Scientists evaluate two different strategies to treat Usher syndrome

Published on December 6, 2012 at 1:55 AM · No Comments

The research team has also recently published the latest results of its pharmaco-genetic approach to the treatment of Usher syndrome patients with nonsense mutations in the journal EMBO Molecular Medicine. In this case, Dr. Tobias Goldman and the other team members compared various molecules that can induce read-through of the stop signal and thus provide for normal protein synthesis. In addition, they evaluated the retinal biocompatibility of the various molecules. The research focused on PTC124 (Ataluren-) and 'designer' aminoglycosides. These aminoglycosides are derived from clinically tested antibiotics and have been modified by Professor Dr. Timor Bassov of the Technicon in Haifa/Israel to improve their capacity to read-through the mutation and reduce their toxicity. The Mainz researchers had already been successful in using one of the first generation designer aminoglycosides to read-through the nonsense mutations in the USH1C gene.

They were now able to show that PTC124 (Ataluren-) and a second generation aminoglycoside (NB54) in particular would induce read-through of the stop signal in the mutated USH1C gene. This meant that protein synthesis continued, so that the active gene product was synthesized in the cell and organ cultures. Both active substances, PTC124 and NB54, generally enhanced read-through efficacy and exhibited improved tolerability in mouse and human retinal cultures in comparison with clinically employed antibiotics. The team also successfully documented read-through of the mutation in vivo a mouse model.

"Our gene-based treatment strategies, involving gene repair as well as read-through therapy, represent valuable and promising alternatives to viral gene addition and may actually be the only treatment option for the large and isoform-rich USH genes. We hope that these alternatives will make a significant contribution to the therapy of both Usher syndrome patients as well as others with severe genetic retinal pathologies and other genetic disorders," explains Dr. Kerstin Nagel-Wolfrum.

In addition to continuing its preclinical studies into the use of the active substances, the Mainz Usher research team plans to make its new Usher syndrome therapy available to patients as soon as possible.

Source: Johannes Gutenberg Universitaet Mainz

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