Emerging Treatment Gets the Message Right

July 07, 2011

In every cell in our body, DNA is sending messages, known as mRNA, which tell our cells what proteins to make. Proteins are vital to our health, because they: provide our bodies with structure and strength; regulate and protect our body’s chemistry; and are involved in the transport of oxygen and other essential substances. Proteins are also essential to the health of our photoreceptors and the biochemical process that makes vision possible. Hence, it is critical that the messages transmitted by our DNA are translated correctly, so that the right proteins are made.

In about 12 percent of all retinal degenerative diseases, the translation of mRNA stops prematurely leading to the production of nonfunctional proteins. In simple terms, it’s as if someone stops reading a sentence halfway through, and the resulting message doesn’t make sense. These translational errors are known as premature termination codons or PTCs.

In a Foundation-funded study at the Johannes Gutenberg University in Mainz, Germany, Uwe Wolfrum, Ph.D., and his team are evaluating a drug that can “read through” PTCs in retinal cell cultures and mouse models of Usher syndrome type 1C (USH 1C). The drug enables the cell to read the complete message and make the right protein. Known as PTC124, the drug has already shown some effectiveness in clinical trials for Duchene muscular dystrophy and cystic fibrosis, both of which are devastating conditions caused by PTCs.

In a research paper published in the journal Human Gene Therapy, May 2011, Dr. Wolfrum reported that PTC124 was effective in initial USH 1C studies. He notes that in moving the treatment forward, his team needs to identify the optimal method for delivering the drug to the retinas in humans. They will evaluate a variety of administration options including oral delivery, eye drops, and subretinal injections. As with any new drug, safety studies are essential, as well; it is important to verify that the drug doesn’t cause problems in other parts of the body.

“We are excited about this innovative drug, because it holds potential for treating a wide range of retinal conditions including forms of retinitis pigmentosa and Usher syndrome,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “The fact that it has shown some success in clinical trials for other diseases is also a big plus. That gives us more confidence in the drug as we move it forward.”

Dr. Wolfrum’s team recently received a three-year grant from the Foundation to conduct safety, effectiveness, and delivery studies for PTC124 and improved versions of the drug.