Drug Restores Vision in Retina without Functional Photoreceptors

April 04, 2014

Foundation-funded researchers from the University of California (UC), Berkeley are making significant progress in the development of a drug that holds potential for restoring vision in people blind from a wide range of advanced retinal diseases. Known as DENAQ, the compound provided vision to blind mice lacking functional photoreceptors, the cells that are  normally responsible for eyesight. Results of the study were published in the journal Neuron

DENAQ works by bestowing light sensitivity to retinal ganglion cells — cells that survive after photoreceptors die off from retinal degenerative conditions such as retinitis pigmentosa. 

“The idea we have is to develop chemicals that can impart light sensitivity in the remaining cells in the retina,” says Richard Kramer, Ph.D., the study’s lead investigator. “Those cells can send electrical signals back to the brain to provide some level of vision.”

A major advantage of DENAQ is that it works independent of the genetic mutation causing a person’s vision loss. A patient won’t likely need to knowhis or her disease-causing gene to use the drug.  

Dr. Kramer says that DENAQ is a big step forward, because it provides many benefits over AAQ, a chemical his team studied previously for vision restoration. They found that AAQ works only in very bright light and for just a few hours. In contrast, DENAQ works in typical daylight, and a single dose lasts for about a week. In the future, by using slow-release drug-delivery polymers being developed by other scientists, Dr. Kramer believes a single ocular injection of DENAQ will last much longer.

What came as a complete surprise was that DENAQ had no effect on cells in healthy retinas, only in retinas with disease. “We learned that there’s something special that happens to ganglion cells in the degenerating retina that makes them responsive to the chemical,” says Dr. Kramer. “We stumbled upon this completely by accident.”  

“The reason this is of interest is that blinding retinal diseases start off as regional patterns of vision loss — they progress,” explains Dr. Kramer. “Our hope is that the chemical will act only where the disease is ongoing and not interfere with a patient’s remaining vision from parts of the retina that are still healthy.” 

DENAQ and similar opto-pharmacological treatments confer additional benefits over other therapeutic options. Unlike a gene therapy or stem- cell treatment which can’t be easily adjusted or stopped, DENAQ dosing can be easily modified — increased, decreased or discontinued — depending on the needs of the individual patient. 

The biggest unknown is what a patient might see when treated with DENAQ. Lab studies indicate that treated mice are showing behavioral responses to light, but it is difficult to know exactly what they are seeing. 

Dr. Kramer believes that DENAQ by itself will not be sufficient to provide vision under all lighting conditions. “Some vision -enhancement device, such as a pair of high-tech goggles, may be required, perhaps to increase the brightness or change the contrast,” says Dr. Kramer. “Also, DENAQ operates slower than photoreceptors, so we may need the goggles to slow down movement and perhaps simplify the image of the visual world.”

UC Berkeley is receiving $400,000 over three years from the Foundation to develop DENAQ and similar compounds. The grant will also be used to assess safety to position the treatment approach for evaluation in a future clinical trial. Dr. Kramer notes that the U.S. Food and Drug Administration is primarily concerned with safety in authorizing a human study for a potential therapy.