AAV Gene Therapy vector CRB1 for retinitis pigmentosa and Leber congenital amaurosis
We developed an adeno-associated viral (AAV) gene therapy vector (AAV-rpqure-1) containing a gene for the treatment of Retinitis Pigmentosa (RP) and Leber congenital amaurosis (LCA) and macular degeneration due to mutations in the CRB1 gene. Preclinical experiments were successful, and we aim for future clinical phase I/IIa experiments. AAV-rpqure-1 was developed by a team of researchers led by Dr Jan Wijnholds at the Leiden University Medical Center (LUMC) and is studied in a clinical pharmaceutical phase pending sufficient finances.
Retinitis pigmentosa (RP) is an inherited disorder that leads to progressive loss of vision initially due to degeneration of rod photoreceptors causing severe night blindness. Subsequent degeneration of cone photoreceptors causes poor or no visual perception. Hereditary RP is caused by mutations in at least one of over 70 genes. Mutations in the CRB1 gene occur in 4% of RP cases and causes blindness in childhood. Night blindness being the most common first symptom in these children. There is no cure for this disease.
Leber Congenital Amaurosis
Leber congenital amaurosis (LCA) is the most severe inherited disorder that leads to early onset loss of visual perception in infants. The first symptoms occur in infants being involuntary movement of the eyes (nystagmus) and increased sensitivity to light (photophobia). LCA is caused by mutations in at least one of over 20 genes. Mutations in the CRB1 gene occur in 10% of LCA cases. Genes that cause LCA are CRB1, RPE65, CEP290, GUCY2D and several less common genes. Clinical gene therapy for RPE65 showed promising results and resulted in a medicine approved for use in the U.S.
Macular Degeneration or Dystrophy in young Adults
Mutations in CRB1 can cause macular degeneration or dystrophy in young adults. There is no cure for this disease.
Retinal Gene Therapy
Retinal gene therapy is the introduction of one or more normal genes into retinal cells (e.g. retinal pigment epithelium, rod and/or cone photoreceptors, Müller glial cells, ganglion cells, bipolar cells, horizontal cells, amacrine cells) in place of missing or corrupted ones in order to correct genetic disorders.