A preliminary investigation of phoshodiesterase 7 inhibitor VP3.15 as therapeutic agent for the treatment of experimental autoimmune encephalomyelitis mice

We examined neuropathology of spinal cord, ex vivo lymphocyte proliferation by [3H]-thymidine incorporation, TNFα by ELISA and cAMP-PDE mRNAs expression by in situ hybridization histochemistry (ISHH) in spinal cord of EAE mice treated with both PDE7 inhibitors. Treatment of EAE mice with the novel PDE7i, VP3.15 showed more efficacy in reducing clinical signs at 10mgkg−1 than the other PDE7i, BRL50481 and similar to fingolimod. VP3.15 acts on peripheral lymphocytes inhibiting their proliferation and TNFα secretion in a dose-dependent manner. PDE7i treatment alters the levels of PDE4B and PDE7 mRNA expression in EAE mice spinal cord. Given the interest in the development of new drugs for MS, including PDE7i as anti-inflammatory drugs, it is important to study the role played by PDE7 in neurodegenerative diseases with inflammatory component to better understand the beneficial and detrimental effects of a future therapy. Graphical abstract
Source: Journal of Chemical Neuroanatomy - Category: Neuroscience Source Type: research