Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity

Abstract

Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson’s Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS. However, the effect of carbidopa on T cell responses in vivo is unknown. In this report, we show that carbidopa strongly inhibited T cell activation in vitro and in vivo. Accordingly, carbidopa mitigated myelin oligodendrocyte glycoprotein peptide fragment 35–55 (MOG-35-55) induced experimental autoimmune encephalitis (EAE) and collagen induced arthritis in animal models. The data presented here suggest that in addition to blocking peripheral conversion of levodopa, carbidopa may inhibit T cell responses in PD individuals and implicate a potential therapeutic use of carbidopa in suppression of T cell mediated pathologies.

The Challenge of the Pathogenesis of Parkinson's Disease: Is Autoimmunity the Culprit?

“…Current treatments, including dopamine replacement therapy and alleviating the damage of oxidative stress and inflammation, seem insufficient and are limited in treating PD because most of them have only a therapeutic aim rather than both a therapeutic and prophylactic aim. The in vivo data presented by Zhu et al demonstrated a significant suppression of T cell mediated autoimmunity in carbidopa (one of the classical medicines against PD) treated mice compared with untreated mice ( 103 ). It revealed that to prevent autoimmune disorder in PD would be a new target for drug development.…”

Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson’s Disease

“…Besides levodopa, which results in higher exposer to peripheral dopamine, blocking DDC to avoid peripheral conversion of levodopa to dopamine, might have a profound influence on the immune system. Recently, it has been reported that carbidopa, a DDC inhibitor, has immunosuppressive properties as it prevents T-cell proliferation and T-cell autoimmunity in a mouse model [83]. Furthermore, it has been demonstrated that carbidopa is an AHR-ligand [84], and therefore might play a role in the immune system, as AHR is an important contributor to the adaptive immune system by modulating T-cell differentiation, reviewed recently [85].…”

The use of the Heter-LP algorithm to reposition antibiotics for managing E. coli mastitis in dairy cattle

“…New research has demonstrated that it inhibits early events in T cell activation and promotes the development of anti-in ammatory effects. Thus, it has been suggested as apotential therapeutic for the management and/or treatment in ammatory and autoimmune disorders in humans [53].…”