STATUS AND POTENTIAL OF GENE THERAPY IN CLINICAL MEDICINE

2002 ◽  
Vol 18 (3) ◽  
pp. 645-674 ◽  
Author(s):  
Anita Lyngstadaas
Keyword(s):  
Gene Therapy ◽  
Clinical Research ◽  
Clinical Medicine ◽  
Severe Combined Immunodeficiency ◽  
Molecular Medicine ◽  
Phase Iii ◽  
Somatic Therapy ◽  
Health Authorities ◽  
Three Phase ◽  
Somatic Gene

Objective: Somatic gene therapy is a new method in the rapidly expanding field of molecular medicine. Due to recent encouraging results and the promising prospect for some disease groups, Norwegian health authorities wanted to assess somatic therapy with evidence-based standards for strategic use. This article presents the results of this assessment, discussed in the context of the policy-making process in Norway, including ethical and legislational considerations.Methods: Clinical gene therapy protocols, ongoing or completed with published results, where available, were identified through a systematic survey of descriptive protocols and publications. Preclinical literature was also reviewed.Results: Gene therapy is dominated by preclinical and clinical research. Most of the gene therapy protocols identified are in early phases (phases I and II) with only a few patients in each study. Of the protocols included in the assessment, only three phase III studies are represented. Except for the use of soluble antisense oligonucleotides against cytomegalovirus eye infection, gene therapy is presently not an established treatment modality. Promising results have been observed in treatment of cancer and cardiovascular diseases and, most recently, in inherited severe combined immunodeficiency and hemophilia. Several interesting principles addressing a large panel of conditions are currently being developed and tested.Conclusions: Gene therapy is developing into an important medical concept that needs to be included within the Norwegian healthcare system. It is recommended that the Norwegian Ministry of Health and Social Affairs fund a national program to boost infrastructure in selected scientific groups both in preclinical and clinical research. The national procedures regulating approval of gene therapy trials should be made more efficient while at the same time allowing for proper control and ethical considerations. It is emphasized that gene therapy trials should be carefully monitored for side effects.

Designing an eHealth Breastfeeding Resource With Young Mothers Using a Participatory Design

2020 ◽  
pp. 104365962095706
Author(s):  
Jennifer Abbass-Dick ◽  
Barbara Chyzzy ◽  
Amber Newport ◽  
Joanne Huizinga ◽  
Fangli Xie
Keyword(s):  
Health Care Providers ◽  
Participatory Design ◽  
Participatory Approach ◽  
Phase Iii ◽  
Learning Needs ◽  
Young Mothers ◽  
Care Providers ◽  
Breastfeeding Support ◽  
Health Authorities ◽  
Three Phase

Introduction Breastfeeding rates among young mothers are low and do not meet recommendations from health authorities, putting the health of young mothers and their infants at risk. Young mothers require breastfeeding support that meets their learning needs and preferred mode for accessing information. The objective of this study was to work collaboratively with young mothers in order to cocreate an eHealth breastfeeding resource. Methodology A three-phase exploratory study was conducted in Ontario, Canada. In Phases I and II, young mothers and health care providers (HCPs) were recruited and preferences for an eHealth breastfeeding resource were explored. In Phase III, feedback from young mothers and HCPs about the new resource was collected. Results Participants found the breastfeeding eHealth resource visually appealing, engaging, and informative. Discussion Cocreating a tailored breastfeeding eHealth resource with young mothers and HCPs using a participatory approach ensured that the resource design and content met the learning needs of young mothers.

Somatic Gene Therapy for X-Linked Severe Combined Immunodeficiency Using a Self-Inactivating Modified Gammaretroviral Vector Results in An Improved Preclinical Safety Profile and Early Clinical Efficacy in a Human Patient

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 164-164
Author(s):  
Sung-Yun Pai ◽  
Luigi Daniele Notarangelo ◽  
Chad Harris ◽  
Federica Cattaneo ◽  
Matthew Wladkowski ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Nk Cell ◽  
Severe Combined Immunodeficiency ◽  
Preclinical Studies ◽  
Human Patient ◽  
Fitness Score ◽  
Somatic Gene

Abstract Abstract 164FN2 Somatic gene therapy for X-linked severe combined immunodeficiency (X-SCID) using a MLV-based gammaretroviral vector expressing the IL-2 receptor gamma chain (MFG-γc) resulted in excellent immunologic reconstitution but also in insertional oncogenesis. In 5/20 treated children, T cell leukemia developed, with insertional activation of LMO2 proto-oncogene in 4 of the 5. We reasoned that replacing the virus-derived promoter and enhancer elements with a weaker cellular promoter would result in improved safety yet retain efficacy. We therefore generated the pSRS11.EFS.IL2RG.pre* self-inactivating (SIN) gammaretroviral vector in which expression of γc is controlled by an intronless EF1-α promoter, in a MLV vector devoid of the LTR U3 (enhancer/promoter) region. In preclinical studies we determined ‘relative safety' using several surrogate assays. In a reporter assay, the pSRS11.EFS.IL2RG.pre* vector when inserted into the oncogenic LMO2 locus induced LMO2 expression 6–90-fold less than the parent MFG vector (MFG-γc). pSRS11.EFS.IL2RG.pre* had lower activity in a murine in vitro immortalization assay (0.2 clones per 10e5 cells, fitness score 0.00007), compared to MFG-γc (0.54 clones per 10e5 cells, fitness score 0.00025). Peripheral blood and bone marrow from C57BL6 mice transplanted with murine bone marrow transduced with pSRS11.EFS.IL2RG.pre* and followed in primary recipients over 4 months and in secondary recipients over 1 year in vivo showed no evidence of vector associated leukemias. Deep sequencing demonstrated 8 of 3621 insertions into the MDS-associated gene Evi1 in mice transplanted with MFG-γc-transduced cells while there were none (0 of 2690 insertions into Evi1) in mice transplanted with pSRS11.EFS.IL2RG.pre* vector transduced cells (P=0.025). In preclinical efficacy studies, circulating T and B lymphocytes were detectable in the peripheral blood of 7/7 γc-deficient mice transplanted with pSRS11.EFS.IL2RG.pre* transduced cells while 4/4 mice repopulated with SFFV-eGFP transduced cells remained alymphoid. Experimental animals were sacrificed approximately five months post-transplant for analysis of immune reconstitution. Flow cytometric analysis of the spleens and bone marrow revealed restoration of mature B220+IgM+ B cells and NK cell populations in all mice transplanted with pSRS11.EFS.IL2RG.pre* transduced cells. CD4+ and CD8+ T cells were also detected in both tissues and in thymi recovered from transplanted animals. T cells in these mice proliferated in response to mitogenic stimuli. Immunoglobulin subclasses IgG1 and IgG2a detected in the plasma from pSRS11.EFS.IL2RG.pre* reconstituted mice also indicated restored B cell function in these animals. Human preclinical studies also supported the correction of XSCID cellular defects using this vector. Based on these data, a multi-institutional phase I/II trial was initiated with the pSRS11.EFS.IL2RG.pre* vector using an identical clinical protocol as in the previous X-SCID trials, to determine efficacy and safety compared with the MFG-γc vector. The first patient was treated in December 2010. Six months post-gene therapy, he has attained CD3 T cell count of >800, normal proliferation to mitogens, and normal NK cell numbers. He has cleared medically-resistant oral ulcers, and a rotavirus infection acquired post-gene therapy. Nearly all of the circulating T cells (86%) and 41% of his NK cells express γc, albeit at modestly lower density than normal, as expected. However, the early kinetics of T cell reconstitution was comparable to several subjects treated with MFG-γc. These data suggest that the improved safety profile demonstrated with numerous surrogate preclinical studies is associated with efficacious transgene expression and functional immune recovery in the initial human patient treated. Disclosures: Off Label Use: CliniMACS for selection of CD34+ hematopoietic cells. Baum:Patent office: Patents & Royalties.

Somatic Gene Therapy

1991 ◽  
Vol 5 (3) ◽  
pp. 423-432 ◽  
Author(s):  
Charles Hesdorffer ◽  
Dina Markowitz ◽  
Maureen Ward ◽  
Arthur Bank
Keyword(s):  
Gene Therapy ◽  
Somatic Gene Therapy ◽  
Somatic Gene

Correction of the Growth Defect in Dwarf Mice with Nonautologous Microencapsulated Myoblasts—An Alternate Approach to Somatic Gene Therapy

1995 ◽  
Vol 6 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Ayman Al-Hendy ◽  
Gonzalo Hortelano ◽  
Gloria S. Tannenbaum ◽  
Patricia L. Chang
Keyword(s):  
Gene Therapy ◽  
Growth Defect ◽  
Somatic Gene Therapy ◽  
Somatic Gene ◽  
Dwarf Mice

scholarly journals Exploring new uses for existing drugs: innovative mechanisms to fund independent clinical research

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ciska Verbaanderd ◽  
Ilse Rooman ◽  
Isabelle Huys
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Financial Support ◽  
Social Impact ◽  
Grey Literature ◽  
Economic Incentives ◽  
Phase Iii ◽  
Medical Needs ◽  
The Future ◽  
Funding Mechanisms

Abstract Background Finding new therapeutic uses for existing medicines could lead to safe, affordable and timely new treatment options for patients with high medical needs. However, due to a lack of economic incentives, pharmaceutical developers are rarely interested to invest in research with approved medicines, especially when they are out of basic patent or regulatory protection. Consequently, potential new uses for these medicines are mainly studied in independent clinical trials initiated and led by researchers from academia, research institutes, or collaborative groups. Yet, additional financial support is needed to conduct expensive phase III clinical trials to confirm the results from exploratory research. Methods In this study, scientific and grey literature was searched to identify and evaluate new mechanisms for funding clinical trials with repurposed medicines. Semi-structured interviews were conducted with 16 European stakeholders with expertise in clinical research, funding mechanisms and/or drug repurposing between November 2018 and February 2019 to consider the future perspectives of applying new funding mechanisms. Results Traditional grant funding awarded by government and philanthropic organisations or companies is well known and widely implemented in all research fields. In contrast, only little research has focused on the application potential of newer mechanisms to fund independent clinical research, such as social impact bonds, crowdfunding or public-private partnerships. Interviewees stated that there is a substantial need for additional financial support in health research, especially in areas where there is limited commercial interest. However, the implementation of new funding mechanisms is facing several practical and financial challenges, such as a lack of expertise and guidelines, high transaction costs and difficulties to measure health outcomes. Furthermore, interviewees highlighted the need for increased collaboration and centralisation at a European and international level to make clinical research more efficient and reduce the need for additional funding. Conclusions New funding mechanisms to support clinical research may become more important in the future but the unresolved issues identified in the current study warrant further exploration.

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