RESUMO
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.
Assuntos
Cistatinas/metabolismo , Produtos do Gene tat/metabolismo , Transdução Genética , Síndrome de Unverricht-Lundborg/terapia , Barreira Hematoencefálica , Membrana Celular/fisiologia , Cistatina B , Cistatinas/genética , Cistatinas/uso terapêutico , Inibidores de Cisteína Proteinase , Produtos do Gene tat/genética , Produtos do Gene tat/uso terapêutico , Humanos , Plasmídeos , Ligação Proteica , Transporte ProteicoRESUMO
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.
Assuntos
Epilepsias Mioclônicas Progressivas/etiologia , Epilepsias Mioclônicas Progressivas/genética , Epilepsias Mioclônicas Progressivas/terapia , Adolescente , Adulto , Encéfalo/patologia , Criança , Humanos , Doença de Lafora/complicações , Doença de Lafora/genética , Doença de Lafora/terapia , Síndrome MERRF/complicações , Síndrome MERRF/genética , Síndrome MERRF/terapia , Mucolipidoses/complicações , Mucolipidoses/genética , Mucolipidoses/terapia , Músculo Esquelético/patologia , Epilepsias Mioclônicas Progressivas/complicações , Lipofuscinoses Ceroides Neuronais/complicações , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/terapia , Síndrome de Unverricht-Lundborg/complicações , Síndrome de Unverricht-Lundborg/genética , Síndrome de Unverricht-Lundborg/terapiaRESUMO
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.
