Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Treatment approach to human Usher syndrome: Small molecules ignore stop signals

01.07.2011
New treatment approach shall soon be ready for use in Usher syndrome patients

Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous.

In the most severe cases, patients are born deaf and begin to suffer from a degeneration of the retina in puberty, ultimately resulting in complete blindness. These patients experience major problems in their day-to-day life.

While hearing loss can be compensated for with hearing aids and cochlea implants, it has not proven possible to develop a treatment for the associated sight loss to date. Researchers at Johannes Gutenberg University Mainz (JGU) in Germany have now developed a new treatment approach to this disease.

In previously conducted research into this subject, the research team headed by Professor Uwe Wolfrum of the Institute of Zoology at Mainz University had already gained insight into of the fundamental molecular processes and mechanisms causing this debilitating syndrome. Using the results of this successful basic research, the Usher treatment team in Mainz headed by Dr Kerstin Nagel-Wolfrum has now evaluated potential ocular treatment options.

Their attention was focused on a mutation identified in a specific German family known to develop the most severe form of Usher syndrome. This mutation is a so-called nonsense mutation in the USH1C gene, which leads to the generation of a stop signal in a DNA base, resulting in premature termination of protein synthesis.

The Mainz research team has now published its latest work on pharmacogenetic strategies for the treatment of Usher syndrome patients with nonsense mutations in the May edition of the journal "Human Gene Therapy". The researchers were able to show that a small molecule known as PTC124 (Ataluren®) causes the stop signal in the mutated USH1C gene to be ignored, thus resulting in continuing protein synthesis and the formation of the functional genetic product in cell and organ cultures. In addition to its ability to cause readthrough of stop signals, the active agent PTC124 has also been demonstrated to be highly compatible with murine and human retina cultures. Moreover, the team managed for the first time to demonstrate readthrough of an eye mutation codon in vivo.

"PTC124 is already being tested in clinical trials for its efficacy in treating other diseases involving nonsense mutations, such as cystic fibrosis and Duchenne muscular dystrophy. We therefore hope that this treatment approach will soon be ready for use in Usher syndrome patients," explains Dr Kerstin Nagel-Wolfrum.

Currently putting the finishing touches on his doctoral thesis, Tobias Goldmann is comparing the efficiency of the readthrough rate and the biocompatibility of other molecules that induce the readthrough of nonsense mutations. The focus is particularly on modified aminoglycosides, i.e. derivatives of commercially available and clinically tested antibiotics. These are being designed and synthesized by an Israeli cooperation partner, Professor Timor Bassov of the Haifa Technicon, and have already been successfully used by researchers in Mainz for readthrough of nonsense mutations in Usher genes. In addition to conducting further preclinical studies of the ocular applications of these new substances, the Usher laboratory in Mainz is planning to use this new method of treating this specific form of Usher syndrome in hospital patients as soon as possible.

The translational biomedical research on readthrough of nonsense mutations aimed at developing a treatment for Usher syndrome is being funded by the FAUN foundation and the "Syscilia" project of the Seventh Framework Program of the European Union. It is part of the Research Training Group 1044 "Developmental and Disease-Induced Modifications of the Nervous System," funded by the German Research Foundation (DFG). The group has recently joined the Translational Neurosciences Research Focus of Johannes Gutenberg University Mainz.

PUBLICATIONS:

Goldmann T., Overlack N., Wolfrum U., Nagel-Wolfrum K. (2011): PTC124-Mediated Translational Readthrough of a Nonsense Mutation Causing Usher Syndrome Type 1C. Human Gene Therapy 22:537-547.

DOI: 10.1089/hum.2010.067

Goldmann T., Rebibo-Sabbah A., Overlack N., Nudelman I., Belakhov V., Baasov T., Ben-Yosef T., Wolfrum U., Nagel-Wolfrum K. (2010): Beneficial Read-Through of a USH1C Nonsense Mutation by Designed Aminoglycoside NB30 in the Retina. Investigative Ophthalmology & Visual Science 51:6671-80.

DOI: 10.1167/iovs.10-5741

Petra Giegerich | idw
Further information:
http://www.uni-mainz.de/eng/14329.php
http://www.ag-wolfrum.bio.uni-mainz.de

More articles from Life Sciences:

nachricht Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin

nachricht Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>