2026-05-13 | Industry Insights: Regulatory progress and AI-driven advances in nucleic acid therapeutics
Across March and April 2026, activity in the nucleic acid therapeutics field reflected broad regulatory momentum and continued clinical advancement across multiple RNA modalities. Regulatory highlights included US FDA Priority Review designations for Ionis' antisense oligonucleotide (ASO) zilganersen in Alexander disease, alongside EMA acceptance of GSK's marketing authorisation application for the ASO bepirovirsen in chronic hepatitis B. Clinical milestones featured first-in-human trials of novel modalities, including Alltrna's transfer RNA therapeutic AP003 and AIRNA's RNA-editing candidate AIR-001. AI-driven discovery also advanced, with Asimov launching an integrated RNA optimisation platform and ProQR partnering with Ginkgo Bioworks to scale high-throughput data generation for its RNA editing pipeline.
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2025-12-15 | Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants.
Glial Fibrillary Acidic Protein (GFAP) is a key intermediate filament protein critical for maintaining the structural integrity and function of astrocytes in the central nervous system. Mutations in GFAP are the root cause of Alexander disease (AxD), a rare and often fatal neurodegenerative disorder characterized by elevation of GFAP levels and accumulation of GFAP in the form of Rosenthal fibers. Here, we outline a comprehensive set of experimental approaches for the biochemical characterization of GFAP and its disease-causing variants. Using optimized expression and advanced purification techniques, we achieved high yields and purity of both wild-type and mutant GFAP proteins. Biochemical assays were employed to evaluate the effects of pathogenic mutations on filament assembly, solubility, and aggregation. Additionally, we explored the role of aberrant posttranslational modifications in GFAP aggregation and their impact on filament properties. This work advances our understanding of GFAP's role in AxD and lays a foundation for developing therapeutic strategies targeting GFAP dysfunction. Furthermore, the methodologies presented here serve as valuable tools for investigating the biochemical consequences of GFAP mutations and advancing interventions for GFAP-related disorders.
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2025-09-29 | Description of the Hamburg Alexander Leukodystrophy Cohort—Insights into Practical Classification and the Care Situation
Background: Alexander disease (AxD) is a rare severe leukodystrophy that has no cure to date. A pathogenic gain-of-function variant in the GFAP gene affects the astrocytes and subsequently the function of the white matter in the CNS. Methods: We retrospectively analyzed the most frequent symptoms of nine AxD cases, classified them according to published classifications, and described the need of care and support. Results: The description of the courses of disease of nine cases with AxD reflects the broad spectrum of different phenotypes of AxD, with often occurring apnoea. Data about care and support for AxD patients indicate a high and heterogeneous need of support. Treatment with steroids reduced symptoms in two patients. Some patients showed lasting improvement during their course of disease. Conclusions: The course of AxD is very heterogeneous. Thus, we extracted relevant key features to describe the severity of the disease, namely feeding problems, epilepsy, age-appropriate motor function, failure to thrive, age-appropriate language and apnoea. We recommend early evaluation for clinical care and support. For some AxD patients, treatment with steroids may alleviate symptoms. Further development of efficient treatments is necessary.
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