A Cross-over Randomized Control Trial to Evaluate the Retinaldehyde Dehydrogenase Inhibitor, Disulfiram, in Improving Retinal Sensitivity in Eyes Affected by Inherited Retinal Degeneration
Aberrant retinoic acid signaling driven by the degenerating outer retina leads to pathological changes to the inner retina. The resulting hyperactivity of retinal ganglion cells leads to further diminution of the remaining vision in those afflicted with inherited retinal diseases. Inhibition of this pathway has led to improved visual function in murine models of retinal degeneration. This can be accomplished in humans with the FDA-approved irreversible inhibitor of aldehyde dehydrogenases, disulfiram.
⁃ Age ≥18 years Only those with a clinical diagnosis of inherited retinal degeneration. When available, supporting genetic diagnosis form a CLIA approved lab will be further considered for inclusion.
⁃ Only one eye per subject should be identified as the study eye. The study eye must meet the following criteria:
• Best corrected ETDRS visual acuity letter score ≥ 70 (i.e., 20/40 or better) within 30 days of enrollment.
• Goldmann visual field exhibiting constriction of visual fields to 10 degrees centrally
• Able and willing to provide informed consent
• Willing and able to abstain from alcohol consumption for the duration of the study and the 2 weeks preceding it and 2 weeks following the study end point
⁃ Liver function values that fall in the normal range as specified below:
• Alanine transaminase (ALT): less than 40 IU/L
• Aspartate transaminase (AST): less than 40 IU/L
• Alkaline phosphatase (ALP): less than 300 IU/L
• Albumin (Alb): less than 50 g/L
• Total Protein: less than 80 g/L
• Total Bilirubin: less than 30 umol/L