Clinical trial design in gene therapy for neurodegenerative diseases: Sanfilippo A syndrome

Gene therapy (GT) represents a new therapeutic modality particularly suited for untreatable monogenic inherited genetic diseases. An important aspect in GT clinical trial design is the holistic view of the patient and disease. New regulatory guidances provide a framework for continuously evolving clinical trial design in GT and the nature of an intended therapeutic effect often requires unique designs. We present an example of an integrated clinical trial design for a GT (genetically modified AAV-9 containing the cDNA of the human sulfamidase gene) targeting Sanfilippo A syndrome (SFAS), a devastating neurodegenerative disease. With optimized delivery of the GT to the main target organ of SFAS, i.e., the brain (by using the intracerebroventricular administration), the trial design with multiple types of pre-defined complementary measures allows for an integrated assessment of safety/tolerability, pharmacodynamics/biomarkers and efficacy overtime, with the ultimate goal of a comprehensive view of an individual patient’s response characterization.

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