ASURAGEN, INC. — Department of Health and Human Services SBIR Phase II: DESCRIPTION (provided by applicant): The long term goal of this project is to develop accu

Description

DESCRIPTION (provided by applicant): The long term goal of this project is to develop accurate, rapid, high throughput and cost-effective screening for fragile X syndrome (FXS) and related disorders. FXS is the most common known genetic cause of autism andinherited intellectual disability, and affects roughly 1 in 4,000 males and 1 in 6,000 females. The incidence of fragile X carriers is as high as 1 in 130 in females and 1 in 250 in males, and these individuals are at risk for additional disorders that impact childhood early development, including autism. Newborn screening (NBS) for fragile X is timely due to the disease prevalence, lack of a clear phenotype at birth and corresponding diagnostic odyssey , current and emerging options for early interventions, and impact of associated syndromes. Access to an inexpensive and effective high throughput screening technology, however, has been a key hurdle. To address this technology gap, Asuragen has demonstrated feasibility in phase I studies for a streamlinedand automated system for blood card processing and fragile X gene detection that exploits an optimized PCR reagent set. Phase I studies were highly successful, resulting in a technology that can consistently and accurately detect fragile X expansions. InPhase II commercialization, these capabilities will be extended by automating a novel, multiplexed screening assay, developing and integrating an innovative set of controls that ensure reliable data interpretations, establishing an automated algorithm foridentifying positives using a workflow that can accommodate thousands of samples per day, and incorporating a confirmation approach that leverages Asuragen's validated AmplideX product technology. As a result, Asuragen will expand on previously successful fragile X SBIR proposals that have led to multiple cutting-edge products by leveraging a team and environment that is ideally suited to develop, optimize, manufacture, and commercialize the proposed Phase II product. The specific aims of this proposal are: Aim 1: Develop and integrate a set of controls, standards, reagents and QC metrics in an optimized workflow that enables high throughput fragile X NBS from FMR1 normal and mutant blood spots. Aim 2: Establish a screening system that integrates automated assay methods and software that can enable the automated analysis of up to 4000 blood spot samples per day. Aim 3: Validate the system in a retrospective clinical study that includes at least 10,000 newborn blood spot samples, with confirmatory reflextesting of expanded alleles. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: We are developing an automated, rapid, accurate and cost-effective molecular test for screening newborns to detect the characteristic genetic mutation associated with Fragile X Syndrome. Fragile X is one of the most commonly inherited forms of mental retardation and can also cause conditions such as ADHD and autism. The diagnostic tests detects DNA from a small drop of blood spotted on paper and will support early diagnosis which may be beneficial because of current and emerging options for early interventions.