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 human tissue kallikrein-1 (KLK1). KLK1 is a naturally-occurring protein believed to stimulate the production of nitric oxide and prostaglandin - critical local hormones that are believed to work synergistically to improve blood flow and reduce inflammation. We believe that DM199 has the potential to treat several acute and chronic diseases.

Replenishing KLK1 Levels

DM199 therapy is intended to increase production of bradykinin which in turn activates a greater number of the increased bradykinin 2 receptors present in arteries affected by AIS, referred to as the ischemic penumbra, thus improving collateral circulation in the ischemic penumbra. By delivering vital oxygen and nutrients to brain tissues in need, there is the potential to preserve/restore neuronal function and reduce the size of the ischemic penumbra, minimizing tissue death (infarction) and brain damage.

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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, the system which promotes local blood flow and vasodilation and may also mitigate inflammation and oxidative stress by selectively delivering these signaling molecules when and where they are needed.

DM199 and KLK1

DM199 is a synthetic form of the human tissue kallikrein-1 (KLK1) protein. We developed DM199 in part due to the success of forms of KLK1 produced from human urine and pig pancreas in combatting a variety of diseases associated with reduced or low levels of KLK1 in Asia. Our initial focus is on treating acute ischemic stroke (AIS) and cardio-renal disease.

The Potential Therapeutic Effects of KLK1 Replacement

DM199 can be administered intravenously or subcutaneously. It is intended to restore an individual’s KLK1 to normal, healthy levels. KLK1 activates bradykinin receptors, primarily the bradykinin 2 receptor, which stimulates the production of nitric oxide and prostaglandins that, working together, may ultimately improve collateral circulation and stroke outcomes and may reduce blood pressure and maintain or improve kidney function.

DM199's Effect on Hypertension and Kidney Function

KLK1 is believed to promote the dilatation of the efferent arterioles in the kidney, improving micro vascularization and blood flow while reducing hypertension and improving kidney function. 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 believed that KLK1 plays a role in controlling the epithelial sodium channels (ENaC), which regulates the body’s retention or elimination of sodium, a potential problem in patients with salt-sensitive hypertension.

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 associated with KLK1 deficiencies. We believe that DM199 is the only KLK1 protein replacement therapy in clinical development outside of Asia.