ABSTRACT
In this work we analysed the characteristics of the cell-permeable peptide TAT-PTD fused to cystatin B (CSTB) to evaluate its potential for protein therapy of Unverricht-Lundborg (UL) epilepsy. TAT-PTD-CSTB does not penetrate the cells despite initial evidence of time and concentration-dependent transduction. Therefore, it cannot be used as a form of replacement of the intracytoplasmic protein missing in UL. Importantly, we discuss precautions to avoid false-positive results when working with TAT-PTD for protein therapy of neurological diseases.
Subject(s)
Cystatins/metabolism , Gene Products, tat/metabolism , Transduction, Genetic , Unverricht-Lundborg Syndrome/therapy , Blood-Brain Barrier , Cell Membrane/physiology , Cystatin B , Cystatins/genetics , Cystatins/therapeutic use , Cysteine Proteinase Inhibitors , Gene Products, tat/genetics , Gene Products, tat/therapeutic use , Humans , Plasmids , Protein Binding , Protein TransportABSTRACT
The progressive myoclonic epilepsies (PMEs) are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. Challenges with PME arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment. Recent advances in molecular genetics have helped achieve better understanding of the different disorders that cause PME. We review the PMEs with emphasis on updated genetics, diagnosis, and therapeutic options.
Subject(s)
Myoclonic Epilepsies, Progressive/etiology , Myoclonic Epilepsies, Progressive/genetics , Myoclonic Epilepsies, Progressive/therapy , Adolescent , Adult , Brain/pathology , Child , Humans , Lafora Disease/complications , Lafora Disease/genetics , Lafora Disease/therapy , MERRF Syndrome/complications , MERRF Syndrome/genetics , MERRF Syndrome/therapy , Mucolipidoses/complications , Mucolipidoses/genetics , Mucolipidoses/therapy , Muscle, Skeletal/pathology , Myoclonic Epilepsies, Progressive/complications , Neuronal Ceroid-Lipofuscinoses/complications , Neuronal Ceroid-Lipofuscinoses/genetics , Neuronal Ceroid-Lipofuscinoses/therapy , Unverricht-Lundborg Syndrome/complications , Unverricht-Lundborg Syndrome/genetics , Unverricht-Lundborg Syndrome/therapyABSTRACT
PURPOSE: A 34-year-old woman with progressive myoclonus epilepsy of Unverricht-Lundborg type was considered for vagus nerve stimulation (VNS) therapy. METHODS: After demonstration of intractability to multiple antiepileptic regimens and progressive deterioration in cerebellar function, the patient was implanted with a vagus nerve stimulator and followed for 1 year. Neurological status, seizure frequency, and parameter changes were analyzed. RESULTS: VNS therapy resulted in reduction of seizures (more than 90%) and a significant improvement in cerebellar function demonstrated on neurological examination. The patient reported improved quality of life based in part on her ability to perform activities of daily living. CONCLUSIONS: VNS therapy may be considered a treatment option for progressive myoclonus epilepsy. The effects of VNS on seizure control and cerebellar dysfunction may provide clues to the underlying mechanism(s) of action.
