release factor 3 degradation enhances aminoglycoside mediated translational readthrough at mecp2 nonsense mutations

Original title: “Release factor 3 degradation enhances aminoglycoside-mediated translational readthrough at MECP2 nonsense mutations.”

fenfluramine in rett syndrome a multidimensional clinical study

Original title: “Fenfluramine in Rett syndrome: A multidimensional clinical study.”

heterozygous variant in the gabbr2 gene in a girl with clinical classic rett syndrome

Original title: “A Heterozygous Variant in the GABBR2 Gene in a Girl With Clinical Classic Rett Syndrome.”

automated machine vision based index for rett syndrome provides a generalizable framework for modeling rare disease therapeutics

Original title: “An automated machine vision-based index for Rett Syndrome provides a generalizable framework for modeling rare disease therapeutics.”

global literature review of comorbidities and concomitant supportive medications among individuals with rett syndrome

Original title: “A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome.”

family quality of life in the context of rett syndrome insights from brazilian families

Original title: “Family quality of life in the context of Rett syndrome: insights from Brazilian families.”

pilot study the impact of simulation based pediatric basic life support training on the performance of caregivers of children with rett syndrome

Original title: “Pilot study: the impact of simulation-based pediatric basic life support training on the performance of caregivers of children with Rett syndrome.”

The company also reported that ... the gene therapy product. Neurogene plans to have enrolled 8 patients in the low-dose cohort by the end of the year and expects to report updated data in the second half of next year. In the first half of 2025, the company also anticipates that it will release more information on its plan for a registrational clinical trial for NGN-401. ... NGN-401 had been selected as part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics ... The company also reported that it has reached an accord with the FDA regarding plans for scaling up manufacturing and its potency assay strategy for the gene therapy product. Neurogene plans to have enrolled 8 patients in the low-dose cohort by the end of the year and expects to report updated data in the second half of next year. In the first half of 2025, the company also anticipates that it will release more information on its plan for a registrational clinical trial for NGN-401. ... NGN-401 had been selected as part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.2 The program will provide sponsors with the opportunity for frequent advice and regular communication as needed with regard to clinical trial design and other development issues particular to the investigational product being evaluated. The company noted that most treatment-related AEs that occurred in this group have been responsive to steroids and resolved or are resolving. Notably, an SAE was reported in a third patient who was more recently treated in the high-dose cohort. Neurogene pointed out that the SAE is consistent with the known risks of AAV vector-based gene therapy. Alongside the announcement of the interim data, Neurogene stated that a third cohort in the trial, which will treat up to 3 patients aged 16 years or older at the high dose, has been initiated. Notably, Neurogene also stated that it has made the decision to discontinue the development of NGN-101, its investigational AAV vector-based gene therapy intended to treat neuronal ceroid lipofuscinosis (Batten) Subtype 5 (CLN5) disease, which is currently being assessed in · a phase 1/2 clinical trial (NCT05228145).1 Neurogene cited the FDA’s denial of its application for regenerative medicine advance therapy designation for NGN-101 as the reason for the decision, as the company considered this designation necessary for continued investment in the product’s development. Neurogene’s NGN-401, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Rett syndrome, has generated positive efficacy results in the low-dose cohort of aphase 1/2 pediatric clinical trial (NCT05898620), but an emerging treatment-related serious adverse event (SAE) was reported in a patient treated in the study’s high-dose cohort.1

Original title: “Neurogene’s Rett Syndrome Gene Therapy NGN-401 Demonstrates Efficacy in Low-Dose Cohort, But Serious Adverse Event in High-Dose Group Raises Concerns | CGTlive®”

New FDA Pilot Program Will Provide Hands-On Regulatory Guidance for Cell and Gene Therapy Trials in Rare Disease · Neurogene also announced in June 2024 that NGN-401 had been selected as part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.2 ... New FDA Pilot Program Will Provide Hands-On Regulatory Guidance for Cell and Gene Therapy Trials in Rare Disease · Neurogene also announced in June 2024 that NGN-401 had been selected as part of the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program.2 The program will provide sponsors with the opportunity for frequent advice and regular communication as needed with regard to clinical trial design and other development issues particular to the investigational product being evaluated. We look forward to participating in this landmark effort with the FDA as we seek to rapidly advance NGN-401 toward a potential registrational study for the patients and families who live with this devastating disease.” · NGN-401 is being evaluated in a phase 1/2 clinical trial (NCT05898620). As of June 2024, the therapy has been well-tolerated in treated study participants, with all treatment-related adverse events (AEs) being mild and transient or resolving. NGN-401 is being evaluated in an early phase clinical trial which has been selected for the FDA’s START Pilot Program. ... “We appreciate the FDA’s ongoing commitment to expedite development of our NGN-401 gene therapy for Rett syndrome, with RMAT designation following NGN-401’s selection for the FDA’s START Pilot Program, 2 synergistic initiatives designed to more rapidly advance promising treatments for patients with unmet medical needs,” Rachel McMinn, PhD, Founder and Chief Executive Officer, Neurogene, said in a statement.1 “RMAT and START designations underscore the therapeutic potential of NGN-401 for Rett syndrome and reflect our commitment to accelerate development of NGN-401. There have also been no treatment-emergent or intracerebroventricular (ICV) procedure-related serious AEs.3 · “We have met an important program milestone of initiating dosing in the high-dose cohort of our Rett syndrome gene therapy trial, and we are pleased to share that high-dose NGN-401 has been well-tolerated thus far with an early favorable safety profile,” McMinn said in a statement at that time.3 “We intentionally designed NGN-401 with the goal of creating a best-in-class treatment option by leveraging what we believe to be the optimal route of administration to deliver consistent and tightly controlled full-length MECP2 expression to key areas of the brain and nervous system, and today’s safety update underscores NGN-401’s potential to deliver on that profile.

Original title: “Rett Syndrome Gene Therapy Adds RMAT Designation to the List | CGTlive®”

Neurogene also relayed new preclinical findings on the use of intracerebroventricular and intrathecal lumbar delivery of NGN-401. received regenerative medicine advanced therapy (RMAT) designation from the FDA and was selected for the FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program.2,3 Higher expression in key brain regions was seen with the ICV method both when ICV and IT-L used a dose that approximates the dose being used in human patients in the phase 1/2 trial (1 x 1015 vg) and when the IT-L method used a dose approximately 4 times higher than the clinically relevant dose being used with the ICV method. Neurogene also highlighted that in peripheral organs such as the liver, peripheral exposure of vector genome biodistribution was comparable to equivalent ICV and IT-L doses. “Feedback from the Rett syndrome community and key opinion leaders reinforces that the decision Importantly, the comparable systemic exposure between ICV and IT-L confirms there is no liver-sparing benefit to IT-L administration, consistent with clinical data from intra–cerebrospinal fluid administered products.” · Notably, in November 2024, a patient treated with NGN-401 in the phase 1/2 study · was reported to be in critical condition following a serious adverse event (SAE).4,5 The SAE, which · was previously reported by Neurogene as an emerging treatment-related SAE consistent with the known risks of AAV vector-based gene therapy, was then described as constituting signs of a rare and life-threatening immune response known as a systemic hyperinflammatory syndrome. Neurogene has finished talks with the FDA regarding the protocol for the registrational Embolden clinical trial to evaluate NGN-401, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Rett syndrome.1

Original title: “Neurogene Reaches Accord With FDA on Plan for Registrational Trial for Rett Syndrome Gene Therapy NGN-401 | CGTlive®”

Taysha also disclosed that it has received written alignment from the FDA on elements of a potential BLA strategy for TSHA-102. We expect to complete dosing across our REVEAL and ASPIRE trials in the second quarter of 2026. With an estimated 15,000 to 20,000 patients affected by Rett syndrome across the United States, European Union, and United Kingdom and compelling REVEAL Part A clinical data, we see a significant opportunity to redefine the treatment paradigm for this devastating disease with high unmet need.” “Breakthrough therapy designation highlights the FDA’s recognition of both the significant unmet medical need across the estimated 10,000 patients suffering from Rett syndrome in the United States and the potential of TSHA-102 to redefine the treatment paradigm for this devastating disease,” Rumana Haque-Ahmed, the chief regulatory officer of Taysha, said in an October 2025 statement.2 “This designation was granted following the FDA’s review of available clinical data from the 12 patients treated in part A of our REVEAL trials, which support the potential of TSHA-102 to improve function and enable achievement of developmental milestones across core areas of disease that may significantly impact patient and caregiver lives. Taysha Gene Therapies has dosed the first patient in the pivotal phase 3 portion (Part B) of the REVEAL clinical trial (NCT05606614), which is assessing the investigational adeno-associated virus (AAV) vector–based gene therapy TSHA-102 for the treatment of Rett syndrome.¹ In conjunction with the dosing announcement, Taysha disclosed that it has received written alignment from the FDA on elements of a potential biologics license application (BLA) strategy for TSHA-102. This alignment pertains to a separate planned clinical trial, ASPIRE (NCT identifier pending), which will evaluate the gene therapy in 3 girls aged 2 to less than 4 years.

Original title: “Pivotal Trial for Taysha's Rett Syndrome Gene Therapy TSHA-102 Doses First Patient | CGTlive®”