John Libbey Eurotext

Unverricht-Lundborg disease Volume 18, supplément 2, September 2016

1 Epilepsy Unit, Hôpital Gui-de-Chauliac, Research Unit ‘Movement Disorders’ (URMA), Department of Neurobiology, Institute of Functional Genomics, Montpellier, France
2 Magna Graecia University of Catanzaro, Department of Medical and Surgical Sciences, Italy
3 Neurophysiopathology and Epilepsy Centre IRCCS Foundation C. Besta Neurological Institute, Milan, Italy
4 Hopital Henri-Gastaut, Marseille, France
5 Department of Neurology, EPS Charles-Nicolle, Tunis, Tunisia
6 University of Eastern Finland, Kuopio, Finland
7 Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Finland
8 Department of Pathology, Boston Children's Hospital, Boston, USA
9 University of Eastern Finland, Kuopio, Finland
10 San Raffaele Hospital, Milan, Italy
11 Department of Pharmacology, University of Tartu, Tartu, Estonia
* Correspondence: Maria K. Lehtinen Department of Pathology, Boston Children's Hospital, Boston, USA

We first review the clinical presentation and current therapeutic approaches available for treating Unverricht-Lundborg disease (ULD), a progressive myoclonus epilepsy. Next, we describe the identification of disease causing mutations in the gene encoding cystatin B (CSTB). A Cstb-deficient mouse model, which recapitulates the key features of ULD including myoclonic seizures, ataxia, and neuronal loss, was generated to shed light on the mechanisms contributing to disease pathophysiology. Studies with this model have elucidated the diverse biological roles for Cstb from functioning as a protease inhibitor, to regulating glial activation, oxidative stress, serotonergic neurotransmission, and hyperexcitability. These findings set the stage for future studies that may open avenues to improved therapeutic approaches.