deCODE submits first-in-class anti-atherosclerosis compound
initiate a Phase I clinical trial of the first-in-class treatment
of peripheral arterial occlusive disease (PAOD) which represents a
promising therapeutic approach to a disease affecting over 10 per
cent of the adult population.
Preclinical studies revealed that DG401 was a selective and potent antagonist of the EP3 receptor for prostaglandin E2 (PGE2), inhibiting, in a dose-dependent manner, human platelet aggregation induced in vitro by PGE2.
EP3 has been identified as a target in PAOD which has linked variations in the gene encoding EP3 to an increase in the risk of the disease. Pending clearance by the FDA, deCODE intends to initiate a Phase I clinical trial of DG041 this spring.
DG-041's mechanism of action involves the inhibition of human platelet aggregation induced by PGE2, in a dose-dependent manner. DG041 has also been shown to protect against intravascular coagulation in a model based on prostanoid-induced platelet activation.
DG041 has also been shown to have minimal effect on bleeding time in animal studies, nor does it inhibit the effect of other platelet agonists such as adenosine diphosphate (ADP), collagen, thrombin or epinephrine.
"To our knowledge, DG041 is the first compound ever developed specifically to target the product of a gene isolated in a common disease," commented Kari Stefansson, CEO of deCODE.
"The genetics pointed us to the fundamental role of EP3 in the development and progression of the atherosclerotic lesions that cause PAOD"
EP3 receptors may also be important modulators of pain transmission. Stefansson said the company also planned to evaluate the potential of compounds targeting EP3 as alternatives to COX-2 inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of chronic pain.
Peripheral arterial occlusive disease, or PAOD, is a vascular disorder that affects over 10 per cent of the adult population in the industrialized world and one in five people over the age of 70.
Symptoms include intermittent pain in the legs while walking or exercising, due to the narrowing by atherosclerotic plaques of one or more major arteries in the legs.
The disease is under-diagnosed, and the current mainstay of treatment is surgery to bypass the occluded vessels. At present, no drug treatment is available that targets the underlying causes of PAOD or prevents its progression.
