To investigate the preclinical efficacy of a new investigational drug, leriglitazone, in models of neurodegeneration, neuroinflammation and demyelination/remyelination relevant to X-ALD and to other neuroinflammatory conditions.

Single Abcd1 and double Abcd1/Abcd2 knockouts were used as preclinical models of AMN. The widely used Experimental Autoimmune Encephalomyelitis and the Cuprizone mice models were used to study the potential effects of leriglitazone in neuroinflammation, such as it occurs in cALD, and in enhancing remyelination respectively.  Several in vitro models including a BBB transwell system and human cells from X-ALD patients were used to investigate the brain penetration of leriglitazone and its protective effects in macrophages, neurons, microglia, astrocytes and oligodendrocytes. 

Leriglitazone decreased microglia activation, reversed pro-inflammatory status, prevented early pathological stages that lead to BBB disruption, promoted remyelination by increasing myelination, myelin debris clearance and oligodendrocyte survival. Importantly, leriglitazone influenced progression of neurological disability and reverted motor dysfunction

The preclinical data indicate that leriglitazone is a promising therapeutic approach to treat both CNS phenotypes of X-ALD, AMN and cALD, as well as other neuroinflammatory and/or neurodegenerative diseases.  Lerigltazone is currently in a phase 2/3 clinical trial in AMN in Europe and US, and in two phase 2 trials, in cALD and Friedreich´s Ataxia respectively, in Europe.