Our Focus

Restoring the Body's Supply of an Essential Protein

DiaMedica Therapeutics is developing DM199, a recombinant protein replacement therapy intended to restore normal, healthy levels of a protein known as tissue kallikrein 1 (KLK1). KLK1 is a naturally-occurring protein believed to stimulate the production of nitric oxide, cGMP, prostaglandin and cAMP—factors that improve blood flow and reduce inflammation. DM199 has the potential to treat several acute and chronic diseases.

Replenishing KLK1 Levels

DM199 therapy is intended to restore normal levels of the protein known as tissue kallikrein 1 (KLK1) in patients. The restoration of this protein is intended to allow patients to naturally regulate their blood flow and maintain vascular homeostasis as well as reduce inflammation and oxidative stress.

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KLK1 Replenishes Key Signaling Molecules

KLK1 is a serine protease (enzyme) primarily produced in the kidneys, as well as in the pancreas and salivary glands. KLK1 is believed to be responsible for producing nitric oxide and prostaglandins, so-called "signaling molecules," that work together to play a critical role in regulating many body systems. Nobel Prizes in Physiology and Medicine were awarded in 1982 and 1998 to scientists that researched the importance of these signaling molecules. KLK1 is the key protein in the kallikrein-kinin system, which promotes local blood flow and vasodilation and mitigates inflammation and oxidative stress by selectively delivering these signaling molecules when and where they are needed.

DM199 and KLK1

DM199 is a recombinant (synthetic) form of human KLK1. We developed DM199 to combat a variety of diseases associated with reduced or low levels of KLK1. Our initial focus is on treating acute ischemic stroke (AIS) and chronic kidney disease (CKD), however, DM199 may be a potential treatment for other vascular conditions as well.

The Synergistic Effects of KLK1 Replacement

DM199 is a synthetic form of KLK1, which can be administered intravenously or subcutaneously to potentially restore KLK1 to normal, healthy levels. KLK1 activates bradykinin receptors, primarily the bradykinin 2 receptor, that stimulate the production of nitric oxide, prostaglandins and anti-inflammatory mediators that, working together, may ultimately improve stroke outcomes and restore kidney function.

DM199's Effect on Kidney Function

KLK1 is believed to promote the dilatation of both the afferent and efferent arterioles in the kidney, improving micro vascularization and blood flow while reducing intra-kidney pressure. In addition, KLK1 is thought to improve the kidney's ability to filter blood (glomerular function) by reducing inflammation, oxidative stress and fibrosis. It is further hypothesized that KLK1 plays a role in regulating epithelial sodium channels (ENaC), which regulates the body’s retention or elimination of sodium, and in increasing the production of regulatory T cells which may help to halt autoimmune attacks.

Novel Approaches to Acute and Chronic Diseases

At DiaMedica, we are developing DM199 as a novel and promising new therapy to restore normal levels of KLK1 and healthy function of the kallikrein-kinin system to address multiple serious diseases characterized by KLK1 deficiencies.