In the 62 million companion dog population in the United States, there has been a three-fold increase in diabetes mellitus (DM) over the last 30 years. In dogs, DM is characterized by the rapid onset of bilateral sugar cataracts which often result in vision loss. Today, nearly one in three 3 dogs with cataracts is diabetic. Sugar cataracts cannot be currently prevented and surgery is the only treatment available. The $2,500 - $5,000 cost for this surgery, however, can be prohibitive because it is not covered by most insurance policies. To address the significant need for an alternate treatment for sugar cataracts, this proposal seeks to develop a topical aldose reductase inhibitor (ARI) formulation, Kinostat, for the veterinary market. Studies have established that aldose reductase initiates sugar cataracts in both diabetic and galactosemic animals and that ARIs prevent sugar cataract formation in both of these animal models. Based on prevention studies in dogs that report that oral administration of ARIs reduce sugar cataract formation in a dose-dependent manner, we have demonstrated in preliminary results that topical Kinostat treatment of galactose-fed beagles with cortical sugar cataracts not only arrests cataract development, but actually partially reverses early sugar cataracts. This indicates that Kinostat not only may serve as a prophylactic treatment against the formation of cataracts but that it can restore functional vision in the dogs with early sugar cataracts, thus reducing the need for surgery in the growing population dogs with DM . Based on these results, the specific aim of Phase I of this proposal is to conduct a 12-month pilot clinical trial with 30 """"""""volunteer"""""""" dogs of various breeds with DM to demonstrate that topical Kinostat can inhibit sugar cataract formation and as a result maintain functional vision in diabetic dogs. Lens changes will be documented by retroillumination photography and the extent of opacification in these images will be quantified by computer image analysis. The successful demonstration of Kinostat efficacy in Phase I of this study will be followed in Phase II by a multi-center, masked clinical trial in which Kinostat or placebo will be administered to diabetic dogs with little or no lens changes and no overt cortical or nuclear opacities. Following the demonstration of efficacy in Phase II for successfully inhibiting or significantly delaying the onset and progression of sugar cataracts, Kinostat will be marketed for veterinary use. The availability of a topical inhibitor of sugar cataracts could benefit an estimated 400,000 companion dogs in the United States by reducing the need for cataract surgery. This proposal seeks to develop a topical drug, Kinostat, for the prevention/treatment of sugar cataracts in dogs with diabetes mellitus (DM). Based on preliminary results where Kinostat not only served as a prophylactic treatment against the formation of sugar cataracts but also restored functional vision in galactose-fed dogs with early sugar cataracts, the specific aim of this proposal is to conduct a 12-month pilot trial with 30 """"""""volunteer"""""""" dogs of various breeds with DM. The successful demonstration in this Phase I study that topical Kinostat inhibits sugar cataract formation and maintains functional vision in dogs with DM so that the need for cataract surgery is reduced, will be followed in Phase II by a multi-center, masked clinical trial with our ultimate goal being the marketing of Kinostat for veterinary use so that the need for surgery is aleviated in an estimated 400,000 diabetic companion dogs that develop DM in the United States. ? ? ?
|Kador, Peter F; Wyman, Milton; Oates, Peter J (2016) Aldose reductase, ocular diabetic complications and the development of topical Kinostat(®). Prog Retin Eye Res 54:1-29|
|Kador, Peter F; Webb, Terah R; Bras, Dineli et al. (2010) Topical KINOSTAT™ ameliorates the clinical development and progression of cataracts in dogs with diabetes mellitus. Vet Ophthalmol 13:363-8|