Ethics of First-in-Human Transplantation Trials of Bioartificial Organs

2021 ◽  
Vol 66 (Special Issue) ◽  
pp. 62-63
Author(s):  
Dide de Jongh ◽  
◽  
Eline Bunnik ◽  
Emma Massey ◽  
◽  
...  
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Regenerative Medicine ◽  
Ethical Issues ◽  
Artificial Organs ◽  
Diabetic Patients ◽  
Bioartificial Organs ◽  
Deceased Donors ◽  
Cell And Gene Therapy

"The most effective treatment for type 1 diabetes is transplantation of either a whole pancreas from a deceased donor or islet cells derived from multiple deceased donors. However, transplantation has several limitations, including shortage of post-mortem donors and the need for post-transplant patients to use life-long immunosuppressive medication. In the last decade, the field of regenerative medicine has combined engineering and biological technologies in the attempt to regenerate organs. The European VANGUARD project aims to develop immune-protected bioartificial pancreases for transplantation into non-immunosuppressed type 1 diabetic patients. This project is creating a ‘combination product’ using cells and tissue from a variety of sources, including placentas and deceased donors. The clinical development of this complex product raises ethical questions for first-in-human (FIH) clinical trials. Under what conditions can bio-artificial organs safely are transplanted in humans for the first time? How can patients be selected, recruited and informed responsibly? In this presentation, we investigate the ethical conditions for clinical trials of bio-engineered organs, focusing inter alia on study design, subject selection, risk-benefit assessment, and informed consent. We present the results of a review of the literature on the ethics of clinical trials in regenerative medicine, cell and gene therapy and transplantation, and specify existing ethical guidance in the context of FIH transplantation trials of bioartificial organs. We conclude that this new and innovative area at the intersection of regenerative medicine, cell and gene therapy and transplantation requires adequate consideration of the ethical issues in order to guide responsible research and clinical implementation. "

scholarly journals Type 1 Diabetic Neuropathy and C-peptide

2004 ◽  
Vol 5 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Anders A. F. Sima ◽  
Weixian Zhang ◽  
George Grunberger
Keyword(s):  
Clinical Trials ◽  
Animal Studies ◽  
Large Scale ◽  
Structural Changes ◽  
Diabetic Complication ◽  
Diabetic Patients ◽  
C Peptide ◽  
Beneficial Effects ◽  
Regulatory Effects

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucoseindependent effects. Preclinical studies have demonstrated dose-dependent effects onNa+,K+-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.

Preparing for pivotal: solving challenges in scale for cell and gene therapy clinical trials

2021 ◽  
Vol 7 (7) ◽  
pp. 847-854
Author(s):  
Subbu Viswanathan ◽  
Richard Gaeto ◽  
Erin Goodhue Meyer ◽  
Chris Greenberg ◽  
Jim Wise
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Cell And Gene Therapy

scholarly journals Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2502
Author(s):  
Maki Watanabe ◽  
Yuya Nishikawaji ◽  
Hirotaka Kawakami ◽  
Ken-ichiro Kosai
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Regenerative Medicine ◽  
New Technologies ◽  
Recombinant Adenovirus ◽  
Methodological Principle ◽  
Therapeutic Effects ◽  
Patients With Cancer ◽  
Screening Study ◽  
Efficient Construction

Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse “CRAs that can specifically target tumors with multiple factors” (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.

Research on cell sources for brain cell replacement methods has gained major importance. Cell and gene therapy are potentially intriguing new domains of regenerative medicine

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Regenerative Medicine ◽  
Brain Cell ◽  
Brain Diseases ◽  
Host Immune System ◽  
Differentiation Potential ◽  
Cell Replacement ◽  
Cell Sources ◽  
Cell And Gene Therapy

Great advances in neurodegenerative disease, cell and gene therapy have been made in recent decades. Following the recent advancement of stem cell-based neuronal therapies, including managing their differentiation potential, research on cell sources for brain cell replacement methods has gained major importance. The objective is to obtain a certain neuronal cell fate to repair and restore the injured cell function. Several cell-based therapeutic techniques that show promise in animal HD models have failed to attain a similar degree of success in human patients. Despite its poor prospects, fetal transplantation has opened the door to a potentially intriguing new domain of regenerative medicine. However, many obstacles need to be overcome before pre-differentiated stem cells can be used in clinical trials, and, in particular, ensuring that the source of stem cells has optimal differentiation potential with full integration and functional enhancement, has measurable clinical benefits with minimal impact on the host immune system, and is tumor-free. New cell, molecular, and pharmacological approaches may assist enhance neuronal survival of transplanted cells, and consequently therapy for many fatal brain diseases. Molecular approaches, on the other hand, have looked into the idea of entirely eliminating HTT utilizing RNAi in the hopes of preventing the mutant protein that produced it in the first place. In contrast, HTT's physiological significance requires the application of procedures that specifically interfere with MHTHTT. The CRISPR/Cas9 approach gives researchers the ability to inactivate the mHTT allele by deleting or editing particular regions, leading to increased knowledge of how to prevent mutation-induced toxicity. Overall, despite their appealing ability to reverse mHTT-induced toxicity, these therapies may face difficulties due to the need to modify their design for individuals in order to ensure therapeutic safety.As clinical investigations are planned, genome editing already shows promise as a potent treatment to overcome clinical HD features. While there is no certainty that HD symptomatology can be fully eased, researchers must continue to hunt for ways to diminish it because it has such profound and life-threatening effects on patients and their families. These new treatments are supposed to bring a brighter future for HD sufferers.

scholarly journals Accelerating Innovation in the Creation of Biovalue

2017 ◽  
Vol 42 (5) ◽  
pp. 925-946 ◽  
Author(s):  
John Gardner ◽  
Andrew Webster
Keyword(s):  
Gene Therapy ◽  
Regenerative Medicine ◽  
Cell Therapy ◽  
Sociotechnical Imaginaries ◽  
The Creation ◽  
Cell And Gene Therapy

The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to “accelerate” innovation. This article examines in detail one such agency, the United Kingdom’s Cell and Gene Therapy Catapult (CGTC). We describe CGTC’s role as an accelerator agency and its value narrative, which combines both “health and wealth.” Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field.

TYPE 1 DIABETES MELLITUS, DIABETIC NEPHROPATHY: TRANSPLANTOLOGY POTENTIAL

2012 ◽  
Vol 67 (1) ◽  
pp. 54-60
Author(s):  
S. V. Got'e
Keyword(s):  
Type 1 Diabetes ◽  
Kidney Transplantation ◽  
Pancreas Transplantation ◽  
Research Work ◽  
Endocrine Function ◽  
Artificial Organs ◽  
Postoperative Treatment ◽  
Diabetic Patients ◽  
Surgical Technical

The review covers the role of transplantology in treatment of patients with type 1 diabetes and the state of its development in the world and in Russia. The results of major multicenter studies, devoted to the influence of simultaneous kidney and pancreas transplantation and kidney transplantation alone on life expectancy and quality of life of diabetic patients are summarized here. Experience in pancreas-kidney transplantation, gained in Academician V.I. Shumakov Federal Research Center of Transplantology and Artificial Organs, is described, including surgical technical and postoperative treatment. Also we perform the results of research work, devoted to the influence of pancreas transplantation on different homeostasis parameters, such as: oxidative stress parameters, homocysteine, receptor for advanced glycation endproduct (RAGE), and markers of endocrine function of pancreas transplant.

scholarly journals Preferences of Type 1 Diabetic Patients on Devices for Islet Transplantation

2020 ◽  
Vol 29 ◽  
pp. 096368972095234
Author(s):  
M. Rezaa Mohammadi ◽  
Farideh Dehkordi-Vakil ◽  
Joni Ricks-Oddie ◽  
Robert Mansfield ◽  
Himala Kashimiri ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Credit Card ◽  
Implantable Devices ◽  
Diabetic Patients ◽  
Type 1 Diabetic Patients ◽  
To Receive ◽  
Transplantation Site

Transplantation of pancreatic islets within a biomaterial device is currently under investigation in clinical trials for the treatment of patients with type 1 diabetes (T1D). Patients’ preferences on such implants could guide the designs of next-generation implantable devices; however, such information is not currently available. We surveyed the preferences of 482 patients with T1D on the size, shape, visibility, and transplantation site of islet containing implants. More than 83% of participants were willing to receive autologous stem cells, and there was no significant association between implant fabricated by one’s own stem cell with gender ( χ 2 (1, n = 468) = 0.28; P = 0.6) or with age ( χ 2 (4, n = 468) = 2.92; P = 0.6). Preferred location for islet transplantation within devices was under the skin (52.7%). 48.3% preferred microscopic disks, and 32.3% preferred a thin device (like a credit card). Moreover, 58.4% preferred the implant to be as small as possible, 25.4% did not care about visibility, and 16.2% preferred their implants not to be visible. Among female participants, 81% cared about the implant visibility, whereas this number was 64% for male respondents ( χ 2 test (1, n = 468) = 16.34; P < 0.0001). 22% of those younger than 50 years of age and 30% of those older than 50 did not care about the visibility of implant ( χ 2 test (4, n = 468) = 23.69; P < 0.0001). These results suggest that subcutaneous sites and micron-sized devices are preferred choices among patients with T1D who participated in our survey.

Ethical Preparedness and Performance of Gene Therapy Study Co-Ordinators

2008 ◽  
Vol 15 (2) ◽  
pp. 208-221 ◽  
Author(s):  
Gwen Anderson
Keyword(s):  
Gene Therapy ◽  
Clinical Trials ◽  
Ethical Issues ◽  
Research Integrity ◽  
Convenience Sample ◽  
Role Preparation ◽  
Perceived Preparedness ◽  
The Usa ◽  
And Performance

Little is known about study co-ordinators of gene therapy clinical trials. The purposes of this study were to: (1) describe characteristics of co-ordinators of gene therapy (transfer) clinical trials; (2) assess differences between nurse and non-nurse study co-ordinators; and (3) identify factors indicative of study co-ordinators' role preparation that could affect their role performance. This exploratory correlational study employed a convenience sample of 118 co-ordinators in the USA (55 participants; 47% response rate). The researcher created the Study Coordinator Role Preparedness and Performance Survey to assess factors or correlates of study co-ordinator performance. Analysis of variance was used to compare nurses and non-nurses, and men versus women on their perceived preparedness, perceived quality of orientation, and satisfaction with educational opportunities. The findings contribute to knowledge by identifying present inadequacies in the training of study co-ordinators and in recognizing the need for more effective provision of orientation and continuing education with respect to ethical issues, knowledge of genetic science, and potential research integrity challenges.

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