MeiraGTx (Nasdaq: MGTX), has announced two pre-clinical programs addressing Inherited Retinal Diseases (IRDs) caused by mutations in KCNV2 and GUCY2D, for cone-dystrophy, and are presented with data supporting the development of their AAV viral vectors and CRISPR technologies. MGTX now reports six programs in clinical development in both preclinical and clinical research studies. The company is aiming to license, acquire, and develop multiple technologies in the gene therapy space for ocular, inherited retinal diseases and other large degenerative diseases.
The company specifically reported that a recent KCNV2 retinal organoid disease model project aims to use AAV-KCNV2-mediated gene therapy for the treatment of patients with cone-dystrophy. The KCNV2 project uses CRISPR/Cas9 gene editing to generate human KCNV2 knockouts and isogenic human control retinal organoids. KCNV2 knockout retinal organoids are to be used to screen eight AAV vectors containing expression cassettes coding for either WT (wild type) or codon-optimized versions of hKCNV2, as driven by either constitutive (CAG) or photoreceptor-specific rhodopsin kinase (RK) promoters. Both AAV5 and AAV7m8 vectors are to be assessed for their ability to restore hKCNV2 RNA expression and Kv8.2 localization to the inner segment of rod and cone photoreceptor cells following transduction.
In a separate study, a GUCY2D retinal organoid disease model uses an AAV gene therapy development program, ultimately for applying novel technologies for patients with cone-rod dystrophy. According to the researchers, four AAV vectors are to be packaged into 7m8 capsids designed to enable the restoration of GUCY2D-mediated signaling in photoreceptor outer segments via gene replacement. Transduction of GUCY2D knockout (GUCY2D KO) human retinal organoids by all vectors is proposed to improve quantitative expression levels of GUCY2D and PDE6β relative to non-transduced controls, and total cGMP levels in transduced GUCY2D knockout human retinal organoids may demonstrate vector potency and transgene function. The company’s results suggest that gene replacement in GUCY2D-deficient human retinal organoids may restore protein expression and cGMP levels in transduced organoids as an ultimate treatment for patients caused by mutations in GUCY2D. According to MeiraGTx, Alexandria Forbes, Ph.D., President and Chief Executive Officer have commented that,“we’re pleased to present data illustrating the depth and versatility of our scientific platform, [to] developing novel vectors for gene replacement therapies in inherited diseases such as IRDs, we have aimed to develop gene regulation technology that may be applied to larger more common diseases”.