This therapy delivers a working copy of a faulty gene to the appropriate cell. It may also deliver a gene that produces a therapeutic substance.
All living organisms have DNA. Various non-lethal types of viruses have been found to be successful delivery mechanisms. The virus’s own DNA is removed and a working copy of the gene is inserted into this viral vector. The virus is then replicated thousands of times and then introduced into retina. The retinal cells pick up on this new genetic information and the correct protein is then produced in the cell.
Gene therapy to treat various forms of IRD at present in clinical trials:
- RPE65 gene for Leber Congenital Amaurosis [LCA]
- Stargen for ABCA4 Stargardt Disease and Cone Rod Dystrophy
- UshSTAT for Usher Syndrome Type 1b [ MYO7A gene ]
- Nightstar for Choroideremia
- X Linked Retinitis Pigmentosa [RP]
- AIPL1 gene for LCA
These are compounds or interventions that show protection for photoreceptors and slow the rate of degeneration:
- Growth factors- a clinical trial by Neurotech is in process
- Rod-derived Cone Viability Factor (RdCVF)- This is a potent promoter of cone cell viability- a clinical trial is being planned.
- Transcorneal Electrical Stimulation (TES) – has shown modest improvement possibly by increasing neurotrophic agents
The AREDS formula for Dry AMD slows the conversion to wet AMD
Retina Plus [Complex] showed retinal preservation in mouse models. The patient study in Spain was not completed.
Over 30 natural and man-made factors are being studied that act as neuron-survival agents.
Anti – VEGF injections for wet AMD are often very successful. They are now also being used to treat diabetic retinopathy and diabetic macular oedema.
QLT Retinoid for specific genetic types of LCA and RP
Drugs used in other conditions eg. glaucoma, epilepsy and statins are being studied.
Nano particle delivery of small molecules offer a possible solution to deliver therapeutic substances over the blood / retina barrier.
These are devices with a silicon chip and electronic circuitry to replace the dying photoreceptor cells.
They all require an intact neural pathway to transfer messages to the visual cortex in the brain.
There are sub-retinal, epi-retinal and suprachoriodal types.
Many are in clinical trials or have been approved for commercial use. The most popular are:
Thera are also many others from Israel, Australia, etc.
Stem cells are pluripotent cells that occur in early stages of embryonic development – super cells that can become any cell in the body.
After 14 days they start to specialise to become one of 350 cell types that make up the human body.
These specialised cells are still present in the adult mammal and are found in various cells including bone marrow, the blood, the brain and even the eye.
Researchers are using stem cells from all these sources, manipulating them to become retinal cells and then introducing them into the retina. They are using cells derived from:
- Embryonic stem cells, human central nervous system stem cells, umbilical cord stems cells and even induced pluripotent cells derived from adult cells, skin cells, bone marrow, etc.
Some interventions are showing tremendous promise:
- Embryonic stem cells to grow new retinal pigment epithelial cells for AMD and Stargardt Disease.
- Embryonic stem cells to grow progenitor photoreceptors for RP.
Even with advanced photoreceptor cell death, the retinal neural layer remains quite intact. These cells are an integral pathway to vision, but are not light sensitive. Researchers are conferring light sensitivity by the transfer of molecules or genes that produce light sensitive molecules to these cells.
Early tests in canine and primate models are showing great promise.
Phase 1 Clinical trials have begun and three patients have been treated.
There are thousands of clinical trials in progress, for more information about clinical trials for a specific IRD see www.clinicaltrials.gov
Photo from left: Lisa Roberts, Prof Jacquie Greenberg and Prof Raj Ramesar
Retina South Africa has been in partnership with the Division of Human Genetics at the University of Cape Town headed by Professor Raj Ramesar since 1991.
The focus of the main project is to find the precise genetic mistake in every South African family.
Other projects include:
- The genetics of RD in Black indigenous SA families
- Identifying the molecular pathogenesis in individuals with the spliceosomal factor PRPf8
- Exome sequencing in South Africa and feedback of individual research results to families
- Investigation of Genetic Modifiers that results in different phenotypes in heterozygous females with XLRP2 mutations
- Rod Cone Dystrophy with sensorineural deafness and renal dysfunction
- Identification of the genetic defect in recessive RP family of Asian origin
- Exploration of the impact of genetic counselling and patient support group involvement on RDD patients
- Young adults’ perceptions of the implications of their hereditary visual impairment.
Retina South Africa facilitates genetic testing of individuals earmarked for research projects and for patients who wish to pursue genetic testing privately. For more information contact the national office.