scholarly journals Digital Technology in Somatic and Gene Therapy Trials of Pediatric Patients With Ocular Diseases: Protocol for a Scoping Review (Preprint)

2018 ◽  
Author(s):  
Edward Meinert ◽  
Abrar Alturkistani ◽  
Tasnime Osama ◽  
Celine-Lea Halioua-Haubold ◽  
Josip Car ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Personalized Medicine ◽  
Pediatric Patients ◽  
Pediatric Ophthalmology ◽  
Ocular Diseases ◽  
Cell Therapies ◽  
Gene Therapies ◽  
Therapeutic Tools ◽  
The Individual

BACKGROUND Pharmacogenomics suggests that diseases with similar symptomatic presentations often have varying genetic causes, affecting an individual patient’s response to a specific therapeutic strategy. Gene therapies and somatic cell therapies offer unique therapeutic pathways for ocular diseases and often depend on increased understanding of the genotype-phenotype relationship in disease presentation and progression. While demand for personalized medicine is increasing and the required molecular tools are available, its adoption within pediatric ophthalmology remains to be maximized in the postgenomic era. OBJECTIVE The objective of our study was to address the individual hurdles encountered in the field of genomic-related clinical trials and facilitate the uptake of personalized medicine, we propose to conduct a review that will examine and identify the digital technologies used to facilitate data analysis in somatic and gene therapy trials in pediatric patients with ocular diseases. METHODS This paper aims to present an outline for Healthcare Information Technology and Information and Communication Technology resources used in somatic and gene therapy clinical trials in children with ocular diseases. This review will enable authors to identify challenges and provide recommendations, facilitating the uptake of genetic and somatic therapies as therapeutic tools in pediatric ophthalmology. The review will also determine whether conducting a systematic review will be beneficial. RESULTS Database searches will be initiated in September 2018. We expect to complete the review in December 2019. CONCLUSIONS Based on review findings, the authors will summarize methods used for facilitating IT integration in personalized medicine. Additionally, it will identify further research gaps and determine whether conducting further reviews will be beneficial. INTERNATIONAL REGISTERED REPOR PRR1-10.2196/10705

scholarly journals The Promise and the Hope of Gene Therapy

2021 ◽  
Vol 3 ◽  
Author(s):  
Eleni Papanikolaou ◽  
Andreas Bosio
Keyword(s):  
Gene Therapy ◽  
Hemopoietic Stem Cell ◽  
Cell Therapies ◽  
Gene Therapies ◽  
Monogenic Diseases ◽  
Car T ◽  
The Everyday ◽  
Cell Gene ◽  
Stem Cell Gene Therapy

It has been over 30 years since visionary scientists came up with the term “Gene Therapy,” suggesting that for certain indications, mostly monogenic diseases, substitution of the missing or mutated gene with the normal allele via gene addition could provide long-lasting therapeutic effect to the affected patients and consequently improve their quality of life. This notion has recently become a reality for certain diseases such as hemoglobinopathies and immunodeficiencies and other monogenic diseases. However, the therapeutic wave of gene therapies was not only applied in this context but was more broadly employed to treat cancer with the advent of CAR-T cell therapies. This review will summarize the gradual advent of gene therapies from bench to bedside with a main focus on hemopoietic stem cell gene therapy and genome editing and will provide some useful insights into the future of genetic therapies and their gradual integration in the everyday clinical practice.

scholarly journals Digital Technology in Somatic and Gene Therapy Trials of Pediatric Patients With Ocular Diseases: Protocol for a Scoping Review

10.2196/10705 ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. e10705
Author(s):  
Edward Meinert ◽  
Abrar Alturkistani ◽  
Tasnime Osama ◽  
Celine-Lea Halioua-Haubold ◽  
Josip Car ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Scoping Review ◽  
Digital Technology ◽  
Pediatric Patients ◽  
Ocular Diseases

scholarly journals Learning to Personalize Medicine from Aggregate Data

2020 ◽  
Author(s):  
Rich Colbaugh ◽  
Kristin Glass
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Prediction Models ◽  
Predictive Analytics ◽  
Learning Algorithm ◽  
Individual Characteristics ◽  
Training Data ◽  
Experimental Therapy ◽  
Individual Level ◽  
The Individual

AbstractThere is great interest in personalized medicine, in which treatment is tailored to the individual characteristics of patients. Achieving the objectives of precision healthcare will require clinically-grounded, evidence-based approaches, which in turn demands rigorous, scalable predictive analytics. Standard strategies for deriving prediction models for medicine involve acquiring ‘training’ data for large numbers of patients, labeling each patient according to the outcome of interest, and then using the labeled examples to learn to predict the outcome for new patients. Unfortunately, labeling individuals is time-consuming and expertise-intensive in medical applications and thus represents a major impediment to practical personalized medicine. We overcome this obstacle with a novel machine learning algorithm that enables individual-level prediction models to be induced from aggregate-level labeled data, which is readily-available in many health domains. The utility of the proposed learning methodology is demonstrated by: i.) leveraging US county-level mental health statistics to create a screening tool which detects individuals suffering from depression based upon their Twitter activity; ii.) designing a decision-support system that exploits aggregate clinical trials data on multiple sclerosis (MS) treatment to predict which therapy would work best for the presenting patient; iii.) employing group-level clinical trials data to induce a model able to find those MS patients likely to be helped by an experimental therapy.

scholarly journals Ocular Gene Therapy with Adeno-associated Virus Vectors: Current Outlook for Patients and Researchers

2020 ◽  
Author(s):  
Geoffrey A. Casey ◽  
Kimberly M. Papp ◽  
Ian M. MacDonald
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Editing ◽  
Gene Replacement ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
Gene Therapies ◽  
Ocular Disorders ◽  
Adenoassociated Virus ◽  
Underlying Mechanisms

In this “Perspective”, we discuss ocular gene therapy – the patient’s perspective, the various strategies of gene replacement and gene editing, the place of adenoassociated virus vectors, routes of delivery to the eye and the remaining question - “why does immunity continue to limit efficacy?” Through the coordinated efforts of patients, researchers, granting agencies and industry, and after many years of pre-clinical studies, biochemical, cellular, and animal models, we are seeing clinical trials emerge for many previously untreatable heritable ocular disorders. The pathway to therapies has been led by the successful treatment of the RPE65 form of Leber congenital amaurosis with LUXTURNATM. In some cases, immune reactions to the vectors continue to occur, limiting efficacy. The underlying mechanisms of inflammation require further study, and new vectors need to be designed that limit the triggers of immunity. Researchers studying ocular gene therapies and clinicians enrolling patients in clinical trials must recognize the current limitations of these therapies to properly manage expectations and avoid disappointment, but we believe that gene therapies are well on their way to successful, widespread utilization to treat heritable ocular disorders.

scholarly journals Engineered T cell therapies

2015 ◽  
Vol 17 ◽  
Author(s):  
Anne-Christine Field ◽  
Waseem Qasim
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
T Cell ◽  
Viral Vector ◽  
Ex Vivo ◽  
Immune Disorders ◽  
Clinical Experiences ◽  
Cell Therapies ◽  
Cell Gene

Alongside advancements in gene therapy for inherited immune disorders, the need for effective alternative therapeutic options for other conditions has resulted in an expansion in the field of research for T cell gene therapy. T cells are easily obtained and can be induced to divide robustly ex vivo, a characteristic that allows them to be highly permissible to viral vector-mediated introduction of transgenes. Pioneering clinical trials targeting cancers and infectious diseases have provided safety and feasibility data and important information about persistence of engineered cells in vivo. Here, we review clinical experiences with γ-retroviral and lentiviral vectors and consider the potential of integrating transposon-based vectors as well as specific genome editing with designer nucleases in engineered T cell therapies.

Cardiac disease: Current approaches to gene therapy

2020 ◽  
pp. 62-75
Author(s):  
Reyad ul-ferdous ◽  
◽  
Shofiul Azam ◽  
◽  
◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Gene Delivery ◽  
Cardiac Disease ◽  
Target Genes ◽  
Viral Vector ◽  
Delivery Methods ◽  
Gene Therapies ◽  
Inherited Cardiomyopathies

Background: Last decade over the world, the cardiac disease becomes a leading cause of death. Gene-based therapies become a promising treatment for patients affected by cardiovascular diseases, such as myocardial infarction (MI), arteriosclerosis, heart failure and so on, but also underline the require for reproducible results in preclinical and clinical studies for efficacy and safety. Aim: This book chapter describes the current research prospect of gene therapy for cardiac disease. We focus on the various models to deliver genes using viral, non-viral vector, delivery methods, targets gene, recent clinical trials, inherited cardiomyopathies target genes and Present advances of CRISPR/Cas 9 for cardiovascular gene therapy. We recapitulate some challenges that require being overcome, future directions of gene therapies for cardiac disease. Materials and Methods: All required information regards Lef-7 was generated by exploring the internet search engine like as (PubMed, Wiley, ScienceDirect, CNKI, ACS, Google Scholar, Web of Science, SciFinder, and Baidu Scholar) and libraries. Results: In this book chapter, we focus on the present prospect of gene targets, gene delivery methods, and efficient vector to deliver gene, targets gene, recent clinical trials, inherited cardiomyopathies target genes and present advances of CRISPR/Cas 9 technology for the treatment of cardiac disease using gene therapy. Recent clinical trials require modifying vectors and gene delivery approaches to achieve effective results for cardiac gene therapy. Conclusion: In this book chapter, we integrate a historical perspective with recent advances that will likely affect clinical development in this research area.

scholarly journals Personalized Medicine Based on Nasal Epithelial Cells: Comparative Studies with Rectal Biopsies and Intestinal Organoids

2021 ◽  
Vol 11 (5) ◽  
pp. 421
Author(s):  
Iris A. L. Silva ◽  
Violeta Railean ◽  
Aires Duarte ◽  
Margarida D. Amaral
Keyword(s):  
Clinical Trials ◽  
Personalized Medicine ◽  
Unmet Need ◽  
Rare Mutations ◽  
Intestinal Organoids ◽  
Bona Fide ◽  
The Individual ◽  
Rectal Biopsies ◽  
Effective Drugs ◽  
Cftr Modulators

As highly effective CFTR modulator therapies (HEMT) emerge, there is an unmet need to find effective drugs for people with CF (PwCF) with ultra-rare mutations who are too few for classical clinical trials and for whom there are no drug discovery programs. Therefore, biomarkers reliably predicting the benefit from CFTR modulator therapies are essential to find effective drugs for PwCF through personalized approaches termed theranostics. Here, we assess CFTR basal function and the individual responses to CFTR modulators in primary human nasal epithelial (pHNE) cells from PwCF carrying rare mutations and compare these measurements with those in native rectal biopsies and intestinal organoids, respectively, in the same individual. The basal function in pHNEs shows good correlation with CFTR basal function in rectal biopsies. In parallel, CFTR rescue in pHNEs by CFTR modulators correlates to that in intestinal organoids. Altogether, results show that pHNEs are a bona fide theranostic model to assess CFTR rescue by CFTR modulator drugs, in particular for PwCF and rare mutations.

scholarly journals GENE THERAPY FOR OBSTETRIC CONDITIONS

2014 ◽  
Vol 25 (3-4) ◽  
pp. 147-177
Author(s):  
REBECCA N. SPENCER ◽  
DAVID J. CARR ◽  
ANNA L. DAVID
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Lipoprotein Lipase ◽  
Molecular Mechanisms ◽  
Viral Vector ◽  
Genetic Disorders ◽  
Genetic Diseases ◽  
Nasopharyngeal Cancer ◽  
New Paradigm ◽  
Gene Therapies

The first clinical trials of gene therapy in the 1990s offered the promise of a new paradigm for the treatment of genetic diseases. Over the decades that followed the challenges and setbacks which gene therapy faced often overshadowed any successes. Despite this, recent years have seen cause for renewed optimism. In 2012 Glybera™, an adeno-associated viral vector expressing lipoprotein lipase, became the first gene therapy product to receive marketing authorisation in Europe, with a licence to treat familial lipoprotein lipase deficiency. This followed the earlier licensing in China of two gene therapies: Gendicine™ for head and neck squamous cell carcinoma and Oncorine™ for late-stage nasopharyngeal cancer. By this stage over 1800 clinical trials had been, or were being, conducted worldwide, and the therapeutic targets had expanded far beyond purely genetic disorders. So far no trials of gene therapy have been carried out in pregnancy, but an increasing understanding of the molecular mechanisms underlying obstetric diseases means that it is likely to have a role to play in the future. This review will discuss how gene therapy works, its potential application in obstetric conditions and the risks and limitations associated with its use in this setting. It will also address the ethical and regulatory issues that will be faced by any potential clinical trial of gene therapy during pregnancy.

RNAi and Gene Therapy: A Mutual Attraction

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 473-481 ◽  
Author(s):  
Dirk Grimm ◽  
Mark A. Kay
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Basic Research ◽  
Stem Cell Therapies ◽  
Adeno Associated Virus ◽  
Cell Therapies ◽  
Medical Benefits ◽  
Transfer Strategies ◽  
Delivery Vehicles ◽  
The Individual

AbstractThe phylogenetically conserved cellular phenomenon of RNA interference (RNAi)—the sequence-specific post-transcriptional silencing of gene expression mediated by small double-stranded RNAs—holds substantial promise for basic research and for drug development. Particularly attractive from a medical standpoint is the juxtaposition of new RNAi methodology with established gene transfer strategies, especially viral vectors for efficient and tissue-specific RNAi delivery to patients. Here, we summarize the latest experimental and clinical advances in RNAi-based gene therapy approaches. We briefly portray emerging nonviral strategies for siRNA transfer, before comparing the three viral vectors currently predominantly developed as shRNA delivery vehicles, adenovirus, lentivirus, and adeno-associated virus (AAV). Moreover, we describe the most clinically relevant genetic, acquired or infectious targets being pursued for therapeutic purposes. Specifically, we assess the use of vector-mediated RNAi for treatment of viral processes, solid cancers, lymphoproliferative disorders, and neurodegenerative and ocular diseases. In addition, we highlight further emerging applications, including stem cell therapies and animal transgenesis, as well as discuss some of the potential pitfalls and limitations inherent to the individual approaches. While we predict that eventual schemes will be shaped by our increasing understanding of the complexities of human RNAi biology, as well as by progressive refinements of viral shuttle designs, the potential scientific and medical benefits from a successful marriage of RNAi and gene therapy seem enormous.

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