Dihydrofolate Reductase Inhibition

Dihydrofolate reductase (DHFR) is an enzyme involved in cellular replication and activation. Methotrexate, the active component of ADX-2191, is a DHFR inhibitor, which has been used to treat cancer and autoimmune disease. The anti-proliferative and anti-inflammatory properties of DHFR inhibition are well described.

Application to Proliferative Vitreoretinopathy, an Inflammatory Retinal Disease

Proliferative vitreoretinopathy (PVR) is characterized by excessive replication and pro-inflammatory activity of retinal cells, at least a portion of which synthesize collagen, the principal component of scar tissue. Retinal scarring can lead to impairment of vision, including blindness. In preclinical studies of primary cell cultures from PVR patients, DHFR inhibition reduced pathological cell proliferation and scar-like collagen deposition. The observed clinical activity of our investigational new drug ADX-2191 in PVR is believed to be the result of the down-regulation of aberrant retinal cell proliferation and activity, thereby leading to reduced retinal scarring.