prinomastat and Macular-Degeneration

Prinomastat (formerly AG3340, Agouron Pharmaceuticals, Inc.) is a potent, selective oral inhibitor of matrix metalloproteinase-2, -9, -13 and -14. This peculiar selectivity should represent an advantage for prinomastat in terms of efficacy/tolerability. The drug has been shown to inhibit tumour growth and angiogenesis in a variety of preclinical models, including cancer of colon, breast, lung and intriguingly in melanoma and glioma models. Moreover, the combination of prinomastat and several chemotherapeutic agents was shown to induce additive effects. The drug is currently in Phase III clinical trials for patients with non-small cell lung cancer in combination with paclitaxel and carboplatin, as well as in advanced hormone refractory prostate cancer in combination with mitoxantrone. The most common side effects are musculoskeletal pain and stiffness. These side effects generally cease with treatment interruption. Finally, considering the pathophysiology of MMPs, Agouron is exploring the utility of prinomastat in ophthalmology and dermatology.

Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Glioblastoma; Humans; Macular Degeneration; Metalloendopeptidases; Neovascularization, Pathologic; Organic Chemicals

To identify factors affecting visual acuity and its decrease in eyes with subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD).. Distance visual acuity was recorded at screening and up to five follow-up visits during the first year of a randomized, double-blind, placebo-controlled trial of oral prinomastat. Subjects had AMD in both eyes and neovascular AMD in at least one eye. Analysis employed a generalized linear mixed model.. Of 158 eligible subjects (age 56-90), 125 (79.1%) received prinomastat. Visual acuity was independently affected by relative acuity of the fellow eye, whether the study eye had been the first or second to develop CNV, age, current smoking, leakage area, and prior photocoagulation. Decrease in visual acuity score, unaffected by prinomastat, was less steep in eyes that had been second to develop CNV. Such eyes had a comparable time since CNV onset to other study eyes.. Fellow eye features independently affect visual acuity and its decrease in eyes with classic neovascular AMD.

Topics: Aged; Aged, 80 and over; Choroidal Neovascularization; Double-Blind Method; Female; Humans; Longitudinal Studies; Macular Degeneration; Male; Middle Aged; Organic Chemicals; Placebo Effect; Treatment Outcome; Visual Acuity

Topics: Adult; Angiogenesis Inhibitors; Antineoplastic Agents; Choroidal Neovascularization; Corneal Neovascularization; Diabetic Retinopathy; Endothelial Growth Factors; Eye Diseases; Humans; Infant, Newborn; Intercellular Signaling Peptides and Proteins; Lymphokines; Macular Degeneration; Metalloendopeptidases; Neovascularization, Pathologic; Organic Chemicals; Platelet-Derived Growth Factor; Pregnadienediols; Retinal Neovascularization; Retinopathy of Prematurity; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors