Estudo fase 1 da terapia gênica utilizando um vetor viral em pacientes com distrofia muscular de Duchenne
USA – nesta pesquisa inicial os pacientes receberam no braço uma injeção intramuscular com o vetor viral carregando o gene da distrofina; no outro braço eles receberam uma injeção salina. O estudo não tinha objetivo de tratar mas sim observar as reações, efeitos colaterais, dose e segurança do tratamento.
O resumo em inglês do tratamento pode ser lido abaixo:
(Molecular Therapy, 2011) Phase 1 Gene Therapy for Duchenne Muscular Dystrophy Using a Translational Optimized AAV Vector
Dawn E Bowles, Scott WJ McPhee, Chengwen Li, Steven J Gray, Jade J Samulski, Angelique S Camp, Juan Li, Bing Wang, Paul E Monahan, Joseph E Rabinowitz, Joshua C Grieger, Lakshmanan Govindasamy, Mavis Agbandje-McKenna, Xiao Xiao and R Jude Samulski – USA
Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a rational design strategy. AAV2.5 was generated from the AAV2 capsid with five mutations from AAV1. The novel chimeric vector combines the improved muscle transduction capacity of AAV1 with reduced antigenic crossreactivity against both parental serotypes, while keeping the AAV2 receptor binding. In a randomized double-blind placebo-controlled phase I clinical study in DMD boys, AAV2.5 vector was injected into the bicep muscle in one arm, with saline control in the contralateral arm. A subset of patients received AAV empty capsid instead of saline in an effort to distinguish an immune response to vector versus minidystrophin transgene. Recombinant AAV genomes were detected in all patients with up to 2.56 vector copies per diploid genome. There was no cellular immune response to AAV2.5 capsid. This trial established that rationally designed AAV2.5 vector was safe and well tolerated, lays the foundation of customizing AAV vectors that best suit the clinical objective (e.g., limb infusion gene delivery) and should usher in the next generation of viral delivery systems for human gene transfer.
