Long-term neurologic and cardiac correction by intrathecal gene therapy in Pompe disease.
Acta Neuropathol Commun
; 5(1): 66, 2017 09 06.
Article
em En
| MEDLINE
| ID: mdl-28874182
ABSTRACT
Pompe disease is a lysosomal storage disorder caused by acid-α-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year. We demonstrate a significant functional neurologic correction in treated animals from 4 months onward, a neuromuscular improvement from 9 months onward, and a correction of the hypertrophic cardiomyopathy at 12 months. The regions most affected by the disease i.e. the brainstem, spinal cord, and the left cardiac ventricular wall all show enzymatic, biochemical and histological correction. Muscle glycogen storage is not affected by the treatment, thus suggesting that the restoration of muscle functionality is directly related to the CNS correction. This unprecedented global and long-term CNS and cardiac cure offer new perspectives for the management of patients.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Doença de Depósito de Glicogênio Tipo II
/
Alfa-Glucosidases
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França