Seminar: Dr. Robert Koenekoop

From Retinal Gene Discovery of NMNAT1 to Therapies for Blindness: Do Therapies Improve Visual Function, Retard Disease Progression or Both?

Date:
17 April 2013 00:00 hrs.
Location:
Location see remarks
Title:
From Retinal Gene Discovery of NMNAT1 to Therapies for Blindness: Do Therapies Improve Visual Function, Retard Disease Progression or Both?
Speaker(s):

Robert K. Koenekoop, MD, PhD, McGill Ocular Genetics Laboratory, Montreal, Canada

Host(s):

Prof. F.P.M. Cremers, Department of Human Genetics, RUNMC

17-04-2013 00:00:00Europe/AmsterdamFrom Retinal Gene Discovery of NMNAT1 to Therapies for Blindness: Do Therapies Improve Visual Function, Retard Disease Progression or Both? Location see remarksRimlsrimls@radboudumc.nl

Remarks / more information:

Koenekoop, RobertExome sequencing of a large cohort of patients with congenital blindness (LCA) yielded DNA sequence variants in NMNAT1, located in the LCA9 locus. Persons with NMNAT1variants show conspicuous macular coloboma's. NMNAT1encodes the nuclear isoform of nicotinamide mononucleotide adenyltransferase, a rate-limiting enzyme in NAD+ biosynthesis. Nmnat1 is the principal component of the mouse Wallerian degeneration fusion protein (Wlds), which also includes a 70-residue N-terminal sequence from the Ube4b multiubiquitination factor, and has been shown to have neuroprotective activity.

LCA patients withRPE65andLRATvariants are unable to recycle retinoids and do not have 11-cisretinal, the crucial ligand of opsins. QLT091001, a synthetic retinoid, restored visual function in mouse and dog models withRPE65orLRATdefects and was safe in human volunteers. Fourteen persons obtained QLT091001 orally for 7 days and were followed up to 24 months. Significant improvements were found in visual acuity, color vision and Goldmann visual fields. Improvements in activities of daily living were reported without serious adverse events.



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