Showing posts with label retinitis pigmentosa (RP). Show all posts
Showing posts with label retinitis pigmentosa (RP). Show all posts

Friday, September 28, 2012

Chemical makes blind mice see; compound holds promise for treating humans

The chemical, called AAQ (see below structure,   acrylamide- azobenzene - quaternary ammonium),  acts   by taking the remaining, normally "blind" cells in the retina  sensitive to  light,  said  lead  researcher  Richard Kramer, UC Berkeley professor of molecular and cell biology.   AAQ is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates these neurons much the way rods and cones are activated by light.

The blind mice in the experiment had genetic mutations that made their rods and cones die within months of birth and inactivated other photopigments in the eye. After injecting very small amounts of AAQ into the eyes of the blind mice, Kramer and his colleagues confirmed that they had restored light sensitivity because the mice's pupils contracted in bright light, and the mice showed light avoidance, a typical rodent behavior impossible without the animals being able to see some light. Kramer is hoping to conduct more sophisticated vision tests in rodents injected with the next generation of the compound.

Because the chemical eventually wears off, it may offer a safer alternative to other experimental approaches for restoring sight, such as gene or stem cell therapies, which permanently change the retina. It is also less invasive than implanting light-sensitive electronic chips in the eye.

"The advantage of this approach is that it is a simple chemical, which means that you can change the dosage, you can use it in combination with other therapies, or you can discontinue the therapy if you don't like the results. As improved chemicals become available, you could offer them to patients. You can't do that when you surgically implant a chip or after you genetically modify somebody," Kramer said........... 

Friday, July 30, 2010

Valproic Acid Shown to Halt Vision Loss in Patients With Retinitis Pigmentosa...

Researchers at the University of Massachusetts Medical School (UMMS) believe, they may have found a new treatment for retinitis pigmentosa (RP), a severe neurodegenerative disease of the retina that ultimately results in blindness. One of the more common retinal degenerative diseases, RP is caused by the death of photoreceptor cells. RP typically manifests in young adulthood as night blindness or a loss of peripheral vision and in many cases progresses to legal blindness by age 40. Dr. Shalesh Kaushal,  chair of ophthalmology and associate professor of ophthalmology and cell biology at UMMS, and his team, describe a potential new therapeutic link between valproic acid and RP, which could have tremendous benefits for patients suffering from the disease. In a retrospective study, valproic acid -  approved by the FDA to reduce seizures, treat migraines and manage bipolar disorder -- appeared to have an effect in halting vision loss in patients with RP and in many cases resulted in an improved field of vision. Results from this study, in conjunction with prior in vitro data, suggest valproic acid may be an effective treatment for photoreceptor loss associated with RP.

UMass Medical School will be the coordinating site for a $2.1 million, three-year clinical trial funded by the Foundation Fighting Blindness/National Neurovision Research Institute quantifying the potential of valproic acid as a treatment for RP. The clinical trials will build upon Kaushal's work in the retrospective study in which patients were treated off-label with doses of valproic acid ranging from 500mg to 750mg per day over the course of two to six months. Treated at a time when patients normally experience rapid vision loss as a result of RP, five of the seven patients in the study experienced improvement in their field of vision.
"Inflammation and cell death are key components of RP," said Kaushal. "It appears the valproic acid protects photoreceptor cells from this. If our observations can be further substantiated by randomized clinical trials then low dose valproic acid could have tremendous potential to help the thousands of people suffering from RP."

Dr. Kaushal and colleagues, having previously demonstrated the use of the small molecule, retinoid, as a pharmacological agent capable of increasing the yield of properly folded RP rhodopsins, began screening other small molecules for similar attributes. Because of its already known qualities as a potent inhibitor of the inflammatory response pathway and cell death, valproic acid was believed to have a unique profile making it a potential candidate as a retinal disease treatment...