Total rod ERG suppression with high dose compassionate Fenretinide usage

Abstract

Fenretinide is a synthetic retinoid that interferes with the attachment of retinol to retinol binding protein. It may inhibit accumulation of A2E and lipofuscin, and is proposed as therapy for Stargardt disease. It is currently used for cancer therapy, and mild depression of rod function and dark adaptation is a side effect at standard dosage. We studied two youngsters (aged between 12 and 13) receiving high doses as compassionate treatment for neuroblastoma: 800 mg daily for 1 out of every 3 weeks, for roughly 2 years. Goldmann-Weekers dark adaptometry, ISCEV standard ERG and mfERG were performed, and blood was analyzed for vitamin A. Neither child complained of night blindness or showed retinal fundus abnormalities. On initial exam, dark adaptation thresholds were elevated by 3 log units, and there were no detectable rod ERG responses. However, cone responses and mfERG were normal. Retesting one subject 3 months after stopping the drug revealed normal rod thresholds (slightly delayed) and low normal rod ERG responses. Serum vitamin A levels were normal from both subjects, but there is no record of whether the samples were drawn during cycles on or off drug. Our study demonstrates that high dose Fenretinide can suppress rod function quite completely, although serum vitamin A and rod function apparently return to normal or near normal levels rapidly once the drug is stopped. It is intriguing that cone function and access to vitamin A seems largely independent of Fenretinide effects on retinol availability.

Safety and Effect on Rod Function of Acu-4429, a Novel Small-Molecule Visual Cycle Modulator

“…This suppression is similar to that seen with fenretinide. 18,19 These findings document the potential of ACU-4429 to reduce the accumulation of A2E in pathologic conditions such as dry AMD.…”

Rescue of the Stargardt phenotype in Abca4 knockout mice through inhibition of vitamin A dimerization

“…These include inhibiting retinal pigment epithelium-specific 65-kDa protein (RPE65), retinol-binding-protein (RBP), or introducing molecules, such as foreign amines, into the eye to react with retinaldehyde. A necessary consequence of depriving the photoreceptors of vitamin A is rod-mediated or peripheral visual dysfunction (38,39). However, patients with ABCA4-related retinopathies first lose central vision and rely on peripheral vision.…”

Chemoprevention of Head and Neck Cancers: Does It Have Only One Face?

“…Marmor points out that large doses of fenretinide may completely block the rod cell functions, yet that is reversible after discontinuation of treatment. Fenretinide seems not to influence the functioning of cone cells [ 114 ]. Most of the side effects of treatment are reversible, yet in some 4.4% of patients those symptoms are maintained after discontinuation of treatment [ 115 ].…”