DiaMedica Therapeutics announced the publication of a paper in the peer reviewed journal, Therapeutic Advances in Neurological Disorders, or TAND. The paper summarizes the mechanistic rationale for using KLK1 to treat patients with acute ischemic stroke, or AIS, and summarizes human preclinical and clinical data supporting the hypothesis that KLK1 treatments may improve outcomes after AIS. KLK1, is a serine protease that plays a critical role in the regulation of microcirculation, blood pressure and blood flow. Multiple lines of evidence indicate that KLK1 is important for a healthy cardiovascular system and that deficits in KLK1 are associated with cardiovascular and end-organ pathology. Importantly, KLK1 replenishment therapy is widely used in Asia where multiple forms are used to treat diseases ranging from AIS to complications of diabetes. These diseases involve poor microcirculation or tissue ischemia, which leads to a hypothesis that directly boosting KLK1 levels will improve blood flow and protect tissue under ischemic conditions. The TAND paper reviews the scientific literature covering the biochemical role of KLK1 and presents the mechanistic rationale for using KLK1 as an additional pharmacological treatment for AIS. In addition to the biochemical mechanism of KLK1, the review highlights supporting results from human genetics and preclinical animal models of brain ischemia. It also reviews published clinical results for treatment of AIS by a form of KLK1 that is isolated from human urine. This form has been approved for post-infarct treatment of AIS in the People’s Republic of China and data has been published on clinical trials involving over 4,000 patients. The paper offers a series of testable therapeutic hypotheses for demonstrating the long-term beneficial effect of KLK1 treatment in AIS patients and the reasons for this action.
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