admin@医学,生命科学 2011-09-01 17:13
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