Apertura Gene Therapy and the Rett Syndrome Research Trust (RSRT) have announced a strategic collaboration to advance genetic medicine approaches for Rett syndrome using Apertura's novel blood-brain barrier-crossing technology. The partnership grants RSRT licensing rights to Apertura's human transferrin receptor 1 capsid (TfR1 CapX), an engineered adeno-associated virus (AAV) delivery system designed to overcome one of gene therapy's most significant challenges in treating central nervous system disorders.
Revolutionary Blood-Brain Barrier Technology
Apertura's TfR1 CapX represents a significant advancement in CNS-targeted gene delivery. The intravenously administered AAV capsid is engineered to bind the transferrin receptor 1 (TfR1), a well-characterized receptor that enables efficient transport across the blood-brain barrier. TfR1 maintains broad and consistent expression throughout life, even in neurological disease contexts, making it an attractive target for CNS delivery applications.
Preclinical studies have demonstrated the platform's impressive CNS selectivity, achieving over 50% neuronal transduction and 90% astrocyte transduction across multiple brain regions. This broad cellular coverage is particularly relevant for Rett syndrome, which affects the brain diffusely, suggesting that wider transduction may correlate with greater symptomatic improvement.
Dr. Ben Deverman, Director of Vector Engineering at the Broad Institute and Apertura's academic founder, developed the TfR1 CapX technology. The platform addresses critical limitations in current gene therapy approaches, including the need for more potent and less invasive treatments for CNS disorders.
Addressing Rett Syndrome's Unmet Medical Need
Rett syndrome is a rare genetic neurodevelopmental disorder caused by random mutations in the MECP2 gene on the X chromosome. The condition predominantly affects girls, with symptoms typically becoming apparent between 12 to 18 months of age. The disorder causes devastating developmental regression, depriving toddlers of speech, hand use, and normal movement, often including the ability to walk.
As the condition progresses, patients experience anxiety, seizures, tremors, breathing difficulties, and severe gastrointestinal issues. While cognitive abilities are believed to remain largely intact, most children require total round-the-clock care throughout their lives, with most surviving to adulthood.
"Efficient, safe, and widespread delivery of genetic medicines to the brain is the ultimate goal for treating CNS disorders such as Rett syndrome," said Monica Coenraads, Founder and CEO of RSRT and parent to an adult daughter with Rett. "Successfully addressing this challenge would dramatically accelerate the development of genetic medicines for Rett and other neurological diseases."
Integration with MECP2 Editing Consortium
The collaboration will integrate Apertura's capsid technology into RSRT's MECP2 Editing Consortium, launched in 2024 as part of a broader $40 million "Roadmap to Cures" initiative. The Consortium represents a collaboration among six laboratories developing next-generation genetic medicines for Rett syndrome, with the goal of bringing three genetic medicines beyond current gene therapies to clinical trials by 2028.
The Consortium's editing programs will utilize the Apertura capsid to deliver genetic medicine cargoes diffusely across the brain through non-invasive intravenous administration. The licensing agreement also allows RSRT to sublicense the capsid technology for other Rett syndrome programs, potentially accelerating development across multiple therapeutic approaches.
Industry Partnership Model
"RSRT has made remarkable progress in advancing Rett syndrome therapies, and Apertura is committed to accelerating this momentum with TfR1 CapX," said Diego Garzón, PhD, Vice President of Corporate Development at Apertura Gene Therapy. "Our engineered capsid addresses the critical need for more potent and less invasive treatments, significantly benefiting patients and caregivers."
The collaboration exemplifies how industry partnerships can rapidly advance vital therapies for patients with rare diseases. Apertura, founded in 2021 on technology from the Broad Institute with support from Deerfield Management Company, has positioned itself to develop genetic medicines that overcome limitations in cellular access, gene expression, pre-existing immunity, and manufacturability.
Multiple clinical trials in gene therapy for Rett syndrome are currently underway, all enabled by RSRT-funded research. The organization's exclusive focus on advancing genetic medicines for Rett syndrome has created a robust pipeline of potential treatments, with the new partnership adding a potentially transformative delivery platform to accelerate development timelines.
