Development of Kv1.3 channel blocker ShK-186 as a therapy for multiple sclerosis
Small Business Information
KINETA, INC., 307 WESTLAKE AVE N, STE 200, SEATTLE, WA, -
AbstractDESCRIPTION (provided by applicant): Multiple sclerosis (MS) affects approximately 400,000 Americans and constitutes a progressive, disabling disease for which current therapies are inadequate. This application describes the nonclinical development of ShK- 186, a novel Kv1.3 potassium channel inhibitor that targets the effector memory T cell (TEM) population in MS. TEM cells play a prominent role in the tissue damage associated with autoimmune disease, and autoreactive Kv1.3-dependent TEM cells have been ide ntified in the CNS, synovial fluid, and peripheral blood of MS, rheumatoid arthritis, and type 1 diabetes mellitus patients. ShK-186 was discovered by Dr. George Chandy (co-PI) and his group at the University of California at Irvine. The drug is being deve loped commercially by KINETA Inc. of Seattle, WA. ShK-186 inhibits Kv1.3 potassium channel function with picomolar potency and reduces mitogen-stimulated cytokine production, [3H]-thymidine incorporation, cell motility, and antigen-presenting cell interact ion by TEM cells. In addition, ShK-186 and its closely-related analog, ShK-170 have been shown to prevent and treat disease in a number of autoimmune animal models including adoptive-transfer experimental autoimmune encephalitis (EAE), immunization-mediate d, chronic relapsing EAE (CR-EAE), and pristane-induced arthritis. ShK-186 has demonstrated excellent tolerability and safety in preclinical animal models including in a 28-day, repeat dose toxicity study in rat. The drug demonstrates excellent specificity for Kv1.3 in receptor profiling studies, and there is no evidence for cardiac toxicity including in ECG telemetry studies of conscious rats. The present application will undertake: (1) further preclinical studies in the CR-EAE model to better define the r elationship between dose, dose frequency, and treatment period on drug efficacy, (2) GLP tolerability and toxicology studies in rat to support an Investigational New Drug application for ShK-186 to the Food and Drug Administration, and (3) preparation of t he pre-IND and IND submission documents. The major milestone of this two-year program is the submission to FDA of an IND application intended to support first-in-human clinical trials of ShK-186. PUBLIC HEALTH RELEVANCE: This project involves the devel opment of a drug, ShK-186, to treat multiple sclerosis and other autoimmune diseases. The drug targets a specific population of immune cells termed effector memory T cells .
* information listed above is at the time of submission.