The Evolution of Retinal Gene Therapy: From Clinical Trials to Clinical Practice

Mutations in a large number of genes cause retinal degeneration and blindness with no cure currently available. Retinal gene therapy has evolved over the last decades to become a promising new treatment paradigm for these rare disorders. This article reflects on the ideas and concepts arising from basic science towards the translation of retinal gene therapy into the clinical realm. It describes the advances and present thinking on the efficacy of current clinical trials and discusses potential roadblocks and solutions for the future of retinal gene therapy.

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Controlling Hypertension and Stroke Prevention – From Guideline to Clinical Practice

Asia Pacific Cardiology ◽

10.15420/apc.2011:3:1:30 ◽

2011 ◽

Vol 3 (1) ◽

pp. 30

Author(s):

Anding Xu ◽

Zefeng Tan ◽

◽

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Clinical Trials ◽

Clinical Practice ◽

Stroke Prevention ◽

Modifiable Risk Factors ◽

Cerebrovascular Events

Hypertension is the most important of the prevalent and modifiable risk factors for stroke. Based on evidence, blood pressure (BP) lowering is recommended in guidelines for the prevention of stroke. However, there are still some uncertainties in the guidelines for controlling BP and preventing stroke in patients with previous cerebrovascular events, such as the goal BP, who to treat and which class of BP-lowering drugs to use. This article discusses these questions by reviewing guidelines and corresponding clinical trials, with the aim of reducing the gap between guidelines and clinical practice.

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ANTIBODY-DRUG CONJUGATES FOR TARGETED CANCER THERAPY

Problems in oncology ◽

10.37469/0507-3758-2019-65-6-777-784 ◽

2019 ◽

Vol 65 (6) ◽

pp. 777-784

Author(s):

David Korman

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Gemtuzumab Ozogamicin ◽

Brentuximab Vedotin ◽

Cytostatic Agent ◽

Cytostatic Agents ◽

Drug Conjugates ◽

Natural Substances ◽

Intracellular Release ◽

High Antitumor Activity

Monoclonal antibody (MAB) conjugates with cytostatic agents (ADC) are intended for selective delivery of a cytostatic agent to a tumor cell. Three ADC have been approved for clinical use (gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab-DM1); a few dozens of other ADC are undergoing clinical trials. Several derivatives of natural substances (antibiotics and inhibitors of microtubules) having a high antitumor activity are used as cytostatic agents included in ADC. They are inapplicable in clinical practice as self-sustained drugs due to their considerable toxicity. Of great importance for the implementation of the ADC effect is the character of a linker connecting MAB with a cytostatic agent and ensuring selective intracellular release after ADC internalization. The structure, mechanisms of action, and the results of clinical trials of a number of ADC are considered here as an illustration (by way of example). The development of ADC can help introduce new effective cytostatic agents into clinical practice.

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Towards More Successful Gene Therapy Clinical Trials for β-Thalassemia

Current Molecular Medicine ◽

10.2174/15665240113139990064 ◽

2013 ◽

Vol 13 (8) ◽

pp. 1314-1330 ◽

Cited By ~ 4

Author(s):

E. Drakopoulou ◽

E. Papanikolaou ◽

M. Georgomanoli ◽

N. Anagnou

Keyword(s):

Gene Therapy ◽

Clinical Trials

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How Far Are Non-Viral Vectors to Come of Age and Reach Clinical Translation in Gene Therapy?

International Journal of Molecular Sciences ◽

10.3390/ijms22147545 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7545

Author(s):

Myriam Sainz-Ramos ◽

Idoia Gallego ◽

Ilia Villate-Beitia ◽

Jon Zarate ◽

Iván Maldonado ◽

...

Keyword(s):

Gene Therapy ◽

Clinical Practice ◽

Gene Delivery ◽

Viral Vectors ◽

Viral Vector ◽

Clinical Success ◽

Genetic Material ◽

Viral Gene ◽

Promising Alternative ◽

Vector Systems

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

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International teleproctoring in neurointerventional surgery and its potential impact on clinical trials in the era of COVID-19: legal and technical considerations

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2020-017053 ◽

2020 ◽

pp. neurintsurg-2020-017053

Author(s):

Emanuele Orru' ◽

Miklos Marosfoi ◽

Neil V Patel ◽

Alexander L Coon ◽

Christoph Wald ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

High Resolution ◽

Situational Awareness ◽

Flow Diverter ◽

Multiple Sources ◽

Remote Supervision ◽

Angiography Suite ◽

The Us ◽

Travel Restrictions

BackgroundExisting travel restrictions limit the mobility of proctors, significantly delaying clinical trials and the introduction of new neurointerventional devices. We aim to describe in detail technical and legal considerations regarding international teleproctoring, a tool that could waive the need for in-person supervision during procedures.MethodsInternational teleproctoring was chosen to provide remote supervision during the first three intracranial aneurysm treatments with a new flow diverter (currently subject of a clinical trial) in the US. Real-time, high-resolution transmission software streamed audiovisual data to a proctor located in Canada. The software allowed the transmission of images in a de-identified, HIPAA-compliant manner.ResultsAll three flow diverters were implanted as desired by operator and proctor and without complication. The proctor could swap between images from multiple sources and reported complete spatial and situational awareness, without any significant lag or delay in communication. Procedural times and radiologic dose were similar to those of uncomplicated, routine flow diversion cases at our institution.ConclusionsInternational teleproctoring was successfully implemented in our clinical practice. Its first use provided important insights for establishing this tool in our field. With no clear horizon for lifting the current travel restrictions, teleproctoring has the potential to remove the need for proctor presence in the angiography suite, thereby allowing the field to advance through the continuation of trials and the introduction of new devices in clinical practice. In order for this tool to be used safely and effectively, highly reliable connection and high-resolution equipment is necessary, and multiple legal nuances have to be considered.

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Impact on actual clinical practice of the latest evidence for percutaneous closure of patent foramen ovale associated with stroke. A single center experience

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.089 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

L Carnero Montoro ◽

M Ruiz Ortiz ◽

N Paredes Hurtado ◽

M Delgado Ortega ◽

A Rodriguez Almodovar ◽

...

Keyword(s):

Clinical Trials ◽

Clinical Practice ◽

Patent Foramen Ovale ◽

Cryptogenic Stroke ◽

Percutaneous Closure ◽

Publication Date ◽

Foramen Ovale ◽

Complex Anatomy ◽

The Mean ◽

The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background and aims Since september 14th, 2017. Three large clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) was associated with lower recurrence in patients with cryptogenic stroke (CS). Our aim was to determine the impact of these findings on routine clinical practice in a tertiary hospital. Methods Patients with percutaneous closure of PFO due to CS (January 2001-January 2020) were included. The clinical characteristics were analyzed individually and grouped in the RoPE score, before and after the publication date. Complex anatomy (CA) defined as interatrial septum aneurysm or basal wide bubble passage was evaluated in both periods. Results 293 patients were included. The mean age was 49 ± 11 years, 15% were older than 60 years, 60% men, 26% hypertensive, 28% smokers and 7%diabetics. The median RoPEscore was 6 [p25-75, 5-7] and 75% met CA criteria. Since september 14th, 2017, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69% p <0.0005 and 51 ± 11 vs. 48 ± 11 years, p = 0.02, respectively), and RoPEscore, significantly lower (5 [5-7] vs. 6 [5-7], p = 0.02). Conclusion The publication of clinical trials wich demonstrated the benefit of percutaneous closure of PFO in CS had a significant impact on the daily clinical practice of our institution, with an increase in indications for CA, despite a clinical profile suggestive of lower causal probability of PFO.

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The United States’ Regulatory Environment Is Evolving to Accommodate a Coming Boom in Gene Therapy Research

Applied Biosafety ◽

10.1177/1535676019854866 ◽

2019 ◽

Vol 24 (3) ◽

pp. 147-152 ◽

Cited By ~ 2

Author(s):

Daniel Eisenman

Keyword(s):

United States ◽

Gene Therapy ◽

Clinical Trials ◽

The United States ◽

Regulatory Environment ◽

Evidence Based ◽

Regulatory Structure ◽

Regulatory Changes ◽

Current State ◽

Therapy Field

Introduction: A dramatic increase in the number of clinical trials involving gene-modified cell therapy and gene therapy is taking place. The field is on the verge of a boom, and the regulatory environment is evolving to accommodate the growth. Discussion: This commentary summarizes the current state of the field, including an overview of the growth. The United States (US) regulatory structure for gene therapy will be summarized, and the evolution of the oversight structure will be explained. Conclusion: The gene therapy field has recently produced its first FDA-approved therapeutics and has a pipeline of other investigational products in the final stages of clinical trials before they can be evaluated by the FDA as safe and effective therapeutics. As research continues to evolve, so must the oversight structure. Biosafety professionals and IBCs have always played key roles in contributing to the safe, evidence-based advancement of gene therapy research. With the recent regulatory changes and current surge in gene therapy research, the importance of those roles has increased dramatically.

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