Progress In Vision Research: The Year in Review
From the Foundation
Fighting Blindness Newsletter
[Genetic Research]
[Gene Therapy]
[Medical Therapy]
[Retinal Cell Transplants]
[The Future]
Back to Main Research Page
Over the past year, Foundation-funded scientists made remarkable
progress toward finding treatments and cures for retinal degenerative
disease. The Foundation's investment in research is beginning to propel
experimental therapies from the laboratory to clinical trial
investigation. We can now glimpse a day when doctors will recruit
patients for clinical trials testing gene therapy, medical therapy and
retinal cell transplantation. While we have our sights set on the
future, it is heartening to recount all of the progress that occurred in
1997.
Genetic Research
In March, a collaborative research team, funded in part by The
Foundation, discovered the gene which causes Stargardt disease.
Stargardt disease is the most common early onset form of macular
degeneration. In September, this same research team reported that
mutations in this gene, known as the ABCR gene, also cause an estimated
16 percent of age-related macular degeneration cases. This stunning
breakthrough provided the first concrete evidence that AMD has a major
genetic component.
In October, Foundation-funded researchers found mutations in two genes
that cause autosomal recessive retinitis pigmentosa. These genes,
called "RPE 65" and "CRALBP", are the first RP genes to be found in the
retinal pigment epithelium (RPE). The RPE is a cell layer that supports
the function of photoreceptor cells in the retina. Researchers have
long speculated that some forms of RP might be caused by gene mutations
in RPE cells. However, almost all of the other genes found to cause RP
are active in photoreceptor cells. The discovery of the RPE 65 and
CRALBP genes should spur closer examination of genes that are active in
RPE cells.
In November, a collaborative research group funded in part by The
Foundation, isolated the first gene found to cause a severe, early onset
retinal degeneration called cone-rod dystrophy. This genetic form of
the disease is clinically known as CORD2 (cone-rod dystrophy 2).
Individuals with cone-rod dystrophy first experience central vision loss
followed by night blindness and peripheral vision loss. Previous
studies of patients thought to have CORD2 found that central vision loss
begins in the first decade of life with the onset of night blindness
occurring sometime after age 20. Little visual function remains after
the age of 50.
The Foundation is deeply committed to finding all of the genes
responsible for these blinding diseases. An understanding of how a
defective gene leads to vision loss is crucial in developing effective
treatments and cures.
Back to the Top of the Page
Gene Therapy
Gene therapy holds tremendous potential for the future treatment of
retinal degenerative diseases. Although much work lies ahead,
researchers are developing treatments that might one day replace
non-functional genes or silence harmful genetic mutations. In a major
breakthrough, scientists have delayed retinal degeneration in a rodent
with rapid onset retinal degeneration by delivering healthy genes to
photoreceptor cells.
This breakthrough demonstrated that gene therapy can work. However,
further success is dependent on refining gene delivery systems that can
transport healthy genes into retinal cells. In scientific jargon, gene
delivery systems are called vectors. Most vectors are genetically
altered viruses. Viruses are extremely effective at infiltrating the
nucleus of a cell. However, viruses also carry harmful genetic
information that evoke immune responses. Immune responses jeopardize
any potential therapeutic value the healthy gene might offer.
Scientists are currently working to genetically alter vectors that will
deliver healthy genes to retinal cells without evoking damaging immune
responses.
Drs. Debora Farber and Rajendra Kumar-Singh of The Foundation's Research
Center at UCLA have developed a promising new vector called an
"encapsidated adenovirus minichromosome" (EAM). This new vector seems
to have eliminated much of the harmful genetic elements of the virus
while still retaining its gene delivery capabilities. Although further
testing is necessary, this vector has shown promise in preliminary
experiments in rodents.
Due to recent progress in gene therapy research, The Foundation will
sponsor a gene therapy symposium in February. The symposium will allow
the world's leading genetic researchers to assess current research and
identify future directions. We will report on this meeting in future
newsletters.
Back to the Top of the Page
Medical Therapy
Over the past year, The Foundation Fighting Blindness, The National Eye
Institute and Regeneron Pharmaceuticals have been coordinating research
efforts to advance survival factor therapies from the laboratory to
human clinical trial investigation. Survival factors are substances
produced by the body that sustain nerve cells. In laboratory research,
a survival factor developed by Regeneron called Axokine has shown the
ability to save degenerating photoreceptor cells and delay their death.
Although further work is needed before Axokine can be tested in
patients, The Foundation and its Scientific Advisory Board think this
experimental therapy has shown enough promise in the laboratory to
warrant consideration of clinical trial testing. The Foundation is
hopeful that survival factors will one day preserve vision in humans.
In the coming year, Foundation researchers will be further testing the
efficacy and safety of Axokine to gain FDA approval for future clinical
trial testing. Partnerships with pharmaceutical and biotechnology
companies, such as Regeneron, are critical in gaining access to new
drugs that might arrest or slow retinal degeneration. Through its
Medical Therapy Program, The Foundation is actively seeking these
partnerships.
Back to the Top of the Page
Retinal Cell Transplantation
In addition to laboratory studies funded by The Foundation, several
research groups have begun performing experimental retinal cell
transplants in humans. In June, The Foundation sponsored a scientific
symposium to evaluate current research. At the symposium, transplant
scientists presented their most recent results.
This meeting was extremely helpful in evaluating transplant research and
identifying future directions. Human transplant research did not show
any clear indication of efficacy either in preventing vision loss or
restoring sight. Immune rejection was identified as a common
complication that must be addressed. However, laboratory research
showed progress in overcoming hurdles still confronting this
experimental treatment modality.
One major laboratory breakthrough concerns the supply of healthy donor
cells. Although helpful for research purposes, neither embryonic nor
adult cells represent an ideal source should transplantation become a
viable treatment option. Clearly, an abundant supply of healthy donor
cells would become critical. One possible source of tissue might be
transformed cells. Transformed cells have the ability to reproduce
themselves in large quantities in culture. Dr. Raymond Lund, a
Foundation-funded scientist from the Institute of Ophthalmology in
London, presented data demonstrating that transformed RPE cells can
delay photoreceptor degeneration when transplanted into a rodent with a
gene defect in its RPE cells.
Although human experiments have not yet demonstrated success, The
Foundation remains optimistic that retinal cell transplantation may one
day offer patients a safe and effective treatment. Clearly, laboratory
research must overcome remaining obstacles to clear the way for future
success in clinical trial research.
Back to the Top of the Page
The Future
As experimental therapies advance to the clinical trial arena, funding
becomes ever more costly. To keep pace with the financial demands of
vision research, The Foundation has embarked on an ambitious plan to
double its funding commitment over the next five years. The Foundation
is also partnering with pharmaceutical and biotechnology companies to
test drugs and agents that may offer therapeutic benefit. Such
relationships are attracting a greater investment in vision research.
In short, The Foundation is committed to the urgent goal of finding
treatments and cures for retinal degenerative disease.
Back to the Top of the Page
Return to Main RP Page
Send
comments to rpmail@jwen.com
Date last modified February 9, 1998