In vivo male fertility is affected by naturally occurring mitochondrial haplotypes

inhibitors has not been possible, perhaps for a combination of reasons, including challenges in function-based screening assays and the intrinsic refractoriness of aquaporins to drug discovery (termed non-druggability). One area of recent progress is in AQP4-based therapeutics for neuromyelitis optica. The idea is to block the binding of pathogenic autoantibodies to astrocyte AQP4, which may provide a targeted, non-immunosuppressive approach to block the diseaseinitiating event in neuromyelitis optica. One approach has been the engineering of a non-pathogenic, tight-binding anti-AQP4 antibody (‘aquaporumab’) that competes with pathogenic autoantibodies; another approach has been the identification, by high-throughput screening, of small-molecule blockers of the autoantibody–AQP4 interaction.