AI Article Synopsis
- The study tested the effects of hypocretin-1 on narcolepsy in dogs, focusing on two models with different genetics.
- Despite the drug inducing wakefulness in control dogs when administered directly into the brain, it did not impact cataplexy or wakefulness in Dobermans with a specific gene mutation.
- The findings suggest that systemic delivery of hypocretin-1 is ineffective as it struggles to cross the blood-brain barrier, indicating a need for improved versions of the drug.
Article Abstract
Study Objectives: Using two different canine models of narcolepsy, we evaluated the therapeutic effects of hypocretin-1 on cataplexy and sleep.
Measurements And Results: Intracerebroventricular administration of hypocretin-1 (10 and 30 nmol per dog) but not intravenous administration (up to 6 microg/kg) induced significant wakefulness in control dogs. However, hypocretin-1 had no effect on cataplexy or wakefulness in hypocretin receptor-2 gene (Hcrtr2) mutated narcoleptic Dobermans. Only very high intravenously doses of hypocretin-1 (96-384 microg/kg) penetrated the brain, to produce a short-lasting anticataplectic effect in a hypocretin-ligand-deficient animal.
Conclusions: Hypocretin-1 administration, by central and systemic routes, does not improve narcoleptic symptoms in Hcrtr2 mutated Dobermans. Systemic hypocretin-1 hardly crosses the blood-brain barrier to produce therapeutic effects. The development of more centrally penetrable and longer lasting hypocretin analogs will be needed to further explore this therapeutic pathway in humans.
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| http://dx.doi.org/10.1093/sleep/26.8.953 | DOI Listing |
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