Inherited retinal diseases (IRDs) can cause vision loss that ranges from mild to severe, and can even cause blindness. These diseases affect people of all ages, and different IRDs progress at different rates. They are degenerative and get worse over time. Common IRDs include:
- Leber congenital amaurosis (LCA)
- Retinitis pigmentosa
- Choroideremia
- Stargardt disease
- Achromatopsia
IRDs are caused by a gene that is not functioning properly. Thus far, more than 260 retinal disease genes have been identified. Gene therapy, which corrects and compensates for faulty genes, can help slow disease progression. IRDs are good candidates for this type of therapy due to the location and composition of the retina. Human eyes are small and easily accessible by physicians for treatment.
Eyes are also considered to be “immune privileged,” which means that they have a less active immune response. This immune privilege usually occurs in areas of our bodies that are very important and may be damaged through swelling or inflammation caused by an immune response. Anything implanted into immune-privileged areas, such as the eyes, is less likely to be rejected by the body.
The Gene Therapy Process
The first step toward gene therapy treatment for an IRD is a definitive diagnosis. An IRD can show up at any point in life, so regular ophthalmology testing is important. Once patients are diagnosed, they can sign up for clinical trials for investigational treatments at no cost, depending on their particular genetic mutation.
Most gene therapies use a vector to deliver corrected genetic material to the cell. The most promising vectors are viruses that have had their disease-causing materials removed. Two types of eye injections are used in gene therapy for IRDs:
- Intravitreal injections, which are performed by injecting the therapy directly into the vitreous fluid (the jelly-like fluid contained in the eye).
- Subretinal injections, which are delivered to the subretinal space, allowing the therapy to be closer to the target area of the eye to correct the disease.
Gene therapy is not a cure for IRDs, but it can be successful in slowing or controlling the progression of the disease. Since therapy targets the faulty gene that causes the disease, it eliminates the need for recurring interventions. In sharp contrast to other treatments for retinal disease, in which patients need injections as frequently as once every three months, the goal of gene therapy treatment is to be a one-time administration.
Gene Therapy Pipeline for IRDs
LUXTURNA® was the first FDA-approved gene therapy for an IRD in the U.S., and it has also been approved in the EU. It was developed by the Children’s Hospital of Philadelphia in conjunction with Spark Therapeutics. This gene therapy, which delivers a functional copy of the RPE65 gene into the eye, is suitable for patients who have mutations in both copies of the RPE65 gene.
Other gene therapy approaches for various IRDs are in both preclinical studies and clinical trials, but it is unclear if or when more gene therapy treatments for IRDs will become FDA approved and commercially available. The overall process of FDA approval and arrival on the market can take several years, which helps ensure the therapy’s safety and effectiveness.
QPS has supported cell and gene therapy product development since 2003 on more than 45ASO/siRNA/aptamers and more than 20 mRNA/vectors programs. Our hard-earned experience can help you navigate PK, immunogenicity, biodistribution, viral clearance, and ADME properties of these novel modalities in a rapidly expanding field. We are ready to work with you to determine the specific study parameters and provide complete, fully compliant data packages and reports, ready for submission.
