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Baby Blindness Gene Discovered
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by ScienceDave | June 3, 2007 at 09:49 pm
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Leber Congenital Amaurosis (LCA), the most common form of blindness in infants and children affects approximately 1 out of 35 000 births [source], accounting for 5% of all hereditary retinal degenerations [source]. According to The Foundation for Retinal Research, "Of all the retinal degenerations, LCA has the earliest age of onset and can be the most severe." [source]
An international team of geneticists, led by Dr. Robert Koenekoop from the McGill University Health Centre, discovered a novel gene that causes LCA (called LCA5). Interestingly, LCA5, one of nine other genes to cause LCA, was found by using one of the other nine genes (CEP260). By probing the genomes of an affected individual using a modified form of CEP260, the investigators discovered LCA5 (like using a slightly modified square peg to find a different square hole, who's fit is dictated by their resemblance to each other).
CEP260 was discovered by Koenekoop and other researchers last October, and was hailed as, "...the single most important gene for congenital blindness just based on numbers, frequency and impact," said Koenekoop" [source]. Along with LCA5, these two genes account for 25-30% of all LCA cases.
What is LCA?
Characteristics of LCA can be broken down into two categories (following TFRR):
1) Physical - the most common are vision loss, roving eyes, sluggish pupillary response, and sometimes eye-rubbing. The less common characteristics include cataracts, aversion to light,
2) Genetic - according to TFRR, there are currently nine different genetic mutations that can lead to LCA. LCA is a subgroup of other hereditary diseases, termed Retinitis Pigmentosa, characterized by the degeneration of the retina.
What Causes LCA?
To understand the causes of LCA, one must first understand how the eye works. Most are familiar with how a camera functions, and our eye is very similar. Light passes first through the cornea, the hard protective coating of iris, where it then enters the iris. The iris can be adjusted to allow more or less light into the lens, which ultimately focuses light onto your retina (the equivalent of film in a camera). Any defects of these components, or subcomponents responsible for manipulating them, can result in vision impairment (like near- or farsightedness, where the lens is unable to focus light reflected from objects afar or nearby, respectively).
Ok, so what component of the eye is affected by LCA? According to FFB, the photoreceptor cells on the retina (cone cells for colour, rod cells for black and white), the cells responsible for converting light into chemical signals for the brain to interpret (the equivalent to the chemicals lain into unexposed film), either develop abnormally or degenerate prematurely. For example, if you buy film off the bargain rack at a camera shop that expired 10 years ago, the chemicals in the film that will capture your sunset will not work as they would have 10 years ago. The "film" in individuals with LCA, however, was either botched in the film factory, or will expire faster than normal "film".
Current LCA Treatment Options
Currently, there are five potential treatments in practice for LCA, three of which are currently in clinical trials (1-2,5) and two that are theoretical (3-4):
1) Gene Therapy
One of the best possibilities of a treatment and perhaps even a cure for LCA could come from Gene Therapy – more correctly, Gene Replacement Therapy. Simply, if there is a mutated gene that produces a malfunctioning protein or no protein at all, replacement with a normal gene in the proper cell type should result in synthesis of a normal protein, hopefully at a proper level with subsequent restoration of visual function. As outlined above though, Gene Therapy can only be successful if target cells (e.g., photoreceptor cells) are alive.
Gene therapy in dogs shows promise...
"We have shown that gene therapy can restore vision in dogs with one of the most clinically severe retinal degenerations," said Acland, a research veterinarian at Cornell's James A. Baker Institute for Animal Health. "Many safety and efficacy studies must be performed before we can begin clinical trials, but this [gene therapy] could correct defects in humans with RPE65 mutations," Acland said.
2) Drug Therapy
Over the last few years, agents, drugs, natural growth factors, etc. have been identified that protect neuronal tissue against insult...One of the most successful is Ciliary Neurotrophic Factor (CNTF)...CNTF, is currently in clinical trial for forms of Retinitis Pigmentosa. The Phase 1 Study (safety) has been successfully completed and the Phase 2 Study (efficacy) is soon to commence. If successful, it should afford the first treatment for a rare human retinal degenerative disease and be available for general patient application in a few years.
3) Cell Transplantation and 4) Stem Cells - although human trials are not underway, both of these could potentially restore sight in the affected patients.
5) Electronic Prosthetic Devices
In a retinal degeneration, the prosthetic device would essentially take the place of the lost photoreceptor cells. Functionally, the photoreceptor cell captures the photic (light) energy and converts this energy to a chemical and then electrical signal and transmits this signal to secondary retinal neurons for processing and transmission to the brain....several prosthetic device projects are underway across the world
Future of LCA Treatments
“Discoveries like this one show us that treatments and cures are in sight. The Foundation Fighting Blindness in Canada is proud to fund quality vision research at the MUCH that is giving hope to families affected by blindness,” says Sharon Colle, National Executive Director of the FFB-C
Clinical trials have very recently been approved both in the United States and Britain to begin testing the safety and efficacy of gene therapy for the treatment of LCA. In this case the gene of interest is RPE65, and is responsible for approximately 5% of LCA cases.
Furthermore, clinical trials have been long underway for the Electronic Prosthetic devices...
The researchers from Optobionics in Wheaton, IL, have already implanted up to ten artificial retinas as a part of their FDA approved, two-year safety study.
So far, there have been no serious complications and no signs of degradation or rejection. The durability of the microchip and the long-term safety of the procedure have yet to be determined by the study.
LINKS
The Foundation for Retinal Research
The Foundation Fighting Blindness
British Clinical Trials
US Clinical Trials
Gene Therapy in Dogs
Artificial Silicon Retina (ASR)
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Most RecentMost Recommended Comments (1)
at 23:00 on June 3rd, 2007
Very well informative article. Its always great to hear of medical breakouts... Good stuff.