Raphael Schiffmann, MD, of 4D Molecular Therapeutics. Schiffmann, discusses why the US Food and Drug Administration (FDA) put a hold on a phase 1 / 2 clinical trial testing 4D-310, a gene therapy in development that targets the heart in Fabry disease.

Globotriaosylceramide buildup causes Fabry disease, which affects multiple body parts. Symptoms include acroparesthesias, angiokeratomas, hypohidrosis, corneal opacity, and hearing loss. Severe complications may lead to kidney damage, heart attack, and stroke. Mutations in the GLA gene cause Fabry disease, inherited through an X-linked pattern. Treatment options include enzyme replacement therapy, pain medications, ACE inhibitors, and renal transplantation.

4D-310 uses a targeted and evolved AAV vector C102 to deliver a codon-optimized human GLA transgene directly to cardiomyocytes and kidney glomeruli cell-autonomous AGA production following IV administration.

A clinical trial assessing the safety and efficacy of 4D-310 was recently put on hold due to reports of treatment-related serious adverse events of atypical hemolytic uremic syndrome (aHUS). In all three cases, aHUS resolved within two to four weeks.

For more information about Fabry disease and other genetic diseases, visit checkrare.com/diseases/congenital-and-genetic-conditions/.