Alpha 1 Antitrypsin Deficiency

Alpha-1 Antitrypsin Deficiency (Alpha 1) is an inherited genetic defect that causes severe loss of lung function and is caused by complete or partial deficiency of the alpha-1 antitrypsin protein. Alpha-1 is one of the most common serious hereditary disorders in the world, with an estimated patient population of 200,000 in the US and Europe, and can result in life-threatening liver disease in children and adults or in lung disease in adults.
Alpha-1 augmentation therapy (treatment with weekly infusions of alpha-1 antitrypsin protein, purified from plasma obtained from human donors) has been available since 1987. There are three main drawbacks to this augmentation therapy: the requirement for IV infusion every one to two weeks, the high cost, typically $100,000 per year, and the limited supply causing rationing. Supplies remain low because of the limited number of human plasma donors.

AGTC is developing a gene therapy product to treat Alpha-1. In a Phase 1 clinical trial with this product, the only treatment-related adverse events were mild and short-lived reactions at the injection site, and the group receiving the highest dose tested had expression of alpha-1 antitrypsin protein in serum that was sustained for at least 1 year. A Phase 2 clinical trial testing even higher doses of the product is ongoing.
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Leber Congenital Amaurosis

Leber congenital amaurosis (LCA) is a rare inherited retinal degenerative disease characterized by severe loss of vision early in life. There are more than a dozen known genes that can cause LCA. There is no treatment available for LCA.
Under sponsorship from the National Eye Institute, pre-clinical studies of a gene therapy product for one genetic form of LCA, caused by mutations in the RPE65 gene, have been performed in collaboration between The University of Florida, The University of Pennsylvania, and Cornell University. Results from several Phase 1 clinical trials have reported an acceptable safety profile and improvement in visual function in most patients. A Phase 1/2 clinical trial sponsored by AGTC is ongoing.
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Visit patient sites:
Foundation Fighting Blindness
The Foundation for Retinal Research

Wet Age-Related Macular Degeneration

Wet AMD is the leading cause of blindness in the US, with more than 1.6 million people affected. Each year approximately 200,000 new cases are diagnosed in the US and more than 500,000 worldwide.

The macula is the area of the retina essential for fine-detail vision required for activities such as reading and driving. In patients with wet AMD, the macula is disrupted by fluid leaking from new blood vessels that have grown under the retina. This leads to loss of central vision which effectively blinds a patient for most normal activities.

A key signal of new vessel growth (neovascularization) is vascular endothelial growth factor (VEGF). VEGF also promotes leakiness of the new vessels. These twin effects have made VEGF a key target of AMD drug development efforts. Two recently developed compounds, pegabtanib (Macugen) and ranibizumab (Lucentis), which target VEGF and reduce neovascularization, have been approved by the FDA for treatment of wet AMD. Effective treatment with each of these drugs requires frequent injections into the affected eye. This is not only inconvenient but is a significant hurdle for many patients.

AGTC, in collaboration with Genzyme Corp., is developing a gene therapy product that will provide long-term suppression of VEGF. The product will remain resident in the treated eye and the patients' own cells will produce the VEGF blocking agent continuously and exactly where it is needed. If proven to be effective, this will free patients and physicians from the need for frequent injections. A Phase 1 clinical trial of this product is ongoing.
For Additional Details

Visit patient sites:
Foundation Fighting Blindness
The Macula Vision Research Foundation
Research to Prevent Blindness