4.5 Article

Central Nervous System Gene Therapy: Present Developments and Emerging Trends Accelerating Industry-Academia Pathways

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Article Biotechnology & Applied Microbiology

Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency

Chun-Hwei Tai et al.

Summary: Gene therapy with eladocagene exuparvovec in patients with aromatic L-amino acid decarboxylase deficiency leads to sustained and meaningful benefits, including improvements in motor and cognitive function, increased dopamine production, symptom relief, improved growth, and enhanced quality of life for patients and caregivers.

MOLECULAR THERAPY (2022)

Article Biochemistry & Molecular Biology

AAV gene therapy for Tay-Sachs disease

Terence R. Flotte et al.

Summary: This study presents the results of AAV gene therapy in two patients with infantile TSD. The treatment was well tolerated without vector-related adverse events, and demonstrated an increase and stability of HexA activity in the cerebrospinal fluid. One patient showed disease stabilization, while the other experienced disease progression after treatment.

NATURE MEDICINE (2022)

News Item Biotechnology & Applied Microbiology

Disruptions in the development of cell and gene therapies

Guang Yang et al.

NATURE REVIEWS DRUG DISCOVERY (2022)

Article Clinical Neurology

Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease Three-Year Outcomes From the PD-1101 Trial

Chadwick W. Christine et al.

Summary: The PD-1101 trial evaluated the long-term safety and clinical outcomes of VY-AADC01 gene therapy in patients with moderately advanced Parkinson's disease. The results showed that VY-AADC01 was well-tolerated and resulted in improved motor function and quality of life, as well as reduced medication requirements over the course of 36 months.

NEUROLOGY (2022)

Review Medicine, General & Internal

Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings

Hau Kiu Edna Au et al.

Summary: Adeno-associated viruses (AAVs) are the safest and most effective gene delivery vehicles in gene therapy, but their translatability into clinical settings is partly limited. This study analyzed over two decades of clinical trial data and found variations in the speed of novel AAV development in different therapeutic areas. More clinical data on dosing regimes, immune-modulation strategies, and gene editing approaches are needed to accelerate the translation of AAV-mediated gene therapy.

FRONTIERS IN MEDICINE (2022)

Review Neurosciences

Gene Therapy for Neurological Disease: State of the Art and Opportunities for Next-generation Approaches

Gareth Morris et al.

Summary: Gene therapy is showing promise in treating rare monogenetic neurological disorders and could potentially offer new treatments for common non-genetic disorders as well. However, the permanent nature of gene therapies may pose risks, and research is being conducted to develop approaches that allow for treatment to be turned on and off.

NEUROSCIENCE (2022)

Editorial Material Immunology

Considerations for the chemistry, manufacturing and Controls (CMC)-quality package for COVID-19 vaccines- interim lessons learnt by the European medicines Agency (EMA)

Ragini Shivji et al.

Summary: This commentary discusses the importance of timely approval and rapid manufacturing capacity for COVID-19 vaccines. It emphasizes the need for early engagement with regulators, understanding key challenges in vaccine production, investing in production and testing site readiness, and planning for the post-approval phase. The European Medicines Agency's experience in facilitating approvals and increasing production capacity is of interest to healthcare professionals, academia, and global regulators.

VACCINE (2022)

Article Biochemistry & Molecular Biology

Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters

Bart Nieuwenhuis et al.

Summary: Adeno-associated viral vectors are commonly used for gene transfer in the nervous system, with promoter and viral vector serotype being key factors in determining transgene expression dynamics. This study compares the effectiveness of four promoters and finds that the mPGK and hSYN promoters result in the strongest transgene expression, with hSYN showing neuron-specific expression including in corticospinal neurons.

GENE THERAPY (2021)

Article Biotechnology & Applied Microbiology

Deep diversification of an AAV capsid protein by machine learning

Drew H. Bryant et al.

Summary: The study uses deep learning to design highly diverse AAV2 capsid protein variants viable for packaging DNA payload, surpassing the average diversity of natural AAV serotype sequences. Deep neural network models accurately predict capsid viability across diverse variants even when trained on limited data, unlocking previously unreachable sequence space with many potential applications.

NATURE BIOTECHNOLOGY (2021)

Review Neurosciences

Gene-based therapies for neurodegenerative diseases

Jichao Sun et al.

Summary: Gene therapy is experiencing a resurgence, particularly in the realm of neurodegenerative diseases, offering the potential to target disease etiology and provide long-term correction. Recent successes in spinal muscular atrophy using gene-based therapies have sparked optimism and highlighted the potential for similar interventions in other neurodegenerative diseases. Advances in viral vectors and genome-engineering tools have opened up new possibilities for diffusely delivering genes throughout the CNS and manipulating disease pathways, paving the way for a future where gene-based therapeutics are integrated into clinical practice.

NATURE NEUROSCIENCE (2021)

Article Clinical Neurology

Engineered microRNA-based regulatory element permits safe high-dose miniMECP2 gene therapy in Rett mice

Sarah E. Sinnett et al.

Summary: The study shows that controlling the overexpression of MECP2 remains a critical obstacle in gene therapy for Rett syndrome. By developing a risk-driven viral genome design strategy and inserting miRARE into the miniMECP2 gene expression cassette, the safety of gene transfer was greatly improved without compromising efficacy, suggesting a potential use in gene therapy for other dose-sensitive genes.
Article Immunology

Overcoming Immunological Challenges Limiting Capsid-Mediated Gene Therapy With Machine Learning

Anna Z. Wec et al.

Summary: The key challenge in making AAV capsid mediated gene therapy widely beneficial is overcoming pre-existing and therapy-induced immune responses. Recent advancements in engineering improved capsid properties have been accelerated by high-throughput DNA synthesis, multiplexing, and sequencing technologies. Utilizing machine learning, viral immunology advancements, and high-throughput measurements can enable the engineering of a new generation of de-immunized capsids for expanding the therapeutic reach of gene therapy.

FRONTIERS IN IMMUNOLOGY (2021)

Article Engineering, Biomedical

AAV manufacturing for clinical use: Insights on current challenges from the upstream process

Terrence Dobrowsky et al.

Summary: rAAV has quickly become a favored viral transfer tool in gene therapy due to its safety and long-term gene expression capabilities. Recent approvals for rAAV molecules in treating congenital amaurosis and spinal muscular atrophy are driving the development of therapeutics for a wider range of indications, highlighting the increasing need for robust manufacturing processes.

CURRENT OPINION IN BIOMEDICAL ENGINEERING (2021)

Editorial Material Pharmacology & Pharmacy

Regulators' Advice Can Make a Difference: European Medicines Agency Approval of Zynteglo for Beta Thalassemia

Martina Schuessler-Lenz et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2020)

Review Biotechnology & Applied Microbiology

AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer

Helena Costa Verdera et al.

MOLECULAR THERAPY (2020)

Article Multidisciplinary Sciences

The once and future gene therapy

Karen Bulaklak et al.

NATURE COMMUNICATIONS (2020)

Article Health Policy & Services

Establishing a reasonable price for an orphan drug

Mikel Berdud et al.

COST EFFECTIVENESS AND RESOURCE ALLOCATION (2020)

Article Clinical Neurology

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease

Chadwick W. Christine et al.

ANNALS OF NEUROLOGY (2019)

Review Clinical Neurology

Therapeutic landscape for Batten disease: current treatments and future prospects

Tyler B. Johnson et al.

NATURE REVIEWS NEUROLOGY (2019)

Review Clinical Neurology

Cholesterol 24-Hydroxylation by CYP46A1: Benefits of Modulation for Brain Diseases

Alexey M. Petrov et al.

NEUROTHERAPEUTICS (2019)

Article Emergency Medicine

The Extended Treatment Window's Impact on Emergency Systems of Care for Acute Stroke

Joseph B. Miller et al.

ACADEMIC EMERGENCY MEDICINE (2019)

Review Clinical Neurology

Gene Therapy for Neurodegenerative Diseases

Vivek Sudhakar et al.

NEUROTHERAPEUTICS (2019)

Article Multidisciplinary Sciences

A systematic capsid evolution approach performed in vivo for the design of AAV vectors with tailored properties and tropism

Marcus Davidsson et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

Article Biotechnology & Applied Microbiology

Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina In Vivo

Livia S. Carvalho et al.

HUMAN GENE THERAPY (2018)

Review Neurosciences

Gene Therapy for Parkinson's Disease, An Update

Tobias M. Axelsen et al.

JOURNAL OF PARKINSONS DISEASE (2018)

Review Biotechnology & Applied Microbiology

Gene therapy for neurological disorders: progress and prospects

Benjamin E. Deverman et al.

NATURE REVIEWS DRUG DISCOVERY (2018)

Article Biotechnology & Applied Microbiology

Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson's Disease

Stephane Palfi et al.

HUMAN GENE THERAPY CLINICAL DEVELOPMENT (2018)

Article Medicine, Research & Experimental

Efficient Gene Transfer to the Central Nervous System by Single-Stranded Anc80L65

Eloise Hudry et al.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2018)

Editorial Material Multidisciplinary Sciences

Repairs for a runaway brain

Liam Drew

NATURE (2018)

Review Engineering, Biomedical

Adeno-associated virus (AAV) vectors: Rational design strategies for capsid engineering

Esther J. Lee et al.

CURRENT OPINION IN BIOMEDICAL ENGINEERING (2018)

Editorial Material Biotechnology & Applied Microbiology

After Glybera's withdrawal, what's next for gene therapy?

Melanie Senior

NATURE BIOTECHNOLOGY (2017)

Article Medicine, General & Internal

Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy

Florian Eichler et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Article Biochemistry & Molecular Biology

Promoter methylation and histone modifications affect the expression of the exogenous DsRed gene in transgenic goats

M. T. Nuo et al.

GENETICS AND MOLECULAR RESEARCH (2016)

Article Medicine, Research & Experimental

Re-examination of regulatory opinions in Europe: possible contribution for the approval of the first gene therapy product Glybera

Natsumi Watanabe et al.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2015)

Article Medicine, Research & Experimental

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

Virginia Haurigot et al.

JOURNAL OF CLINICAL INVESTIGATION (2013)

Review Physiology

Breathing challenges in Rett Syndrome: Lessons learned from humans and animal models

Jan-Marino Ramirez et al.

RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY (2013)

Article Biochemistry & Molecular Biology

Targeted methylation of CMV and E1A viral promoters

Chia-Chen Hsu et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2010)

Article Biotechnology & Applied Microbiology

A Phase I Study of Aromatic L-Amino Acid Decarboxylase Gene Therapy for Parkinson's Disease

Shin-ichi Muramatsu et al.

MOLECULAR THERAPY (2010)

Article Clinical Neurology

Safety and tolerability of putaminal AADC gene therapy for Parkinson disease

C. W. Christine et al.

NEUROLOGY (2009)