US researchers investigate gene therapy treatment for X-linked retinitis pigmentosa

2 May 2016 (Last Updated May 2nd, 2016 18:30)

Researchers from the University of Pennsylvania have revealed a new animal study data, which analyses the efficacy of an investigational, adeno-associated virus (AAV) vector gene therapy treatment for X-linked retinitis pigmentosa (XLRP).

Researchers from the US University of Pennsylvania have revealed a new animal study data, which analyses the efficacy of an investigational, adeno-associated virus (AAV) vector gene therapy treatment for X-linked retinitis pigmentosa (XLRP).

XLRP is a rare inherited retinal disease that results in progressive vision loss in boys and young men.

The disease begins with night blindness in young boys, followed by progressive constriction of the field of vision. Affected men go blind at an average age of 45 years.

The investigational gene therapy has been developed by Applied Genetic Technologies Corporation, a biotechnology company that carries out human clinical trials of gene therapies for the treatment of rare diseases.

"These study results demonstrate that a human optimised version of this novel AAV-based gene therapy approach could have clinical potential in treating XLRP."

A study was conducted at the Universities of Pennsylvania and Florida, comparing the short-term efficacy of two different AAV2/5 constructs carrying either a codon-optimised RPGR cDNA (RPGR1), or a previously evaluated RPGR cDNA (RPGR2) in the functional rescue of photoreceptors in a canine model of XLRP.

The investigation included seven dogs who were affected with XLRP and treated with a subretinal injection of either AAV2/5-GRK1-RPGR1 (five eyes) or AAV2/5-GRK1-RPGR2 (four eyes).

The dogs were carefully observed 12 or 18 weeks after they were given the injection.

Rescue of photoreceptor structure and function was evaluated by electroretinography (ERG), retinal imaging and histology / immunohistochemistry (IHC) at termination.

The investigation revealed that rod-mediated ERG function was improved in four out of five RPGR1-treated eyes and all three RPGR2-treated eyes, compared to untreated eyes.

The treated eyes revealed a significant preservation of the thickness of their outer nuclear layer.

IHC testing reported that RPGR transgene expression was visible significantly in rods, but associated with improved structure of both rods and cones, and correction of rod and cone opsin mislocation.

University of Pennsylvania School of Veterinary Medicine Ophthalmology associate professor and lead study investigator William Beltran said: "These study results demonstrate that a human optimised version of this novel AAV-based gene therapy approach could have clinical potential in treating XLRP, a severe inherited retinal disease without adequate treatment options.

"We have made significant progress in advancing the field of ocular gene therapy and these data confirming efficacy in a large animal model suggest a future path for human clinical studies."

It was concluded that improvement of both rods and cones was achieved after treatment with both vectors, with no specific efficacy differences observed.