Friday, May 04, 2007

Treatments for some Mendelian diseases in the works?   posted by p-ter @ 5/04/2007 09:58:00 AM

One of the most consistent complaints about medical genetics research is that it's great at finding the gene/genes underlying a disease, but finding the gene/genes doesn't necessarily lead to any sort of treatment. The genes for cystic fibrosis and Duchenne muscular dystrophy, for example, were both identified in the late '80s. Both remain uncured. In fact, the genes underlying a large number of so-called "Mendelian" diseases (named because they are essentually due to defects in a single gene, unlike "complex" or "multifactorial" diseases) were identified in a mad rush after the realization in 1980 that disease genes could be found without knowing anything a priori about a disease or its genetics. As far as I know, no treatments have come out of these studies.

But as they say, Rome was not built in a day. If the precise genetic defect underlying a disease can be indentified, someone will find a way to fix it, though it may take many years, new technologies, and a lot of luck. So it's heartening to see a report in this week's Nature on the identification of a compound that may one day be a treatment for disorders caused by nonsense mutations (mutations that cause a truncated protein). From the abstract:
Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons.
The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.
Clinical trials have apparently been initiated; this is a story to watch.

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