Compound allows cells to bypass gene defects
Forcing ribosomes to ignore inappropriate signals could lead to new treatments for inherited diseases such as Duchenne muscular dystrophy and cystic fibrosis, a new study suggests (Nature 2007;447:87).
Between 5 and 70 per cent of the individual cases of most inherited diseases
are caused by nonsense mutations, which result in premature “stop” codons
and non-functional proteins. Studies suggest that boosting synthesis
of functional proteins in patients with some inherited diseases to as
little as 5 per cent of normal levels could eliminate the principal symptoms
of the disease.
The authors screened around 800,000 low molecular weight compounds and
found that one, PTC124, inhibited reading of premature, but not normal,
termination codons. In addition, they discovered, PTC124 promoted production
of dystrophin in human muscle cells — deficiency of dystrophin
is one of the root causes of muscular dystrophy.
“Clinical trials of PTC124 have been initiated and their successful
completion may ultimately allow therapy of subsets of patients in a large
and diverse
group of genetic disorders,” the authors says.
“As such, this approach is among the first to test the model of personalised
medicine, in which the focus shifts from treatment of a disease to treatment
of a specific genetic defect,” they add.
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