Topical Treatment - Raynaud’s

About

Invention Description and Novelty:  Systemic sclerosis (also known as scleroderma, SSc) is an autoimmune connective tissue disease that is characterized by the presence of Raynaud’s phenomenon (RP) that manifests by repeated episodes of vasospasm of the distal arteries upon cold exposure leading to reduced tissue perfusion and hypoxia. It is estimated that over 95% of patients with SSc suffer from RP. Current treatments of RP are not satisfactory in general, as therapies employing calcium channel blockers and other vasodilator agents are either not effective or not well tolerated, due to significant side effects. This invention describes a transient receptor potential meastatin-8 (TRPM-8) antagonist composition that blocks TRPM8 activation in skin cells. Applications: Novel topical treatment for Raynaud’s phenomenon and/or pain to fingers, hands, toes, or feet from exposure to cold. Value propositions: Topical formulation is suitable for use in treating RP, pain from exposure to cold, or cold-induced vascular dysfunction over a period of about two to six hours. Composition and method inhibits transient receptor potential meastatin-8 (TRPM-8) in SSc microvascular endothelial cells (MVEC) and vascular smooth muscle cells (VSMC). Composition reduces the expression of endotheline-1 (ET1), and increases endothelial nitric oxide synthase (NOS3) and prostacyclin synthase (PTGIS) mRNA expression in skin cells, which relieves cold-induced vascular spasms. Thermal images correlate with dynamic changes in blood flow in the digital arteries. Local application of the composition prevented the cold induced decrease in blood flow to the fingers after topical application, associated with subjective feeling of less finger coldness by patient report. Compared with oral delivery, topical administration leads to high dermal concentration of drugs with minimal or no side effects.