The potential of LINGO-1 as a therapeutic target for essential tremor

Abstract

Introduction: LINGO-1 is a negative regulator of neuronal survival, oligodendrocyte differentiation and axonal outgrowth and regeneration, because it interacts with diverse growth factor receptors blocking or inhibiting their action. Consistent findings obtained in vitro and in animal models suggest that anti-LINGO-1 therapy may be useful in neurodegenerative disorders such as multiple sclerosis (MS), Parkinson’s disease or essential tremor (ET). Moreover, genetic and pathological evidence provide a robust link between LINGO-1 and ET.

Areas covered: In this review, we present an overview of current knowledge on findings linking LINGO-1 and ET, with a special focus on genetic linkage, we include an overview of LINGO1 gene variations according to the 1000 genomes catalog, and we identify potential gene areas where common changes occur because, as well as the risk developing ET, LINGO1 genetic changes may influence the response to anti-LINGO-1 therapy.

Expert opinion: The goal of anti-LINGO-1 therapy in neurodegenerative diseases is to ease the brakes of neuronal growth and recovery. An anti-LINGO-1 antibody is under clinical trials for MS patients. Before planning trials with ET patients, refinement on the genetic link between LINGO1 and ET, and a detailed genetic and phenotypic assessment of ET patients to be enrolled, should be carried out.

Keywords:

• BIIB033
• clinical trials
• essential tremor
• genetic linkage
• Li81
• LINGO-1

Declaration of interest

The authors were supported by Grants PI12/00241, PI12/00324 and RETICS RD12/0013/0002 from Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain, and GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union. The authors receive writing assistance from James McCue, University of Extremadura. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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