Novel therapy for female sexual dysfunction

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DESCRIPTION (provided by applicant): Female sexual dysfunction is increasingly recognized as a significant and widespread abnormality, contributing to coital pain, decreased libido, and a loss of sexual pleasure. In contrast to the enormous scientific investment in discovering methods to correct male sexual dysfunction, there has been virtually no attention directed at elucidating the fundamental mechanisms accounting for clitoral engorgement, vaginal lubrication, and alterations in vaginal and vulval mucosal blood flows accompanying sexual arousal. We propose to treat female sexual dysfunction with a novel regionally selective nitrovasodilator, L-PEI-NO ("DSI"), expected to serve as a selective vasodilator for the genital circulation when administered topically to the in troitus. In the Phase I SBIR application, we have presented evidence that DS-1 is a promising novel nitric oxide (NO) donor, which has sufficient half-life and bio availability for in vivo studies, and we have proven that DS-1 exerts a powerful and prolonged increase in vaginal mucosal blood flow. Furthermore, the results demonstrated that the effect of the compound is selective, i.e. the local vasodilatation occurs without any systemic hemodynamic effects. We have also made major progress in the chemical synthesis and characterization of the compound. In the current application, we propose to perform additional pre-clinical safety studies with DS1 in order to introduce it into clinical use. We will conduct formal, FDA-mandated synthesis, formulation, ADME, stability, and local irritation and toxicology studies. These studies are expected to provide data demonstrating that repeated chronic administration of DS1 is well tolerated and non-toxic at a dosing regimen 1-2 logs in excess of the predicted therapeutic dose. These data will also establish the target organ for toxicity, which will guide the toxicologic surveillance of future clinical Phase I trials. At the conclusion of the Phase 2 SBIR, Inotek will submit an investigational drug application (IND) to support clinical trials of DS1.