Tackling autoimmunity with gene therapy

Alderuccio, Frank; Toh, Ban‐Hock

doi:10.4161/chim.22061

Cited by 2 publications

(3 citation statements)

References 20 publications

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“…Understanding and then correcting this imbalance may greatly contribute to our health and well-being. Notably, at least in animal model, autoimmunity can be tackled by gene transfer to promote immune tolerance ( 181 , 182 ). We hope that the hypothesis proposed here will encourage the medical and scientific communities to evaluate the risks associated with HGT events in the human gut.…”

Section: Discussionmentioning

confidence: 99%

Potential Effects of Horizontal Gene Exchange in the Human Gut

Tenbusch²,

2017

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Many essential functions of the human body are dependent on the symbiotic microbiota, which is present at especially high numbers and diversity in the gut. This intricate host–microbe relationship is a result of the long-term coevolution between the two. While the inheritance of mutational changes in the host evolution is almost exclusively vertical, the main mechanism of bacterial evolution is horizontal gene exchange. The gut conditions, with stable temperature, continuous food supply, constant physicochemical conditions, extremely high concentration of microbial cells and phages, and plenty of opportunities for conjugation on the surfaces of food particles and host tissues, represent one of the most favorable ecological niches for horizontal gene exchange. Thus, the gut microbial system genetically is very dynamic and capable of rapid response, at the genetic level, to selection, for example, by antibiotics. There are many other factors to which the microbiota may dynamically respond including lifestyle, therapy, diet, refined food, food additives, consumption of pre- and probiotics, and many others. The impact of the changing selective pressures on gut microbiota, however, is poorly understood. Presumably, the gut microbiome responds to these changes by genetic restructuring of gut populations, driven mainly via horizontal gene exchange. Thus, our main goal is to reveal the role played by horizontal gene exchange in the changing landscape of the gastrointestinal microbiome and potential effect of these changes on human health in general and autoimmune diseases in particular.

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Section: Discussionmentioning

confidence: 99%

Potential Effects of Horizontal Gene Exchange in the Human Gut

Tenbusch²,

2017

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“…Another contribution of the mouse model of EAE is that it has demonstrated that non-myeloablative and less toxic conditioning generates autoantigen-encoding bone marrow that promotes tolerance, with low levels of chimerism. Besides, it prevents relapses and also reverses established disease [11,12]. …”

Section: Peripheral Immunity and Cns Pathologymentioning

confidence: 99%

“…Furthermore, AHSCT could include the use of genetically modified autologous hematopoietic stem cells in the future [7]. By means of genetically modified AHSCT it would be possible to promote immune tolerance toward antigens or a wide variety of molecules, thus permitting the identification and elimination of pathogenic cellular clones or the creation of lymphocytes capable of controlling and suppressing the activity of self-reactive clones [12]. Recent studies in animal models using mesenchymal stem cells transplant or induced pluripotent stem cell (iPSCs) derived precursor cells have shown both neurogenesis, and a therapeutic effect as modifiers of the immune response and promoters of regeneration in CNS diseases including MS [46–48].…”

Section: Biomarkersmentioning

confidence: 99%

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up

Londoño

Mora

2016

J Clin Cell Immunol

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BackgroundDespite the current availability of disease modifying therapies for the treatment of multiple sclerosis, there are still patients who suffer from severe neurological dysfunction in the relapsing-remitting or early progressive forms of the disease. For these patients autologous hematopoietic stem cell transplant offers an important therapeutic solution to prevent progression to irreversible disability. In spite of multiple studies in the last two decades, patient inclusion criteria, protocols for peripheral blood stem cell mobilization and bone marrow cell conditioning and methodology of follow up for autologous hematopoietic stem cell transplant in multiple sclerosis have not been strictly unified.MethodsWe reviewed five recent clinical studies that confirmed the positive outcome of transplant in spite of disclosing significant differences in methodology of enrollment including patient disease subtypes, disease duration range, disability, regimens of peripheral blood stem cell mobilization and bone marrow cell conditioning, scheduling of imaging studies after transplant, and absence of laboratory biomarkers consistently applied to these studies.ResultsTherapy with autologous hematopoietic stem cell transplant has shown best results among young individuals with severe relapsing-remitting or early progressive disease through its ability to maintain no evidence of disease activity status in a significantly higher proportion of patients after transplant in comparison to patients treated with disease modifying therapies. Important cross-sectional differences in the reviewed studies were found.ConclusionA specific and careful selection of biomarkers, based on the current physiopathological mechanisms known to result in multiple sclerosis, will contribute to a better and earlier patient selection for autologous hematopoietic stem cell transplant and follow up process. An objective and measurable response could be obtained with the determination of biomarkers at the onset of treatment and after follow-up on reconstitution of the immune response. The application of such parameters could also help further our understanding of pathogenesis of the disease.

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Tackling autoimmunity with gene therapy

Cited by 2 publications

References 20 publications

Potential Effects of Horizontal Gene Exchange in the Human Gut

Potential Effects of Horizontal Gene Exchange in the Human Gut

Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up

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