Present and Future Treatments for Retinal Degenerative Diseases: An Overview

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Present and Future Treatments for Retinal
Degenerative Diseases An Overview

• Gerald J. Chader
• Doheny Retina Institute
• USC Medical School
• Los Angeles, CA

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The NeedsTreatment Availability

• No generally effective treatment is yet available
  for Retinitis Pigmentosa or allied diseases such
  as Usher Syndrome (deaf-blindness). Vitamin A
  suipplements might help some.
• Similarly, no effective treatment other than
  nutritional supplements is available for the
  millions with dry AMD.
• Treatment is available for wet AMD but it is
  expensive and often must be repeated.

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Current and Future Treatments

• All treatments will not benefit all RP or AMD
  patients.
• Thus, treatments must be divided into 2
  categories
• 1) treatments used when some photoreceptors
  remain alive and functional. These treatments
  prolong the life of the photoreceptor cell.
• 2) treatments used when photoreceptors are
  dead and need to be replaced.
• Luckily, we have good clinical techniques like
  OCT to distinguish between these 2 conditions.

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Current and Upcoming RP Clinical Trials

• First, lets consider three possible treatments
  where the patient yet has viable photoreceptor
  cells in their retina.
• These are 1) Gene Therapy
• 2) Pharmaceutical Therapy
• 3) Nutritional Therapy

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1) Gene Replacement Therapy

• Gene Therapy is the replacement of a defective
  (mutated) gene such that an important protein
  (e.g., enzyme) is present again in the cell. With
  this, the photoreceptors function better and live
  longer.
• In Gene Therapy, a modified viral vehicle (called
  a vector) is used to bring a normal,
  replacement gene into the cell.
• Since it is estimated that about half of the RD
  gene mutations are known for humans, we have the
  theoretical possibility of replacing many of
  these genes in the future and helping many
  patients.

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Gene Replacement Therapy

• Starting in the 90, several groups showed that
  they could replace defective genes in animal
  models affected by RP and partially restore
  visual function. For example
• In 2001, a group of scientists reported good
  restoration of visual function in a dog model for
  Lebers disease. Even now, about 7 years later,
  the dogs first treated are still seeing very
  well. Other dogs have more recently been treated
  and the results are excellent.
• Clinical Trials for Gene Replacement Therapy in
  LCA have begun in London and Philadelphia. Other
  trials are planned around the world.
• No results on safety or efficacy have yet been
  reported but the initial results seem to be good.

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2) Pharmaceutical Therapy

• Pharmaceutical Therapy is the use of an agent
  that will prolong the life and function of a
  photoreceptor cell.
• Some agents available are natural proteins found
  in the body that are called neuron-survival
  agents. Some other agents are man-made drugs
  that function similarly.
• In 1990, it was shown that the natural growth
  factor, bFGF, could delay photoreceptor cell
  degeneration in an animal RP model.
• Since then, many natural factors found in small
  amounts in brain, retina and other tissues have
  been shown to slow photoreceptor cell death when
  delivered to the retinas of RD animal models.

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Pharmaceutical TherapyClinical Trials

• There are currently two Pharmaceutical Clinical
  Trials underway. One in RP patients and one in
  dry AMD patients. These Trials are testing a
  neuron-survival agent called CNTF.
• The company Neurotech has a special tiny capsule
  that can be implanted within the eye that
  produces the CNTF. The CNTF then diffuses to the
  retina where it helps remaining photoreceptor
  cells to survive and even function better.
• If the trials are successful, this will probably
  be the first treatment generally available to RP
  and dry AMD patients.

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Neurotech Clinical Trial

• The Neurotech device with CNTF was well tested in
  an animal model of RP and found to be very
  effective in slowing the degeneration.
• The safety results of Phase 1 of Neurotechs
  Clinical Trial are excellent. In 3 of 10 RP
  patients tested, even some improvement in vision
  was noted.
• Based on these results, there are high
  expectations for positive efficacy results from
  the Phase 2 and 3 parts of the Trials.
• Keep in touch with R.I. for updates!

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3) Nutrition For RP

• The use of nutrition as a therapy in RP is
  controversial but now must be taken seriously in
  prevention or at least slowing down the
  degenerative process.
• In 1993, Dr. Eliot Berson found that vitamin A
  supplementation slows RP to a small extent in
  some patients. On the other hand, Vitamin E was
  found to be harmful.
• Thus, the oral use of vitamin A has been the only
  treatment available to date to RP patients.
• BUT due to the small effect in only some
  patients, some Ophthalmologists do not recommend
  the treatment.

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Another Trial for Vitamins A E

• To better test the possible helpful effects of
  Vitamin A on RP and to determine whatever vitamin
  E does (good or bad), another trial was started.
• It is now complete although the results have not
  been announced.
• The trial tested vitamins A and E alone or in
  combination to assess their effects on the
  progression of RP.
• Keep in touch with R.I. for news!

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Antioxidants slow photoreceptor cell death in RP

• Recently, Prof. Theo van Veen reported that the
  use of antioxidants was very effective in slowing
  the disease course in a rodent model of RP.
• Using sophisticated techniques, he showed that
  severe oxidative damage occurred in the retinal
  photoreceptor cells preceding cell death in the
  model of RP.
• BUT, supplementation with a specific cocktail of
  antioxidants greatly reduced the oxidative damage
  and slowed photoreceptor cell death both rods
  and cones.
• Importantly, the supplements were given by mouth
  to the animals. No injection is needed.

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Upcoming Nutritional Clinical Trial

• A clinical trial has now begun to test the
  effectiveness of the antioxidant agents in
  humans.
• This trial is in Spain sponsored by Dr. F.J.
  Romero and will probably take 2 years or more to
  complete.
• BUT, the supplement is already available for
  purchase over the internet it is called
  RetinaComplex.
• It is probably safe since the supplement
  ingredients are classified by the US FDA as safe
  nutrients rather than untested drugs.