In-house production of lentiviral gene therapy for Pompe disease

Project summary

Pompe disease is a monogenic lysosomal storage disorder (LSD) caused by deficiency of acid alpha glucosidase (GAA), leading to glycogen accumulation that primarily affects skeletal muscles and, in most severe cases, the heart and brain. Enzyme replacement therapy (ERT) offers benefit, but requires life-long (bi)weekly 4-6 hr infusions, does not halt disease progression, cannot treat the brain and is extremely expensive.

We have developed hematopoietic stem and progenitor cell-mediated lentiviral gene therapy (HSPC-LVGT) for Pompe disease that is able to fully rescue pathology in heart, skeletal muscles, and brain in a mouse model. To bring gene therapy to patients, we have founded the startup LentiCure. LentiCure aims to solve the current market failure of gene therapies for rare diseases – caused by extremely high prices driven by profit over relatively few patients – via in-house development according to a non-for-profit business model.

The purpose of the current proposal is to develop the cell process at the ATMP facility of Erasmus MC for the first in human study of lentiviral gene therapy for Pompe disease. In a unique collaboration between the hospital ATMP, gene therapy experts, LentiCure, and experienced external CROs, we will develop cost effective culture, lentiviral transduction, cryopreservation and thawing of HSPCs to establish regulatorycompliant new technology that adheres to the highest requirements for market authorization, including the use of a closed cell processing system (Prodigy). We will perform scaled test runs and prepare an initial gene therapy product for the first 2 patients with Pompe disease. The cell process will be documented for endorsement by the EMA and FDA, and will also be disseminated as part of a blueprint for in-house development of gene therapy. Applied here to Pompe disease, the cell process pipeline will be suitable for future in-house development of gene therapies for other disorders.