scholarly journals New Perspectives of Gene Therapy on Polyglutamine Spinocerebellar Ataxias: From Molecular Targets to Novel Nanovectors

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1018
Author(s):  
Fabiola V. Borbolla-Jiménez ◽  
María Luisa Del Prado-Audelo ◽  
Bulmaro Cisneros ◽  
Isaac H. Caballero-Florán ◽  
Gerardo Leyva-Gómez ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Trinucleotide Repeat ◽  
System Response ◽  
Spinocerebellar Ataxias ◽  
Molecular Tools ◽  
Protein Clearance ◽  
Immune System Response ◽  
Cellular Pathways ◽  
Therapy Strategies

Seven of the most frequent spinocerebellar ataxias (SCAs) are caused by a pathological expansion of a cytosine, adenine and guanine (CAG) trinucleotide repeat located in exonic regions of unrelated genes, which in turn leads to the synthesis of polyglutamine (polyQ) proteins. PolyQ proteins are prone to aggregate and form intracellular inclusions, which alter diverse cellular pathways, including transcriptional regulation, protein clearance, calcium homeostasis and apoptosis, ultimately leading to neurodegeneration. At present, treatment for SCAs is limited to symptomatic intervention, and there is no therapeutic approach to prevent or reverse disease progression. This review provides a compilation of the experimental advances obtained in cell-based and animal models toward the development of gene therapy strategies against polyQ SCAs, providing a discussion of their potential application in clinical trials. In the second part, we describe the promising potential of nanotechnology developments to treat polyQ SCA diseases. We describe, in detail, how the design of nanoparticle (NP) systems with different physicochemical and functionalization characteristics has been approached, in order to determine their ability to evade the immune system response and to enhance brain delivery of molecular tools. In the final part of this review, the imminent application of NP-based strategies in clinical trials for the treatment of polyQ SCA diseases is discussed.

scholarly journals Novel Vaccine Candidates against Tuberculosis

2020 ◽  
Vol 27 (31) ◽  
pp. 5095-5118 ◽  
Author(s):  
Zhihao Li ◽  
Changping Zheng ◽  
Marco Terreni ◽  
Lisa Tanzi ◽  
Matthieu Sollogoub ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Recent Progress ◽  
Multi Drug Resistance ◽  
System Response ◽  
Bacillus Calmette Guerin ◽  
Vaccine Research ◽  
Vaccine Candidates ◽  
Immune System Response ◽  
Extensively Drug Resistance

Ranking above AIDS, Tuberculosis (TB) is the ninth leading cause of death affecting and killing many individuals every year. Drugs’ efficacy is limited by a series of problems such as Multi- Drug Resistance (MDR) and Extensively-Drug Resistance (XDR). Meanwhile, the only licensed vaccine BCG (Bacillus Calmette-Guérin) existing for over 90 years is not effective enough. Consequently, it is essential to develop novel vaccines for TB prevention and immunotherapy. This paper provides an overall review of the TB prevalence, immune system response against TB and recent progress of TB vaccine research and development. Several vaccines in clinical trials are described as well as LAM-based candidates.

Enhancing Radiotherapy With Genetically Engineered Viruses

2007 ◽  
Vol 25 (26) ◽  
pp. 4090-4095 ◽  
Author(s):  
Sunil J. Advani ◽  
Ralph R. Weichselbaum ◽  
Steven J. Chmura
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Ionizing Radiation ◽  
Shuttle Vector ◽  
Genetically Engineered ◽  
Oncolytic Viruses ◽  
Genes Encoding ◽  
Survival Gene ◽  
Exogenous Genes ◽  
Therapy Strategies

Concurrent radiotherapy and chemotherapy have been used to treat a variety of tumors to improve local control and overall survival. Gene therapy strategies represent a novel means to further improve the therapeutic ratio of ionizing radiation. Cancer gene therapy strategies in clinical trials include the use of replication-defective shuttle vectors to deliver exogenous genes and replication-competent oncolytic viruses. This review focuses on these approaches in the context of radiotherapy and radiochemotherapy. In the shuttle vector approach, exogenous gene products that enhance ionizing radiation–mediated tumor cell destruction have been selected. Moreover, the expression of exogenous genes encoding therapeutic proteins can be regulated through the use of ionizing radiation–enhanced promoters. Also, genetically engineered attenuated replication-competent viruses have been investigated in clinical trials. Preclinical data indicate that ionizing radiation interacts with replication-competent oncolytic viruses to enhance viral replication and tumor destruction. Here, we review the background preclinical and current clinical data utilizing gene therapy with radiotherapy.

Therapies for RYR1-Related Myopathies: Where We Stand and the Perspectives

2021 ◽  
Vol 27 ◽  
Author(s):  
Mathilde Beaufils ◽  
Lauriane Travard ◽  
John Rendu ◽  
Isabelle Marty
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Rare Diseases ◽  
Clinical Assessment ◽  
Neuromuscular Diseases ◽  
Ryr1 Gene ◽  
Therapeutic Development ◽  
Therapy Strategies

: RyR1-related myopathies are a family of genetic neuromuscular diseases due to mutations in the RYR1 gene. No treatment exists for any of these myopathies today, which could change in the coming years with the growing number of studies dedicated to the pre-clinical assessment of various approaches, from pharmacological to gene therapy strategies, using the numerous models developed up to now. In addition, the first clinical trials for these rare diseases have just been completed or are being launched. We review the most recent results obtained for the treatment of RyR1-related myopathies, and, in view of the progress in therapeutic development for other myopathies, we discuss the possible future therapeutic perspectives for RyR1-related myopathies.

Hemophilia Gene Therapy: New Development from Bench to Bed Side

2019 ◽  
Vol 19 (4) ◽  
pp. 264-273 ◽  
Author(s):  
Xiao-Lu Guo ◽  
Tsai-Hua Chung ◽  
Yue Qin ◽  
Jie Zheng ◽  
Huyong Zheng ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Animal Models ◽  
Hemophilia A ◽  
Complete Cure ◽  
Genetic Tools ◽  
Inherited Diseases ◽  
New Development ◽  
Therapy Strategies ◽  
Genetic Strategies

Novel gene therapy strategies have changed the prognosis of many inherited diseases in recent years. New development in genetic tools and study models has brought us closer to a complete cure for hemophilia. This review will address the latest gene therapy research in hemophilia A and B including gene therapy tools, genetic strategies and animal models. It also summarizes the results of recent clinical trials. Potential solutions are discussed regarding the current barriers in gene therapy for hemophilia.

Towards More Successful Gene Therapy Clinical Trials for β-Thalassemia

2013 ◽  
Vol 13 (8) ◽  
pp. 1314-1330 ◽  
Author(s):  
E. Drakopoulou ◽  
E. Papanikolaou ◽  
M. Georgomanoli ◽  
N. Anagnou
Keyword(s):  
Gene Therapy ◽  
Clinical Trials

Gene Therapy Strategies in Prostate Cancer

2005 ◽  
Vol 5 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Iris Eder ◽  
Petra Haag ◽  
Georg Bartsch ◽  
Helmut Klocker
Keyword(s):  
Prostate Cancer ◽  
Gene Therapy ◽  
Therapy Strategies

scholarly journals Stem Cells and Gene Therapy in Progressive Hearing Loss: the State of the Art

2021 ◽  
Author(s):  
Aida Nourbakhsh ◽  
Brett M. Colbert ◽  
Eric Nisenbaum ◽  
Aziz El-Amraoui ◽  
Derek M. Dykxhoorn ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Hearing Loss ◽  
Treatment Modalities ◽  
Versus Gene ◽  
Vitro Model ◽  
New Treatment ◽  
Induced Pluripotent ◽  
Therapy Strategies

AbstractProgressive non-syndromic sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment, affecting more than a third of individuals over the age of 65. PNSHL includes noise-induced hearing loss (NIHL) and inherited forms of deafness, among which is delayed-onset autosomal dominant hearing loss (AD PNSHL). PNSHL is a prime candidate for genetic therapies due to the fact that PNSHL has been studied extensively, and there is a potentially wide window between identification of the disorder and the onset of hearing loss. Several gene therapy strategies exist that show potential for targeting PNSHL, including viral and non-viral approaches, and gene editing versus gene-modulating approaches. To fully explore the potential of these therapy strategies, a faithful in vitro model of the human inner ear is needed. Such models may come from induced pluripotent stem cells (iPSCs). The development of new treatment modalities by combining iPSC modeling with novel and innovative gene therapy approaches will pave the way for future applications leading to improved quality of life for many affected individuals and their families.

scholarly journals NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii124-ii124
Author(s):  
Jan Remsik ◽  
Xinran Tong ◽  
Ugur Sener ◽  
Danille Isakov ◽  
Yudan Chi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Leptomeningeal Metastasis ◽  
System Response ◽  
Idle State ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Immune System Response ◽  
Therapeutic Protocols ◽  
Brain And Spinal Cord

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.

scholarly journals Gene therapy strategies for idiopathic pulmonary fibrosis: recent advances, current challenges, and future directions

2021 ◽  
Vol 20 ◽  
pp. 483-496
Author(s):  
Mitchel J.R. Ruigrok ◽  
Henderik W. Frijlink ◽  
Barbro N. Melgert ◽  
Peter Olinga ◽  
Wouter L.J. Hinrichs
Keyword(s):  
Gene Therapy ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Future Directions ◽  
Recent Advances ◽  
Therapy Strategies

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

2019 ◽  
Vol 24 (3) ◽  
pp. 147-152 ◽  
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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