Collagenase activity in skin fibroblasts of patients with amyotrophic lateral sclerosis

In the current study we have measured collagenase activity released from skin explants and fibroblasts of patients with both Guam-type and sporadic amyotrophic lateral sclerosis and controls. The rationale for such a study derives from work reported more than 20 years ago demonstrating abnormalities in skin collagen metabolism in patients with the disease. We were not able to find significant differences in collagenase activity when fibroblasts were compared relative to the total protein secreted. This is explained, in part, by our finding of an increase in total protein released from fibroblasts of the amyotrophic lateral sclerosis patient group. Increased collagenase release did occur when activity was expressed per number of cells plated but was not statistically significant. In addition, increased release followed a 3-day lag period in skin organ culture. These results suggest that collagenase and other enzymes known to activate collagenase, such as plasminogen activator, capable of degrading extracellular matrix components might be responsible for the increased collagenolytic activity previously observed in amyotrophic lateral sclerosis patients' skin. Further evaluation of extracellular-acting degradative enzymes from skin, muscle, nerve and central nervous system may be important to follow-up such leads in understanding the pathogenesis of this enigmatic and fatal disorder.