N-Palmitoylethanolamine Administration Ameliorates the Clinical Manifestation and Progression of Experimental Autoimmune Encephalomyelitis in Rodents

Abstract

Experimental autoimmune encephalomyelitis in rodents (EAE) is an accepted in vivo model for immunopathogenic mechanisms underlying multiple sclerosis (MS) and tests possible treatment options because it mimics many of the disease patterns. The current treatments for delaying MS progression include cytostatic, immunomodulatory drugs such as mitoxantrone, cyclophosphamide (Cy), biological agents such as interferon (IFN)-beta, natalizumab and random polymer glatiramer acetate. Unfortunately, all of these compounds have potentially serious side effects, some require systemic administration, and the biological agents are costly and immunogenic, causing response failure during prolonged treatment. With this aim in mind, the purpose of the current research was to examine the effects of endogenous substances such as N-palmitoylethanolamine (PEA). PEA is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, anti-inflammatory and neuroprotective mediator, acting at several molecular targets in both central and sensory nervous systems as well as immune cells. The effect of PEA daily administered was investigated in rats and mice developing EAE. A multidisciplinary approach was employed to study behavior and biochemical parameters. In our study we found that PEA counteracts the clinical course and pathology of monophasic EAE in myelin basic protein-immunized Lewis rats and the progression of EAE induced in C57BIA) mice by immunization with myelin oligodendrocyte glycoprotein. Our results show that PEA treatment had a beneficial effect on the two different EAE models.Multiple sclerosis (MS) is an autoimmune disease that affects approximately 400,000 people a year in the US, and more than 2.1 million people worldwide. Genetic, environmental and immunological factors have been linked with the etiology of this disease, but the cause or causes of MS are still unknown (I). Patients suffering from MS develop partial to complete paralysis as well as impaired cogmtrve function. While the exact trigger of MS remains unclear, it is known that the disease involves autoreactive T cells that infiltrate into the central nervous system (CNS) and target myelinated cells. Inflammation, demyelination and axonal damage in the CNS represent manifestation of MS (2).

Endocannabinoid levels in peripheral blood mononuclear cells of multiple sclerosis patients treated with dimethyl fumarate

“…As for 2-AG levels, they experienced a slight increase at 24 months, although it is uncertain whether this gain is directly produced by DMF, as most of the therapeutic effects of the drug are achieved during the first months of therapy and because of the smaller sample size at 24 months. New therapies based on increasing the ECB tone, such as administering exogenous ECBs or hydrolysis inhibitors have demonstrated beneficial anti-inflammatory effects in EAE mice treated with PEA 35 and in murine models of EAE 36 , Alzheimer’s disease 37 , rheumatoid arthritis 38 and airway inflammation 39 treated with inhibitors of the degradative ECB enzymes monoacylglycerol lipase (MAGL), fatty acid amide hydrolase (FAAH) or α/β-hydrolase domain containing 6 (ABHD6).…”