Transcript Proof of Principal, Medical Therapy and Clinical Trials

What Clinical Trials Can We
Expect for RD in the Future?
Groups of investigators are now working
on several of the Rare Diseases to
move to Trials.
1) Leber Disease: Three groups have
started Clinical Trials on Gene
Replacement Therapy for a form of
LCA. At least one other group also is
planning an LCA Trial.
Future Clinical Trials
2) Stargardt Disease: Dr. Rando
Allikmets and coworkers are working
on Gene Replacement Therapy of the
mutated gene in a rodent model of
Stargardt Disease. So far, the results
are preliminary but good and, if finally
positive for safety and efficacy, a
Clinical Trial is planned.
Other research groups are working on
similar Gene Therapy efforts for
Stargardt Disease.
Future Clinical Trials
3) Usher Disease: Research groups are
working on both Usher 1 and Usher 3
to replace the mutated genes in the
two conditions through Gene Therapy.
• Producing good animal models in both
conditions has been a problem that is
currently being overcome.
• Progress is being made as reported by
Dr. Flannery
Future Clinical Trials
4) Choroideremia: Scientists are close to
producing a good rodent model for
Choroideremia. They will then use
Gene Therapy to replace the mutated
gene in the model. If successful, a
human Clinical Trial can be planned.
5) Similar Gene Replacement is planned
for some of the other Rare Diseases
such as Retinoschisis.
What about AMD?
CURRENT AMD TREATMENTS
Dry AMD – nutrition therapy. The
antioxidants studied in the AREDS
clinical trial of the NEI are available.
Wet AMD – several drugs now have been
approved by government agencies in
many countries to slow the growth of
new, abnormal blood vessels. The best
known is Lucentis.
Nutrition and AMD
AREDS Antioxidant Treatment
A Clinical Trial for antioxidants in treating AMD
has been completed by the National Eye
Institute. It was called the Age-Related Eye
Disease Study (AREDS).
It found that some nutritional supplements
helped in AMD. The antioxidant nutrients
studied were B-carotene and vitamins C and
E along with the mineral zinc.
The antioxidants only slow the course of the
disease at a specific (mid) stage of AMD.
The antioxidants are available for sale although
a physician should be consulted before using
them.
Clinical Treatments –
Wet AMD
• Lucentis – Genentech has an agent,
“Lucentis” for wet AMD. Lucentis is an
antibody that works against VEGF, a small
protein that calls in the new, abnormal blood
vessels. Lucentis actually improves vision.
• One of the problems with Lucentis though is
that it must be injected into the eye.
• Also, there usually have to be repeat
injections.
• Another problem is the high cost but a similar
agent, Avastin, is available at much lower
cost.
AMD Clinical Trials –
Gene Therapy Trial
• GenVec is conducting a Gene Therapy
Clinical Trial for wet AMD. It delivers the
PEDF gene into the eye. Phase 1 of the Trial
is completed and the safety results are very
good.
• PEDF is a natural protein that has both
antineovascular and neuron-survival
properties. Thus, it could be used for both
AMD and RP.
• If the results on wet AMD are positive,
GenVec could then move on to the use of
PEDF in RP and in dry AMD along with wet
AMD.
Clinical Trials – Wet AMD
Several other agents are being tested as
anti-neovascular agents. For example:
• The company Oxigene has an agent,
Combretastatin, that they have used as an
antineovascular agent in cancer.
• It is now in a Clinical Trial for wet AMD.
• This drug can be delivered to the eye through
the blood so is fairly safe.
• Other similar agents are being developed.
AMD Clinical Trials - Nutrition
• A Nutrition Trial called AREDS2 with lutein is
underway in AMD patients at the NEI.
• Lutein/Zeaxanthin are carotenoids, the
colored pigments in fruits and vegetables,
that are concentrated in the human retina –
especially the macula. It is thought that they
act as antioxidants and thus protect
photoreceptor cells from oxidative damage.
• This Trial will take several years though to
complete.
• Until then, take your mother’s advice and
“Eat your fruits and vegetables!”
In Conclusion….
Several Clinical Trials are planned or are
already in progress for different types of RD
therapies.
For example, Gene Therapy work in RP animal
models shows not only sight restoration but
a long term, positive effect. Is this a “cure”?
• Other basic work in the fields of gene
therapy, stem cell research, pharmaceutical
therapy, nutrition and electronic implants
shows promise with several Clinical Trials in
progress.
• The retinal prosthetic device could be the
best hope for sight restoration for patients
with advanced retinal degeneration.
A Final Thought…..
• We can treat and, in some cases,
maybe even cure diseases in many
animal models of retinal degeneration.
• Many human Clinical Trials are starting
such that treatments are coming soon.
• These are expensive and time
consuming….. but who can put a price
on restoring sight?