New discoveries in progressive myoclonus epilepsies: a clinical outlook

ABSTRACT

Introduction: Progressive myoclonus epilepsies (PMEs) constitute a rare and heterogeneous group of genetic disorders with a distinctive triad of myoclonus, seizures, and progressive neurological deterioration. PMEs, even though rare, are arguably the severest form of epilepsies accounting for <1% of all epilepsies with age at onset varying from infancy to adulthood, depending on the disease. A majority are inherited as autosomal recessive traits, however rare types following autosomal dominant and mitochondrial inheritance are also present.

Areas covered: This review discusses the genetics, molecular pathogenesis, and diagnosis of six major forms of PMEs, the current pharmacological interventions under practice and alternative treatment strategies. It also provides an update on the contemporary attempts, such as gene therapy, for etiological treatment of PMEs. Finally, it comments on the autophagy and lysosomal dysfunction, which has emerged as a unifying mechanism underlying the neurodegeneration in PMEs.

Expert commentary: Despite the tremendous progress made in identifying the defective genes and dissecting their functional pathways, no etiological treatment is currently available. Thus, an integrated approach to personalized medicine with new drugs, gene therapy, and enzyme replacement therapy hold the promise in pursuit of neurotherapeutic treatment of PMEs.

KEYWORDS:

• Autophagy
• enzyme replacement
• gene therapy
• genetics
• ion channel blockers
• myoclonus
• neurodegeneration
• neuroinflammation
• prenatal diagnosis
• seizures

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the Department of Biotechnology, Government of India.