Translarna (ataluren) / PTC Therapeutics - LARVOL DELTA

Enhancement of CFTR nonsense mutation readthrough via combined small molecule and ACE-tRNA therapies (NACFC 2026) - "These approaches encompass small molecules that influence translation termination, including PTC124, aminoglycosides (e.g., G418), and release factor degraders such as SRI-41315 and CC-90009. These findings support our hypothesis that reducing the competition for ACE-tRNA binding to PTCs results in increased potency and/or efficacy. Consequently, the co-administration of ACE-tRNAs and eRF1/eRF3 degraders could mitigate the delivery burden of ACE-tRNAs necessary for CFTR restoration. Ongoing studies are focused on evaluating the functional rescue of CFTR following these combination treatments in comparison to monotherapy."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

NMD Inhibition Unlocks Readthrough-Free Modulator Rescue of Nonsense Variants in CFTR at TM12-NBD2: A G551D-Like Precision Path (NACFC 2026) - "While readthrough drugs were advanced to clinical trials (e.g., Ataluren, ELX- 02) to enable translation past PTCs and suppress NMD, these trials have failed to show meaningful benefit...In primary airway cultures (W1282X/W1282X, n = 4; S1255X, n = 1), activity improved from ∼0.1 to 3.4–3.9 μA/cm2 with KVS0001 + next-generation modulators (VTI/Alyftrek) ( ∼27% of WT), with similar rescue using ETI (Trikafta) or ivacaftor-based regimens... Taken together, for TM12–NBD2-proximal nonsense variants, NMD inhibition alone without readthrough agents unlocks clinically available modulator rescue, offering a path to expand therapy to pwCF currently who currently have no options. Because NMD is a core transcriptome surveillance pathway, large-animal PK/tox studies in a CFTR PTC reporter SRM2 pig model are warranted. Establishing this NMD-first model for PTC variants could provide a framework for treating all PTC variants."

Cystic Fibrosis • Genetic Disorders • Immunology • Respiratory Diseases

Synthesis of Pyridin-2(1H)-ones and Isoquinolin-1(2H)-ones Using Calcium Carbide as an Acetylene Source under Redox-Neutral Conditions. (PubMed, Org Lett) - "On the basis of this method, a number of pyridin-2(1H)-one and isoquinolin-1(2H)-one derivatives, including some hybrid products containing the essential skeleton of probenecid, ataluren, or adapalene, were obtained. In general, this protocol features simple and economical substrates, a safe and convenient acetylene source, the absence of an external oxidant, good compatibility with labile functional groups, excellent step and atom economy, and ready scalability. Moreover, some products possess strong anticancer activities."

Journal • Hepatitis C • Infectious Disease • Oncology

PTC124 promotes mutation site-dependent readthrough of STK11 nonsense mutations and restores tumor suppressor function. (PubMed, BBA Adv) - "Pharmacological inhibition of AMPK attenuated these effects, further supporting that the antitumor activity of PTC124 is mediated through the STK11-AMPK signaling axis. Collectively, these findings highlight the therapeutic potential of nonsense mutation readthrough strategies and suggest that PTC124 may serve as a precision medicine approach for cancers harboring STK11 nonsense mutations."

Journal • Oncology • STK11

Recalibrating Therapeutic Priorities for Duchenne Muscular Dystrophy: A Critical Synthesis of Approved and Emerging Strategies Through the Lens of an Underrepresented Population. (PubMed, Genes (Basel)) - "We argue that the conventional priority ordering (gene therapy first, exon-skipping second, standard care as background) does not hold up when weighed against patient-relevant outcomes and cost, and may reasonably be inverted for resource-limited systems. This is our interpretation of an indirect comparison, not an evidence-based clinical recommendation. On that reading, the highest-value investments for Central Asia are early molecular diagnosis, universal access to glucocorticoids and specialised physiotherapy, and individual-import pathways for ataluren, while AAV gene therapy is, in our view, a lower near-term priority until its durability and safety data improve."

Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Patient-derived cornea organoids as drug repurposing models for aniridia-associated keratopathy. (PubMed, Life Sci) - "This study presents patient-specific organoid models for AAK using iPSCs and offers insight into mutation effects and PAX6 restoration following drug repurposing. The findings form the basis of personalized treatments for congenital aniridia."

Journal • Ophthalmology • PAX6

Real-World Ataluren Outcomes in 7 nmDMD Patients (ICNMD 2026) - "A notable finding is the high frequency of intellectual disability (71%) of patients and learning difficulties in 85%. Cognitive impairments may influence adherence to treatment and rehabilitation, and performance in timed motor assessments, increasing variability in longitudinal functional outcomes. Overall, the data suggest that long-term ataluren treatment in routine clinical practice is feasible and may be associated with preserved cardiac function during adolescence, with some patients maintaining ambulation into their mid-teens."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • Cognitive Disorders • Developmental Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Mental Retardation • Muscular Dystrophy

Study of Pembrolizumab combined with Ataluren in Patients with metastatic pMMR and dMMR colorectal cancer adenocarcinomas or metastatic dMMR endometrial carcinoma: the ATAPEMBRO study (clinicaltrialsregister.eu) - P1/2 | N=47 | Completed | Sponsor: Amsterdam UMC | Active, not recruiting ➔ Completed

dMMR • pMMR • Trial completion • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Oncology • Solid Tumor

Ion-Channel-Mediated Drug Repurposing Opportunities Validated by Single-Cell Perturbation in Colorectal Cancer. (PubMed, Int J Mol Sci) - "Immune checkpoint receptors (LAG3, CD27) connect via PPI intermediates to Ca2+ and K+ channels, targetable by relatlimab (FDA-approved) and varlilumab (Phase 2). This work maps previously unknown links between CRC driver genes and ion channel regulation, with the ataluren-RPS21-KCNQ2 axis ready for pharmacological testing."

IO biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • CD27 • LAG3

Identification of novel small molecule compounds with readthrough activity in Nagashima-type palmoplantar keratosis. (PubMed, J Dermatol Sci) - "Our research identified new compounds that effectively promote the readthrough of premature stop codons. In vitro, these compounds showed higher readthrough potency than drugs such as gentamicin or ataluren. These results suggest that these compounds could be promising therapeutic agents for genetic diseases caused by nonsense mutations."

Journal • Genetic Disorders • SERPINB7

Efficacy and Safety of Ataluren in Duchenne Muscular Dystrophy Due to Nonsense Mutation: A Systematic Review and Meta-analysis of Randomized Controlled Trials (AAN 2026) - "Although findings suggest potential clinical benefit, the limited number of RCTs and short follow-up durations warrant cautious interpretation. Larger, long-term, multicenter trials are required to better define ataluren’s therapeutic role in nmDMD."

Retrospective data • Review • CNS Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases

Rescuing TP53 from nonsense: novel triazoles for translational readthrough via optimized drug design. (PubMed, Sci Rep) - "All four compounds successfully rescued p53 expression in H1299 R213X cells, outperforming Ataluren and matching G418 at significantly lower concentrations. The restored p53 exhibited nuclear localization upon genotoxic stress and induced transcription of canonical targets. These findings highlight the therapeutic potential of these compounds for treating TP53 nonsense mutations in cancer and lay the groundwork for the development of targeted nonsense mutation-specific treatment for a wide range of pathologies, including new emergent p53 related diseases."

Journal • Oncology • TP53

Genetic, Clinical, and Management Characteristics of Duchenne Muscular Dystrophy in Saudi Arabia. (PubMed, Healthcare (Basel)) - "Age of diagnosis and age of treatment initiation is relatively late in the KSA. However, early diagnosis and early treatment onset is associated with better clinical outcomes, mainly a delay in LoA. Therefore, there is an urgent need for raising awareness and enhancing early screening in the KSA."

Clinical • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Inflammation • Muscular Dystrophy

Cost-Utility Analysis of the Treatment With Ataluren Plus Standard of Care Compared With Standard of Care Alone in Patients With Duchenne Muscular Dystrophy in Brazil. (PubMed, Value Health Reg Issues) - "Ataluren plus SoC for treating nonsense mutation Duchenne muscular dystrophy patients was not a cost-effective intervention compared with SoC alone from the perspective of the Brazilian public health system."

HEOR • Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • Rare Diseases

Ataluren for the treatment of people living with nonsense mutation Duchenne muscular dystrophy: a plain language summary of Study 041. (PubMed, J Comp Eff Res) - P3 | "This study is the largest phase 3 clinical study of people living with nmDMD that has been done so far. ClinicalTrials.gov, NCT number: NCT03179631."

Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD) (clinicaltrials.gov) - P3 | N=270 | Completed | Sponsor: PTC Therapeutics | Enrolling by invitation ➔ Completed | Trial completion date: Apr 2025 ➔ Feb 2026 | Trial primary completion date: Apr 2025 ➔ Feb 2026

Trial completion • Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

Mutation type-specific transcriptomic signatures and readthrough therapy rescue in SMC1A-related developmental and epileptic encephalopathy. (PubMed, Epilepsia) - "These findings demonstrate that SMC1A-related epileptic encephalopathies are driven by variant-specific molecular mechanisms and highlight the therapeutic promise of ataluren for DEE85. The study supports further development of precision medicine strategies targeting nonsense variants in SMC1A, with potential implications for improving diagnosis, treatment, and quality of life in affected individuals."

Journal • CNS Disorders • Epilepsy • SMC1A

Beyond readthrough: ataluren restores mitochondrial function and reduces oxidative stress in FANCA-mutated cells via mTOR-DRP1 modulation. (PubMed, Cell Death Discov) - "Notably, these beneficial effects persisted under immune stimulation, where ataluren mitigated the metabolic and oxidative burden imposed by lymphocyte activation. Our findings unveil a pleiotropic role for ataluren that extends beyond its canonical readthrough activity, highlighting its potential as a metabolic modulator for FA and possibly other DNA repair-deficient disorders."

Journal • Aplastic Anemia • Hematological Disorders • Metabolic Disorders • FANCA • mTOR

Registry of Translarna (Ataluren) in Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) (clinicaltrials.gov) - P=N/A | N=316 | Completed | Sponsor: PTC Therapeutics | Active, not recruiting ➔ Completed

Trial completion • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

PTC Therapeutics Provides Regulatory Update on Translarna (PRNewswire) - "PTC Therapeutics, Inc...announced..that it has withdrawn the New Drug Application (NDA) resubmission for Translarna (ataluren) for the treatment of nonsense mutation Duchenne muscular dystrophy (DMD) following U.S. Food and Drug Administration (FDA) feedback on the application review...'FDA shared that based on its review to date, the data in the NDA submission are unlikely to meet the Agency's threshold of substantial evidence of effectiveness to support approval of Translarna.'"

FDA event • Duchenne Muscular Dystrophy

Patient reported outcome measures in spinal muscular atrophy and duchenne muscular dystrophy: review of instruments and their inclusion in clinical and regulatory processes. (PubMed, Neurol Sci) - "Despite the availability of PROMs, ObsROMs, and CROMs for SMA and DMD, their use in clinical trials and regulatory documents is limited and inconsistent. Greater standardization and systematic inclusion of these measures are needed to support patient-centered drug development and evaluation."

Journal • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Beyond the stop: Oxadiazole TRIDs restore LRBA protein expression in nonsense-driven primary immunodeficiency. (PubMed, Mol Ther Nucleic Acids) - "Following the recent market withdrawal of ataluren, the only approved translational readthrough-inducing drug (TRID), there is an urgent need for alternative therapeutic options...However, network analysis revealed poor connectivity among differentially expressed proteins, with LRBA unrelated to any regulated cluster. These findings highlight the reported molecules as promising candidates for precision therapy in LRBA deficiency and shed light on the broader cellular impact of TRIDs."

Journal • Immunology • Primary Immunodeficiency

PTC…reported progress with its drug development pipeline. (Investing.com) - "The company reached alignment with the FDA on the design of a global Phase 3 trial for votoplam in Huntington’s disease, planned to initiate in the first half of 2026. The FDA confirmed openness to a potential Accelerated Approval pathway...The company’s New Drug Application for Translarna remains under FDA review."

FDA event • New P3 trial • Duchenne Muscular Dystrophy • Huntington's Disease

CFTR rescue in W1282X cystic fibrosis patient-derived intestinal organoids (PDIOs) mediated by translational readthrough-inducing drugs (TRIDs). (PubMed, Genet Med Open) - "Our studies highlighted the positive effect of NV848 on patient organoid swelling, improving CFTR channel function, whereas NV914 and NV930 did not induce organoid swelling, similar to PTC124 treatment. By leveraging patient-derived intestinal organoids, our findings showed that NV848, in combination with Elexacaftor-Tezacaftor-Ivacaftor and the nonsense-mediated mRNA decay inhibitor NMDI14, enhances CFTR activity. This contributes to the development of personalized therapies for individuals with rare CFTR variants, addressing a critical unmet need in cystic fibrosis treatment."

Journal • Cystic Fibrosis • Genetic Disorders • Immunology • Pulmonary Disease • Respiratory Diseases • CFTR

Duchenne Muscular Dystrophy in the Republic of North Ossetia-Alania: Epidemiological Study, Diagnostic Issues, and Treatment Prospects. (PubMed, Genes (Basel)) - "The heterogeneity of mutation spectrum across different populations underscores the influence of ethnic background. Consequently, this study highlights the importance of population-specific studies for improving DMD care."

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy