Macular Degeneration and siRNA

Macular degeneration is the leading cause of severe vision loss in people 60 years of age or older in the United States and throughout many parts of the world.

The treatment for macular degeneration listed below is a major accomplishment for two reasons. First, it is a treatment for a disease that is becoming more prevalent as the population ages. Second, the therapy uses the new siRNA technology. This treatment uses a short strand of RNA in a special configuration that turns off a vascularization gene by binding with its RNA. It is the sequence of the siRNA that makes it specific for the endothelial growth factor (VEGF) gene and causes the proteins manufacture to be turned off. The technique is very general so can be applied to almost any gene. I believe that siRNA will bring about a revolution in medicine.

Phase II Trial Starts for siRNA Therapy for Wet AMD
10/19/2005
Acuity Pharmaceuticals initiated a Phase II trial for Cand5, its lead product candidate for the treatment of wet age-related macular degeneration (wet AMD), following successful completion of Phase I trial.
According to the company, this is the first-ever Phase II program for a small interfering RNA (siRNA) therapy, based on the gene silencing technology of RNA interference (RNAi).
Acuity, founded in 2002, has an exclusive license to several types of RNAi intellectual property from the University of Pennsylvania, including both broad-based and target-focused applications.
“Cand5 is safe and well-tolerated in patients with wet AMD,” said Jonathan L. Prenner M.D., of UMDNJ—Robert Wood Johnson Medical School and an investigator for Acuity’s Phase I study.
Cand5’s RNAi mechanism silences the genes that promote the overgrowth of blood vessels that lead to vision loss in wet AMD by shutting down the production of vascular endothelial growth factor (VEGF), which has been shown to be the central stimulus in the development of wet AMD.
By stopping production of VEGF at the source, Cand5 is expected to have efficacy advantages over other types of therapies for wet AMD, which work by inhibiting VEGF only after it has already been produced in the the eye, explained Dale Pfost, Ph.D., president and CEO of Acuity.
“A single molecule of Cand5 repeatedly stops hundreds of VEGF molecules. This sustained duration of action could result in less frequent delivery, perhaps only four to five times per year,” asserted Dr. Pfost.
Acuity’s Phase I trial, an open label, dose-escalation study that included 15 patients, tested five dose levels administered by intravitreal injection at six-week intervals. Cand5 was shown to be safe and well tolerated following repeat administration of the escalating dose levels, up to 3.0 mg per eye.
This study also included a pharmacokinetic analysis indicating that the study drug was not present in the plasma of any of the patients at any of the doses tested. This absence of systemic exposure to Cand5 is signficant since powerful VEGF inhibitors have the potential to cause serious adverse effects if present systemically, notes Dr. Pfost.

Wet Age-Related Macular Degeneration
Wet Macular Degeneration occurs when abnormal blood vessels start to grow on the center of your retina. These new blood vessels may be very fragile and often leak blood and fluid. The blood and fluid can damage your macula or create a scar on your retina, causing vision problems. Damage to the macula can occur rapidly, causing a noticeable loss of central vision. The vision loss from wet macular degeneration may be permanent, because abnormal blood vessels and scar tissue are actually replacing normal retina tissue. Once lost, these light-sensitive cells in your retina cannot be replaced.
An early symptom of wet macular degeneration is vision change, when straight lines appear wavy. For example, you may notice that your door frames appear wavy instead of straight. If you notice this condition or other changes in your vision, contact your eye care professional immediately for a comprehensive dilated eye exam. Treatments are available that may slow and reduce vision loss associated with wet macular degeneration. You should report any changes in vision to an eye care professional as soon as you notice them.
It is estimated that more than 2 million people in the United States currently have wet macular degeneration, with an increase of 200,000 new cases