Transcript Proof of Principal, Medical Therapy and Clinical Trials

Present and Future Treatments
for Retinal Degenerative
Diseases: An Overview
Gerald J. Chader
Doheny Retina Institute
USC Medical School
Los Angeles, CA
The Needs:
Treatment Availability
• No generally effective treatment is yet
available for Retinitis Pigmentosa or allied
diseases such as Usher Syndrome (deafblindness). 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.
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.
Current and Upcoming
RP Clinical Trials
First, let’s 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
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.
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 Leber’s 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.
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 “neuronsurvival agents”. Some other agents are manmade 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.
Pharmaceutical Therapy:
Clinical 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.
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 Neurotech’s
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!
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.
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!
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.
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”.