Résumé :
|
In late November 2006, GENETHON initiated its first gene therapy clinical trial in gamma-sarcoglycanopathy (LGMD2C), a rare autosomal recessive muscular disorder caused by mutations in the gamma-sarcoglycan gene. Patients commonly present with proximal and progressive muscular weakness before the age of 10 and loose ambulance by age 12 on average. Cardiomyopathy and respiratory insufficiency may develop during the course of the disease, leading to poor prognosis and premature death. Earlier during the clinical development, GENETHON had obtained an Orphan Drug Designation by EMEA. Approval from the French Agencies was obtained in November 2006 to initiate the phase I/IIa trial, which is being held at Pitié–Salpêtrière Hospital in Paris. The investigational product, a serotype 1 adeno-associated virus (AAV1) vector harboring the human gamma-sarcoglycan gene, is administered by a single intramuscular injection into the carpi radialis muscle. The primary objective of this trial is to evaluate the clinical safety of local intramuscular injection of the gene therapy product. Secondary objectives are to monitor local and systemic immune responses, assess histological modifications and gene transfer into injected muscles. 9 patients, aged above 15, will be enrolled sequentially in the study, assigned to 3 cohorts with a single dose-escalation and followed-up for 6 months. Evaluation will address clinical, histological, biological, immunological and functional parameters as well as MRI. As of today, four patients have been treated. The first cohort has been completed and the first patient of the second cohort has been treated. Encouraging data will be presented on the status of the product activity, immunologic response and patient compliance to the treatment. As the clinical trial is halfway, a next phase IIb clinical trial is being planned, in which systemic administration will be performed. This implies important preclinical and clinical points to consider, as well as a series of preclinical studies to achieve.
|