Introduction: What they say
A study from the International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, “L. Sacco” Department of Biomedical and Clinical Sciences, University of Milan, Milan 20157, Italy; and Nephrology Division, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA shows that “PD-L1 genetic overexpression or pharmacological restoration in hematopoietic stem and progenitor cells reverses autoimmune diabetes.” This research paper was published, in the 15 November 2017 issue of the journal “Science Translational Medicine” [One of the best research journals in Science with an I.F of 15 plus], by Prof. Fiorina P and Nasr MB and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:Vaccine-based curative therapy for autoimmune (Type I) diabetes (TIDM): Rotavirus vaccinepromotes the expression of PD-L1, attenuates the expression of tumor suppressor TXNIP, augments Tregs function, promotes immune tolerance, increases pancreatic β-cell proliferation and regeneration, increases insulin secretion, improves insulin sensitivity, increases energy utilization, and reverses TIDM, via up regulation of its target gene
From significance of the study to public health relevance:
Given that: (1) more than 422 million people worldwide are affected by Diabetes mellitus (DM); (2) Type 1 Diabetes (T1DM) constitutes about 5-10% (11 to 12 million) of all diabetic cases; (3) the incidence of T1DM is exponentially increasing year after year by 3%; (4) Type I diabetic patients need to inject insulin, for life long; (5) Diabetes is going to be one of the top 10 causes of death by 2030; (6) the life-long painful injection/drug treatment is required to treat DM; (7) the global economic cost spent for diabetes treatment in 2014 was little more than 600 billion US dollars, while treatment for T1DM costs about $15 billion dollars per annum, there is an urgent need to find: (i) a way to induce regeneration of adult ß-cells that were lost in DM;(ii) a side-effect-free natural product-based drug that does not harm or deplete adult stem cells; and (iii) a way to cure, not just treat, diabetes.
What is known?
Prof. Fiorina’s research team has recently shown that:(1) programmed death ligand 1 (PD-L1), the immune checkpoint regulator, is expressed poorly in hematopoietic stem and progenitor cells (HSPCs) of Type-1 diabetic (T1D) patients; (2) PD-L1 inhibits activated T-cells and thereby promotes immune tolerance; (3) the expression of PD-L1 is controlled by a network of miRNAs; (4) attenuating the expression of one of the miRNAs that target PD-L1 restores the expression of PD-L1 in HSPCs; (5) increasing the expression of PD-L1 in HSPCs, either genetically or pharmacologically, inhibits autoimmune response and reverses autoimmune diabetes; and (6) PD-L1 is expressed poorly in human HSPCs of T1D patients, suggesting that increasing the expression of PD-L1 in T1D patients may reverse and cure T1D.
From research findings to Therapeutic opportunity:
A recent study from the Walter and Eliza Hall Institute for Medical Research, University of Melbourne, Melbourne, Victoria, Australia; Murdoch Children’s Research Institute, Royal Children’s Hospital, School of Population and Global Health, University of Melbourne, Parkville, Victoria, Australia; and others shows that “Association of Rotavirus Vaccination With the Incidence of Type 1 Diabetes in Children.” This study was published, in the 22 January 2019 issue of the journal JAMA Pediatr. (“The journal’s Impact factor is 10.8, the highest-ranking pediatric journal in the world”), by Prof. Leonard C. Harrison MBBS, MD, DSc, FRACP, FRCPA, FAHMS, Kirsten P. Perrett MBBS, FRACP, PhD., and others. Although this study had pointed out the association of rotavirus vaccination with the lower incidence of Type 1 Diabetes in children, they did not come up the mechanism of action of Rotavirus vaccine as to how it prevents or protects against Type 1 Diabetes in Children.
This study presented here suggests, for the first time, with detailed mechanistic insights, that how Rotavirus vaccine prevents or protects against autoimmune (Type I) diabetes (TIDM).
Rotavirus vaccine, by increasing the expression of its target gene, it may increase the expression of PD-L1 , while decreasing the expression of tumor suppressor TXNIP. Thereby, it may: (1) increase Regulatory T-cells(Tregs) function; (2) decrease immune activation; (3) increase pancreatic-β-cell proliferation and regeneration; (4) increase expression of genes that promote insulin sensitivity and insulin secretion;(4) decrease metabolic stress; and (5) promote glucose homeostasis (Fig.1).Thus, Rotavirus vaccine can be used, either alone or in combination with other compounds or drugs, not only to vaccinate against rotavirus, but also to cure and protect against autoimmune (Type I) diabetes (TIDM) (Fig.2).
Given the detailed mechanistic basis as to how Rotavirus vaccine may decrease blood glucose levels; and aid in remission of or protect against or cure autoimmune (Type I) diabetes (TIDM), medical practitioners/diabetologists/gastroenterologists/Pediatricians may consider putting this promising finding into a larger clinical trial or adopt this as a mode of curative/remission/preventive therapy for Type I or autoimmune diabetes (Figs. 2-3).
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed information: How does Rotavirus vaccine increase the expression of PD-L1?
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Citation: Boominathan, L., Rotavirus Vaccine-based curative therapy for autoimmune (Type I) diabetes (TIDM): Rotavirus vaccine promotes the expression of PD-L1, attenuates the expression of tumor suppressor TXNIP, augments Tregs function, promotes immune tolerance, increases pancreatic β-cell proliferation and regeneration, increases insulin secretion, improves insulin sensitivity, increases energy utilization, and reverses TIDM, via up regulation of its target gene, 4/July/2019, 8.17 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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