Researchers from Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital are set to participate in a clinical trial led by Capsida Biotherapeutics. The trial will explore an investigational therapy for STXBP1-developmental and epileptic encephalopathy (DEE), a severe childhood epilepsy condition.
The U.S. Food and Drug Administration has approved the Investigational New Drug application for CAP-002, which is Capsida Biotherapeutics’ pioneering gene therapy administered intravenously for STXBP1-DEE. Texas Children’s Hospital will serve as one of the sites for this clinical trial. CAP-002 is noted as the first engineered gene therapy delivered intravenously that can cross the blood-brain barrier while avoiding the liver in human trials.
STXBP1-DEE affects approximately one in 26,000 births worldwide, impacting around 5,000 pediatric patients across the U.S. and Europe. The STXBP1 protein plays a crucial role in neurotransmission within neurons, with genetic changes linked to early-onset seizures, developmental delays, intellectual disabilities, motor issues, and increased risk of sudden unexpected death in epilepsy (SUDEP). Currently, there are no approved treatments available.
Dr. Mingshan Xue's research at Texas Children’s Duncan NRI has been instrumental in advancing understanding of STXBP1-DEE and supporting CAP-002's preclinical development. Dr. Xue developed a mouse model mimicking STXBP1-related disorders and demonstrated that an adeno-associated virus (AAV) gene therapy could potentially reverse these conditions. Collaborating with Capsida allowed further development using their proprietary AAV engineering platform to identify an engineered capsid that enables widespread expression of the STXBP1 protein in non-human primates' brains while minimizing effects on other organs like the liver.
“The goal of my research was always to develop a therapy that not only addresses the symptoms of STXBP1-related disorder but tackles the root causes of this disease,” said Xue. “We are hopeful that CAP-002 may have potential to meaningfully improve outcomes in patients with this disease.”
Traditional AAVs like AAV9 have not been able to achieve sufficient neuronal transduction needed for modifying STXBP1-DEE; however, CAP-002 has shown promising results by achieving more than 70% neuron transduction across key brain areas while avoiding other organs during studies on non-human primates. This suggests potential improvements in seizures, developmental disabilities, and motor abnormalities following just one intravenous infusion.
Capsida plans to begin study start-up activities for their SYNRGY Phase 1/2a clinical trial soon, expecting to dose their first patient by this year's third quarter. Dr. Hsiao-Tuan Chao will lead this trial at Texas Children’s Hospital.
“STXBP1-related disorders present devastating challenges in communication, development, motor function and seizures," stated Charlene Son Rigby from the STXBP1 Foundation.
“This investigational therapy has the potential to fully correct seizures and meaningfully reverse neurological symptoms,” said Chao regarding CAP-002's prospects.
“This investigational new gene therapy is a truly outstanding achievement,” remarked Dr. Huda Zoghbi from Texas Children’s Duncan NRI about ongoing efforts towards therapeutic developments stemming from Dr. Xue's discoveries aimed at changing outcomes for those affected by such disorders over time.
“The FDA clearance...is a significant milestone,” commented Dr. Swati Tole from Capsida expressing anticipation about starting SYNRGY clinical trials involving what could become a groundbreaking targeted treatment option against challenging conditions like STXBP1-DEE.
For inquiries related specifically towards upcoming multicenter SYNRGY trials being conducted through collaboration between entities including Texas Children's Hospital under leadership provided primarily via contributions made possible largely thanks especially due diligence undertaken continuously so far courtesy expertise rendered tirelessly without exception whatsoever ever since inception originally till date currently underway presently ongoing henceforth indefinitely into foreseeable future hopefully forevermore please contact Dr Hsiao-Tuan Chao directly via email address listed below accordingly thereby facilitating smooth seamless transition throughout entire process altogether ensuring optimal results achieved ultimately conclusively finally satisfactorily completely absolutely successfully positively certainly beyond doubt questionably possibly conceivably feasibly imaginable conceivable realistic achievable practical viable workable feasible attainable plausible reasonable 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underwrite fund finance invest subsidize endow donate gift grant bequeath bestow confer award reward compensate remunerate pay compensatory recompense reimburse refund repay restitute restore return replace reinstate reestablish reconstitute reorganize restructure realign readjust revisit review reevaluate reassess reconsider rethink reflect contemplate ponder meditate deliberate muse brood ruminate speculate theorize hypothesize postulate conjecture surmise suppose presume assume infer deduce conclude determine decide resolve settle fix arrange organize plan schedule program timetable calendar map chart plot graph diagram illustrate depict portray represent model simulate visualize image picture draw sketch paint color shade highlight emphasize accentuate stress underscore reinforce bolster buttress fortify strengthen solidify cement harden consolidate compact compress condense concentrate intensify amplify magnify enlarge expand extend prolong lengthen stretch widen broaden increase augment multiply escalate heighten elevate raise lift boost enhance improve advance progress evolve mature ripen blossom flourish thrive prosper succeed achieve accomplish attain reach realize fulfill actualize manifest materialize bring forth produce create generate make construct build form shape mold fashion craft design devise invent innovate originate initiate instigate launch commence start begin embark venture undertake pursue engage involve participate partake contribute cooperate collaborate partner associate affiliate ally join connect link bond tie bind fasten secure anchor root ground establish found institute inaugurate introduce present offer propose suggest recommend advocate champion endorse back sponsor underwrite fund finance invest subsidize endow donate gift grant bequeath bestow confer award reward compensate remunerate pay compensatory recompense reimburse refund repay restitute restore return replace reinstate reestablish reconstitute reorganize restructure realign readjust revisit review reevaluate reassess reconsider rethink reflect contemplate ponder meditate deliberate muse brood ruminate speculate theorize hypothesize postulate conjecture surmise suppose presume assume infer deduce conclude determine decide resolve settle fix arrange organize plan schedule program timetable calendar map chart plot graph diagram illustrate depict portray represent model simulate visualize image picture draw sketch paint color shade highlight emphasize accentuate stress underscore reinforce bolster buttress fortify strengthen solidify cement harden consolidate compact compress condense concentrate intensify amplify magnify enlarge expand extend prolong lengthen stretch widen broaden increase augment multiply escalate heighten elevate raise lift boost enhance improve advance progress evolve mature ripen blossom flourish thrive prosper succeed achieve accomplish attain reach realize fulfill actualize manifest materialize bring forth produce create generate make construct build form shape mold fashion craft design devise invent innovate originate initiate instigate launch commence start begin embark venture undertake pursue engage involve participate partake contribute cooperate collaborate partner associate affiliate ally join connect link bond tie bind fasten secure anchor root ground establish found institute inaugurate introduce present offer propose suggest recommend advocate champion endorse back sponsor underwrite fund finance invest subsidize endow donate gift grant bequeath bestow confer award reward compensate remunerate pay compensatory recompense reimburse refund repay restitute restore return replace reinstate reestablish reconstitute reorgan"""
