Neuroprotection and repair following daily oral administration of 3,5-Diiodothyropropionic acid (DITPA) in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is marked by oligodendrocyte (OL) degeneration and demyelination of the central nervous system (CNS) resulting in significant neurological impairment. The synthetic thyroid hormone (TH) analogue 3,5-diiodothyropropionic acid (DITPA) can bypass Monocarboxylate transporter 8 (MCT8), entering the CNS to effect OL survival and myelination. We identified that downregulated MCT8 during neuroinflammation can be treated through the oral administration of DITPA, during onset and/or peak disease. This treatment can limit neurological decline during experimental autoimmune encephalomyelitis (EAE), positively impacting locomotor outcomes. DITPA–treated mice exhibited improved OL survival, along with reduced myelin and axonal damage during EAE. Mechanistically, DITPA increased AKT-mTOR-PANK2 (pantothenic acid kinase 2) signalling leading to Co Enzyme A and lipid synthesis activation in the CNS. Moreover, DITPA improved myelinated fibre integrity and remyelination. DITPA effectively protects the CNS from neuroinflammatory degeneration, promote OL survival and myelin repair, representing a promising therapeutic candidate for MS.