scholarly journals A few ethical issues in translational research for gene and cell therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Luciana Riva ◽  
Carlo Petrini
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Translational Research ◽  
Early Phase ◽  
Ethical Issues ◽  
The United States ◽  
Cell Therapies ◽  
Biomedical Technologies ◽  
Regulatory Approach ◽  
Gene And Cell Therapy

Abstract Background Although translational research for drug development can provide patients with valuable therapeutic resources it is not without risk, especially in the early-phase trials that present the highest degree of uncertainty. With the extraordinary evolution of biomedical technologies, a growing number of innovative products based on human cells and gene therapy are being tested and used as drugs. Their use on humans poses several challenges. Methods In this work, we discuss some ethical issues related to gene and cell therapies translational research. We focus on early-phase studies analysing the regulatory approach of Europe and the United States. We report the current recommendations and guidelines of international scientific societies and European and American regulatory authorities. Results The peculiarity of human cell- or tissue-based products and gene therapy has required the development of specific regulatory tools that must be continually updated in line with the progress of the research. The ethics of translational research for these products also requires further considerations, particularly with respect to the specificity of the associated risk profiles. Conclusions An integrated ethical approach that aims for transparency and regulation of development processes, the support of independent judgment in clinical trials and the elimination of unregulated and uncontrolled grey areas of action are necessary to move gene and cell therapy forward.

scholarly journals Equitable Access to Gene Therapy: A Call to Action for the American Society of Gene and Cell Therapy

2018 ◽  
Vol 26 (12) ◽  
pp. 2715-2716 ◽  
Author(s):  
Kenneth Cornetta ◽  
Kirtika Patel ◽  
Christopher Mwaniki Wanjiku ◽  
Naftali Busakhala
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Equitable Access ◽  
Call To Action ◽  
American Society ◽  
Gene And Cell Therapy

scholarly journals Understanding and Prevention of “Therapy-” Induced Dyskinesias

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Iciar Aviles-Olmos ◽  
Zinovia Kefalopoulou ◽  
Thomas Foltynie
Keyword(s):  
Gene Therapy ◽  
Synaptic Plasticity ◽  
Basal Ganglia ◽  
Cell Therapy ◽  
Dopamine Release ◽  
The Subject ◽  
Cell And Gene Therapy ◽  
Further Development ◽  
Gene And Cell Therapy

L-dopa is the most effective, currently available treatment for Parkinson’s disease (PD), but it leads to the development of involuntary movements known as L-dopa-induced dyskinesia (LID) in the majority of patients after long-term use. Both gene and cell therapy approaches are the subject of multiple ongoing studies as potential ways of relieving symptoms of PD without the complication of dyskinesia. However, the spectre of dyskinesia in the absence of L-dopa, the so-called “off-phase” or graft-induced dyskinesia (GID), remains a major obstacle particularly in the further development of cell therapy in PD, but it is also a concern for proponents of gene therapy approaches. LID results from nonphysiological dopamine release, supersensitivity of dopamine receptors, and consequent abnormal signalling through mechanisms of synaptic plasticity. Restoration of physiological circuitry within the basal ganglia loops is ultimately the aim of all cell and gene therapy approaches but each using distinctive strategies and accompanied by risks of exacerbation of LID or development of “off-phase”/GID. In this paper we discuss the details of what is understood regarding the development of dyskinesias with relevance to cell and gene therapy and potential strategies to minimize their occurrence.

Stem Cell Smart Technology, where are we now and how far we have to go?

Vascular ◽  
2017 ◽  
Vol 26 (2) ◽  
pp. 216-228
Author(s):  
Sherif Sultan ◽  
Edel P Kavanagh ◽  
Robert Michalus ◽  
Niamh Hynes
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Clinical Results ◽  
Arterial Disease ◽  
The United States ◽  
Stem Cell Technology ◽  
Smart System ◽  
Cell Therapies ◽  
Peripheral Arterial ◽  
Contemporary Practice

Approximately eight million people in the United States have peripheral arterial disease, which increases exponentially with age. There have been a plethora of available treatments including surgery, angioplasty, atherectomy, laser technology, and cell-based therapies. Cell-based therapies were developed in the hope of translating laboratory-based technology into clinical successes. However, clinical results have been disappointing. Infusion or injection for stem cell therapy is still considered experimental and investigational, and major questions on safety and durability have arisen. In no option patients, how can they be treated safely and successfully? In this article, we review contemporary practice for cell therapy, its pitfalls and breakthroughs, and look at the future ahead. We introduce a novel smart system for minimally invasive delivery of cell therapies, which exemplifies the next generation of endovascular solutions to stem cell technology and promises safety, efficacy, and reliability.

scholarly journals Autologous Gene and Cell Therapy Provides Safe and Long-Term Curative Therapy in A Large Pig Model of Hereditary Tyrosinemia Type 1

2018 ◽  
Vol 28 (1) ◽  
pp. 79-88 ◽  
Author(s):  
Raymond D. Hickey ◽  
Clara T. Nicolas ◽  
Kari Allen ◽  
Shennen Mao ◽  
Faysal Elgilani ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Ex Vivo ◽  
Curative Therapy ◽  
Ex Vivo Gene Therapy ◽  
Tyrosinemia Type 1 ◽  
Hereditary Tyrosinemia ◽  
Gene And Cell Therapy

Orthotopic liver transplantation remains the only curative therapy for inborn errors of metabolism. Given the tremendous success for primary immunodeficiencies using ex-vivo gene therapy with lentiviral vectors, there is great interest in developing similar curative therapies for metabolic liver diseases. We have previously generated a pig model of hereditary tyrosinemia type 1 (HT1), an autosomal recessive disorder caused by deficiency of fumarylacetoacetate hydrolase (FAH). Using this model, we have demonstrated curative ex-vivo gene and cell therapy using a lentiviral vector to express FAH in autologous hepatocytes. To further evaluate the long-term clinical outcomes of this therapeutic approach, we continued to monitor one of these pigs over the course of three years. The animal continued to thrive off the protective drug NTBC, gaining weight appropriately, and maintaining sexual fecundity for the course of his life. The animal was euthanized 31 months after transplantation to perform a thorough biochemical and histological analysis. Biochemically, liver enzymes and alpha-fetoprotein levels remained normal and abhorrent metabolites specific to HT1 remained corrected. Liver histology showed no evidence of tumorigenicity and Masson’s trichrome staining revealed minimal fibrosis and no evidence of cirrhosis. FAH-immunohistochemistry revealed complete repopulation of the liver by transplanted FAH-positive cells. A complete histopathological report on other organs, including kidney, revealed no abnormalities. This study is the first to demonstrate long-term safety and efficacy of hepatocyte-directed gene therapy in a large animal model. We conclude that hepatocyte-directed ex-vivo gene therapy is a rational choice for further exploration as an alternative therapeutic approach to whole organ transplantation for metabolic liver disease, including HT1.

scholarly journals Clinical Translation of Cell Therapies in Stroke (CT2S) Checklist—a pragmatic tool to accelerate development of cell therapy products

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anjali Nagpal ◽  
Austin G. Milton ◽  
Simon A. Koblar ◽  
M. Anne Hamilton-Bruce
Keyword(s):  
Health Economic ◽  
Cell Therapy ◽  
Study Design ◽  
Early Phase ◽  
Research Output ◽  
Phase Cell ◽  
Cell Therapies ◽  
Stroke Research ◽  
Data Elements ◽  
The Impact

Abstract Background Cell therapies present an exciting potential but there is a long history of expensive translational failures in stroke research. Researchers engaged in cell therapy research would benefit from a practical framework that can help in planning research and development of investigational cell therapies into viable medical products. Methods We developed a checklist using a mixed methodology approach to evaluate the impact of study design, regulatory policy, ethical, and health economic considerations for efficient implementation of early phase cell therapy studies. Results The checklist comprises a series of questions arranged under four domains: the first concerns study design such as characterization of target study population, trial design, endpoints and operational fit of dosage, time, and route of administration to target populations. A second domain addresses the data package required for regulatory approval relevant to the intended use (allogeneic/autologous; homologous/non-homologous; nature of cell processing). The third domain comprises patient involvement to ensure relevant data is collected via targeted study design. The final domain requires the team to determine the critical data elements that could be built into study design to enable health economic data collection to be started at an early phase of the study. Conclusions The CT2S checklist can help to determine areas of expertise gaps and enable research groups to appropriately allocate resources for capacity building. Use of this checklist will allow identification of key areas where trial planning needs to be optimized, as well as helping to identify resources that need to be secured. The CT2S checklist can also serve as a general cell therapy research decision aid to improve research output and accelerate new cell therapy development.

The European Society of Gene and Cell Therapy: A Nearly 30-Year Endeavor to Make Gene Therapy a Clinical Reality

2021 ◽  
Vol 32 (19-20) ◽  
pp. 979-982
Author(s):  
Hildegard Büning ◽  
Elizabeth Wilson ◽  
Juan Bueren ◽  
Axel Schambach ◽  
Alberto Auricchio
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
European Society ◽  
Clinical Reality ◽  
Gene And Cell Therapy

scholarly journals Maximizing the Survival of Amyotrophic Lateral Sclerosis Patients: Current Perspectives

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Osama A. Khairoalsindi ◽  
Ahmad R. Abuzinadah
Keyword(s):  
Gene Therapy ◽  
Amyotrophic Lateral Sclerosis ◽  
Stem Cell ◽  
Cell Therapy ◽  
Motor Neurons ◽  
Stem Cell Therapy ◽  
The United States ◽  
Disease Modifying Drugs ◽  
Familial Form ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis is a neurodegenerative disease that leads to loss of the upper and lower motor neurons. Almost 90% of all cases occur in the sporadic form, with the rest occurring in the familial form. The disease has a poor prognosis, with only two disease-modifying drugs approved by the United States Food and Drug Administration (FDA). The approved drugs for the disease have very limited survival benefits. Edaravone is a new FDA-approved medication that may slow the disease progression by 33% in a selected subgroup of ALS patients. This paper covers the various interventions that may provide survival benefits, such as early diagnosis, medications, gene therapy, stem cell therapy, diet, nutritional supplements, multidisciplinary clinics, and mechanical invasive and noninvasive ventilation. The recent data on masitinib, the role of enteral feeding, gene therapy, and stem cell therapy is discussed.

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