Marked increase in cyclooxygenase-2 in ALS spinal cord - Implications for therapy

Objective: To evaluate the hypothesis that cyclooxygenase-2 (COX-2) is link ed to the pathology of ALS by determining whether COX-2 m-RNA levels are up regulated in ALS spinal cord. Methods: Spinal cord from 11 ALS cases and 27 controls consisting of 15 cases of Alzheimer disease (AD), six cases of Pa rkinson disease (PD), three cases of cerebrovascular disease, and three con trol cases were analyzed. Total RNA was extracted and reverse transcriptase -PCR analysis performed for the mRNA of COX-2, COX-1, the microglial marker CD11b, and the housekeeping gene cyclophilin. Results: In ALS compared wit h non-ALS spinal cord, COX-2 mRNA was upregulated 7.09-fold (p < 0.0001), C OX-1 1.14-fold (p = 0.05), and CD11b 1.85-fold (p = 0.0012). COX-2 mRNA lev els in AD, PD, cerebrovascular disease, and control cases were each signifi cantly lower than in ALS and were not significantly different from each oth er. Western blots of the protein products were in general accord with the m RNA data, with COX-2 protein levels being upregulated 3.79-fold compared wi th non-ALS cases (p = 0.015). Conclusions: The strong upregulation of COX-2 mRNA in ALS is in accord with studies in the superoxide dismutase transgen ic mouse model in which COX-2 upregulation occurs. Taken in conjunction wit h evidence of a neuroprotective effect of COX-2 inhibitors in certain anima l models and in organotypic cultures, the data are supportive of a possible future role for COX-2 inhibitors in the treatment of ALS.