Modified antibiotics could treat genetic diseases

7 May 2009

By modifying the properties of the common antibiotic gentamicin, researchers at the Technion-Israel Institute of Technology have developed what could become an effective treatment for many human genetic diseases, including cystic fibrosis (CF), Duchenne muscular dystrophy, Usher Syndrome and numerous cancers. The findings have been published in the Journal of Medicinal Chemistry.

Gentamicin belongs to a class of antibiotics called aminoglycosides, which are used to treat a wide range of bacterial infections. Studies have shown that gentamicin can counteract genetic diseases, including those mentioned above that occur when mutations cause disruptions of the development processes of proteins.

The drug enables ribosomes (the structures within a cell that carry out protein synthesis) to ignore these disruptions and instead generate healthy, full-length functional proteins.

But using gentamicin to treat these diseases requires much higher doses than those commonly prescribed for bacterial infections. At these higher doses gentamicin is non-selective and extremely toxic to humans, with irreversible hearing loss (ototoxicity) being the main negative consequence.

In search of a way to bypass these complications, the team led by Professor Timor Baasov of the Technion Faculty of Chemistry modified existing aminoglycoside antibiotic drugs, and carefully monitored biological and toxicity tests of the resulting derivatives. The result is “NB54,” a new (and patented) chemical derivative of gentamicin.

“We’ve created a new purpose for aminoglycosides by removing their traditional, natural actions as antibiotics,” said Baasov. “The loss of their antibacterial activity makes them highly selective, less toxic, and allows for their use in repairing ‘wrong’ genes in human beings.”

So far, the researchers have observed the action of NB54 in ex vivo cell lines. They are currently awaiting data from animal model testing.

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