New York-based Apertura Gene Therapy has entered a Cooperative Research and Development Agreement with two NIH institutes to advance preclinical Niemann-Pick disease gene therapy using its proprietary TfR1 CapX capsid — a deal that reflects the NIH's continued institutional commitment to gene-based approaches for a fatal pediatric lysosomal disorder.
The multi-year CRADA involves the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Human Genome Research Institute (NHGRI). The Ara Parseghian Medical Research Fund, a patient advocacy foundation, will contribute financial support. Financial terms were not disclosed, consistent with the non-commercial nature of CRADA arrangements.
What the deal covers
The collaboration focuses on preclinical development of intravenous delivery of TfR1 CapX in combination with a therapeutic gene construct targeting Niemann-Pick disease Type C1 (NPC1), a rare autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 gene. The disease causes progressive neurodegeneration, cerebellar ataxia, and dementia, with death typically occurring in adolescence.
TfR1 CapX is an engineered AAV capsid described by Apertura as designed to bind transferrin receptor 1 (TfR1), a protein constitutively expressed on brain capillary endothelial cells that form the blood-brain barrier. By exploiting receptor-mediated transcytosis, the capsid is intended to cross the blood-brain barrier following intravenous administration and achieve broad CNS distribution — a meaningful advantage over intrathecal or intracranial delivery routes that carry greater procedural complexity. The capsid was developed from technology originated at the Broad Institute by Dr. Ben Deverman, Apertura's scientific founder.
The collaboration also builds on longstanding NIH expertise in NPC1. NICHD Senior Investigator Forbes D. Porter, a principal investigator on the CRADA, has led clinical studies of NPC1 treatments including early cyclodextrin trials and has co-authored preclinical gene therapy work in NPC1 mouse models.
The principal goal is to identify a capsid-construct combination suitable for progression through pre-IND regulatory review and ultimately clinical testing. Parties may expand the scope of the collaboration if preclinical results support further development.