New York-based biotech Apertura Gene Therapy has entered a collaboration agreement with the TSC Alliance, a Maryland-based patient advocacy organization, to advance preclinical gene therapy programs for tuberous sclerosis complex using Apertura’s TfR1 CapX platform, an intravenously delivered AAV capsid engineered to cross the blood-brain barrier. The collaboration covers two programs targeting distinct genetic causes of TSC — mutations in the TSC1 and TSC2 genes — both at the preclinical stage. Financial terms were not disclosed.
The TSC1 program is the more advanced of the two. Apertura has received FDA INTERACT feedback endorsing a streamlined preclinical development strategy for that program, and IND-enabling studies are underway. The TSC2 program remains at an earlier preclinical stage; Apertura presented cell-based potency assay data measuring mTOR pathway activity at the American Society of Gene and Cell Therapy annual meeting in 2025.
Deal context
TfR1 CapX is an AAV capsid described by Apertura as engineered to bind human Transferrin Receptor 1, a protein constitutively expressed on brain capillary endothelial cells that form the blood-brain barrier. The capsid is designed to undergo receptor-mediated transcytosis — binding TfR1 on the blood-facing surface of BBB endothelium, crossing the cell, and releasing into the brain parenchyma. The approach is mechanistically distinct from empirically selected capsids such as PHP.eB, which exploit the mouse-specific LY6A receptor and do not translate to non-human primates or humans. Apertura has reported that TfR1 CapX achieves CNS delivery at dose levels approximately 40-fold lower than current CNS gene therapies, with reduced liver accumulation, and has built neutralizing antibody-evading attributes into the capsid shell.
TSC is caused by loss-of-function mutations in either TSC1, encoding hamartin, or TSC2, encoding tuberin. Both proteins form a complex that suppresses mTOR signaling; their loss leads to constitutive mTOR pathway activation, driving the cortical tubers, seizures, intellectual disability, and systemic tumor growth that characterize the disease. Roughly one-third of TSC patients carry TSC1 mutations and two-thirds carry TSC2 mutations, providing the rationale for Apertura’s dual-program structure.
Apertura, a private company backed by Deerfield Management and based at the Cure innovation hub in New York, operates a platform licensing model in which TfR1 CapX serves as a disease-agnostic delivery vehicle loaded with indication-specific gene payloads by partners. The TSC Alliance collaboration follows the same structural template as a previously announced arrangement with the Rett Syndrome Research Trust, in which Apertura applied TfR1 CapX to Rett syndrome programs. Apertura has also signed licensing agreements with AviadoBio, Galibra Neuroscience, and Emugen Therapeutics using the same capsid platform, establishing a pattern of deploying TfR1 CapX across rare CNS diseases through a network of disease-specific partnerships. The company announced a manufacturing collaboration with Viralgen in March 2026 to support GMP-scale production of TfR1 CapX-based programs.
For the TSC Alliance, the collaboration represents an extension of its model of partnering directly with industry to accelerate therapy development for a disease that currently has no approved gene therapy. The mTOR inhibitors everolimus and sirolimus address some TSC manifestations but do not correct the underlying genetic defect.
This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: https://allsci.com/news/
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