Phase 1 Study of ALK001 for Stargardt Disease

描述（由申请人提供）： 这项研究的总体目标是开发一种口服治疗Stargardt病的方法，Stargardt病是青少年失明的主要原因，在美国的患病率约为万分之一。Stargardt病的视力丧失被认为是源于眼睛中维生素A聚集体（二聚体）和脂褐质颗粒的过度积累。ALK-001是一种维生素A，在特定位置富含氘，以减缓眼睛中有毒维生素A二聚体的形成。在Stargardt病啮齿动物模型中，ALK-001导致维生素A二聚体、眼部脂褐素减少，并改善视觉功能。 ALK-001被认为可以延缓维生素A二聚化和脂褐素形成，而不会影响视觉周期或正常的维生素A加工，因此不会导致视觉或全身副作用。这项工作的主要假设是，延缓维生素A二聚化将减缓脂褐素的形成， Stargardt的路线。 这项资助的目的是进行初步的安全性评估，并确定ALK-001两周给药后的血浆药代动力学，以便设计和进行更长时间的疗效试验。该资助提案的具体目的是完成一项为期2周的每日给药、双盲临床试验，以评估ALK-001在Stargardt病受试者中的安全性和血浆药代动力学。

DESCRIPTION (provided by applicant): The overall goal of this research is to develop an oral treatment for Stargardt disease, a leading cause of juvenile blindness with a prevalence of about 1 in 10,000 in the United States. Vision loss in Stargardt disease is thought to originate from excessive accumulation of vitamin A aggregates (dimers) and lipofuscin granules in the eye. ALK-001, is vitamin A specifically enriched with deuterium at a position to slow the formation of toxic vitamin A dimers in the eye. In rodent models of Stargardt disease ALK-001 resulted in a decrease in vitamin A dimers, ocular lipofuscin and in improved visual function. ALK-001 is thought to retard vitamin A dimerization and lipofuscin formation without affecting the visual cycle or normal vitamin A processing and as a consequence should not lead to visual or systemic side effects. The major hypothesis of this work is that retarding vitamin A dimerization will slow lipofuscin formation and the course of Stargardt. The goal of this grant is to perform preliminary safety evaluation and determine plasma pharmacokinetics in response to two week dosing with ALK-001 so that longer trials for efficacy can be designed and conducted. The specific aim of the grant proposal is to a complete a 2 week daily dosing, double blind, clinical trial to assess the safety and plasma-pharmacokinetics of ALK-001 in subjects with Stargardt disease.