A luminal vascular coating to reduce time to maturation and failures of AV-Fistulas for hemodialysis access

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 DESCRIPTION (provided by applicant): Research Area: This proposal addresses PHS 2014-02 Omnibus Solicitation of the NIH, CDC, FDA, and ACF for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44]). More than 20 million American adults (1 in 10) have some level of chronic kidney disease (CDC), with a growing incidence in the aging population. Nearly 400,000 ESRD patients receive some form of dialysis, with the vast majority of hemodialysis being performed in a clinic. One of the major causes of morbidity for the ESRD population is hemodialysis vascular access dysfunction, which is responsible for 20% of all hospitalizations for this population. Vascular access accounts for 7.5% of Medicare's spending on the ESRD programs, a total of over $1BB per year. In the past 3 decades, there have been no major advances in the field of hemodialysis vascular access, resulting in a huge unmet clinical need. Native arteriovenous fistula (AVF) is the preferred method of access for hemodialysis because of its low rates of infection and thrombosis once the fistula has fully matured. However, between 23-46% of AVF in Europe and the US have problems with early failure or failure to mature, resulting in a primary patency of only 60-65% at 1 year. Both early and late failures are characterized by vascular stenosis, and the classical histological lesion associated with all AVF failure is neointimal hyperplasia. While many factors play a role in the development of neointimal hyperplasia in an AVF, the extent of damage to the endothelial layer of a vessel has been directly related to the degree of neointimal hyperplasia that occurs. Symic is develop a novel treatment for use in vascular access, aimed at addressing the injury that occurs in the creation of the AV fistula. The localized luminal vascular coating, called DS-SILY, binds to exposed collagen, blocking platelet adhesion to the vessel wall and thus inhibiting the initiating events in thrombosis and neointimal hyperplasia. In the Phase I portion of this work, Symic showed that delivery of DS-SILY to a newly formed fistula significantly increases the diameter of the fistula vein to 3 times the diameter of saline treated controls. Here we will correlate these increased diameters with increased flow rates to confirm that these fistulas are properly maturing for hemodialysis access. Additionally work includes the proper manufacturing controls and safety and toxicology studies necessary to move DS-SILY into early clinical work. Successful completion of this project will lead to the clinical development of a novel therapy to reduce the incidence of failure in vascular access for hemodialysis patients.