Vaccinate yourself with TB vaccine to lead a pain-free life: TB/BCG vaccine-based activation of the PD-1 pathway for Pain therapy: TB/BCG vaccine, a tuberculosis vaccine,  increases the expression of PD-L1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 25/July/2018, 11.20 pm

Vasoactive intestinal polypeptide (VIP)-based therapy for blood sugar disease (autoimmune diabetes (TIDM)): Vasoactive intestinal polypeptide (VIP), a peptide hormone known to play a role in heart contractility, vasodilation, and blood pressure,  increases PD-L1 expression,  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, 24/July/2018,  10.24 pm
July 24, 2018
Unknown function of a known vaccine in the treatment of muscle atrophy and wasting: TB/BCG vaccine,  a tuberculosis vaccine,  increases the expression of FGF19 and its receptor ß-Klotho, phosphorylates ERK1/2 and S6K1, decreases the expression of tumor suppressors  genes, promotes regeneration of muscle cells and hypertrophy of skeletal muscle, and reverses muscular atrophy and wasting, via upregulation of its target gene, 25/July/2018, 11.49 pm
July 25, 2018
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 Introduction: What they say:

A recent study, from Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina, US, shows that “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.” This study was published, in the 22 May 2017 issue of Nature Neuroscience (one of the best journals in Neurobiology with an impact factor of 16.724+), by Prof Ji RR, Chen G, and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Vaccinate yourself with TB vaccine to lead a pain-free life (Is that so simple, let me test it out/begin a clinical trial): TB/BCG vaccine-based activation of the PD-1 pathway for Pain therapy: TB/BCG vaccine, a tuberculosis vaccine,  increases the expression of PD-L1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year. However, the work published recently, which is described below, may highlight the caveat in such an approach, as blocking PD-L1 may promote spontaneous pain and allodynia in cancer-bearing mice.

Prof. Ji has shown recently that: (1) Programmed cell death ligand-1 (PD-L1), produced by melanoma and normal neural tissues, inhibits acute and chronic pain; (2) injection of PD-L1 alleviates pain, and thereby functions as an analgesic agent; (3) Neutralization of PD-L1 or Block of PD1 promotes mechanical allodynia (hypersensitivity to pain); (4) PD1 null mice suffers from thermal and mechanical hypersensitivity; (5) PD-L1 promotes phosphorylation of SHP-1 and inhibits Sodium channels via PD-1 activation; and (6) PD-L1 inhibits nociceptive neuron excitability in dorsal root ganglion and thereby functions as a neuromodulator, suggesting that increasing the expression or the level of PD-L1/PD1 may alleviate pain and thermal and mechanical hypersensitivity.


From research findings to therapeutic opportunity:

This study suggests, first the first time, a Bacillus Calmette Guerin (BCG) vaccine-based regenerative therapy, with detailed mechanistic insights, for acute and chronic pain. BCG vaccine has been found to be useful in the treatment of tuberculosis, for more than 100 years, more recently in the treatment of autoimmune diabetes. However, the mechanism of action remains largely unknown.

TB/BCG vaccine, by increasing the expression of its target genes, it may increase PD-L1 levels (figs. 1-2). Thereby, it may: (a) inhibit acute and chronic pain; (b) alleviate thermal and mechanical hypersensitivity; (c) activate signal transduction cascade downstream of PD-1 receptor; (c) phosphorylate SHP-1; (d) inhibit sodium channels and nociceptive neuron excitability.

Figure 1.Mechanistic insights into how TB/BCG vaccine inhibits acute and chronic pain. TB/BCG vaccine enhances PD-L1 levels, suppresses thermal and mechanical hypersensitivity, phosphorylates SHP-1, inhibits activation of sodium channels, and alleviates nociceptive neuron excitability

Figure 2.Repurposing the TB/BCG vaccine into an analgesic vaccine. TB/BCG vaccine attenuates pain through induction of PDL1.

Thus, TB/BCG vaccine, either alone in combination with other drugs,” may be used to attenuate short-term and long-term pain.

Given the mechanistic insights as to how TB/BCG vaccine may function as an analgesic agent,  physicians may consider: vaccinating their needy patients with  TB/BCG vaccine or beginning a clinical trial. 

 

 

 

 

 

 


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $500#

Undisclosed mechanistic information: How TB/BCG vaccine increases the expression of PD-L1

# Research cooperation


References:

Citation: Boominathan, L., Vaccinate yourself with TB vaccine to lead a pain-free life: TB/BCG vaccine-based activation of the PD-1 pathway for Pain therapy: TB/BCG vaccine, a tuberculosis vaccine,  increases the expression of PD-L1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 25/July/2018, 11.20 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

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