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Key Points
To Do List
References
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- best options for treatment are:
- management with diet, rest, exercise, mind control
- genetic therapies - customized gene modifications tailored to the patient - only working to get to trials now
- steroids are only a temporary treatment ( not more than 14 days )
- biologics as defined now can create significant risks through immunity suppression
- surgery is challenging and is effective at best for 5 to 10 years at which point patient has larger problems with smaller digestive tract
- more
To Do List
References
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Key Concepts
Potential Value Opportunities
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Key Concepts
Genetic studies of Crohn's disease: Past, present and future - 2014
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075408/
The exact causes of Crohn's disease are unknown, though it is likely to involve a disrupted immunological response to gut microbiota in genetically susceptible individuals [2]. There is currently no known cure and disease is managed by a combination of immune-suppressing medications, dietary changes or surgery.
Potential Value Opportunities
Guide to Clinical Trials for Crohns
https://policylab.us/clinical-trials/crohns-disease/
start as assessment
This site finds local trials
List of trials within 100 miles of Mansfield
https://antidote.me/match/search/results/d3fa7cd5-c7cf-450e-bc81-b862cede9a87/1
Mayo Clinic Crohns Trials
https://www.mayo.edu/research/clinical-trials/diseases-conditions/crohn%27s-disease
Information on Crohns Clinical Trials in summary - not specific treatments
https://www.gastrojournal.org/article/S0016-5085(19)41240-7/fulltext
Other Stuff
Adjuvant Treatment of Crohn's Disease with Traditional Chinese Medicine: A Meta-Analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425422/
The meta-analysis indicated that treatment with Traditional Chinese Medicine ( TCM ) and Western Medicine (WM) was significantly superior compared to treatment with WM alone with regard to total effective rate, remission maintenance rate, reduction of C-reactive protein (CRP), reduction of erythrocyte sedimentation rate (ESR), clinical score reduction, and reduction of adverse events.
Using genes to triangulate the pathophysiology of granulomatous autoinflammatory disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281334/
how granulomas form in Crohns
Inflammatory granuloma formation
Unlike infectious granulomas, the impetus for inflammatory granuloma formation is unclear. In the prototypical granulomatous diseases of sarcoidosis and Crohn’s disease (CD), cytokine stimulation leads to macrophage migration into a site of inflammation (5, 6). These macrophages produce tumor necrosis factor α (TNF-α), which recruits additional macrophages and lymphocytes to the area (6). It is hypothesized that M1 (pro-inflammatory) macrophages, activated by Toll-like receptor (TLR) ligands and interferon (IFN)-γ produced by Th1 cells, predominate in the acute granulomatous process. Over time, the lesion undergoes tissue remodeling and becomes increasingly fibrotic, which is marked by a shift in macrophage polarity towards an M2 (remodeling/fibrosing) subtype (7, 8). Macrophages develop into epithelioid cells which eventually coalesce into multinucleated giant cells that secrete potent cytokines, including TNF-α, interleukin (IL)-1 and tumor growth factor-β (9, 10). These inflammatory factors attract CD4+ helper T cells, which help to further organize the granuloma. Th1 cells are particularly responsive to stimulation by IFN-γ and IL-12, and once recruited to the site of inflammation, they secrete IL-2 to stimulate T-cell proliferation, as well as additional IFN-γ which perpetuates macrophage activation and amplifies macrophage TNF-α secretion (6). As the granuloma matures, T-cell polarity shifts towards Th2 predominance, which is believed to contribute to increased fibrosis (9).
Taken together, these observations suggest that altered B-cell behavior may contribute to granuloma formation and granulomatous inflammation.
PLCγ2-associated antibody deficiency and immune dysregulation
PLAID is an autosomal dominant condition with a broad constellation of clinical and laboratory features (62). It is characterized universally by cold urticaria, together with antibody deficiency and immune dysregulation manifesting as susceptibility to recurrent infection, atopic disease, autoimmunity and cutaneous granulomatous inflammation. Many clinical features of PLAID correspond to abnormalities of specific immune cells that signal through PLCγ2, such as cold urticaria (mast cells), antibody deficiency (B cells), autoimmunity (NK and B cells) and susceptibility to infection (NK and B cells). Signaling abnormalities in macrophages and neutrophils may also contribute to the pathogenesis of granulomatosis in PLAID (63).
Potential Challenges
Crohn's disease study identifies genetic variant with potential to personalize treatment
https://www.sciencedaily.com/releases/2019/10/191007100427.htm
A genetic variant carried by 40% of the population explains why some patients develop antibodies against the anti-TNF drugs, infliximab and adalimumab and lose response. The authors conclude that a further trial is required to confirm that genetic testing prior to treatment will reduce the rate of treatment failure by facilitating the most effective choice of therapy for individual patients. The research is part of a program of work committed to finding the right drug for the right patient first time
Anti-tumour necrosis factor (TNF) drugs, infliximab and adalimumab, are used to treat patients with moderate to severe Crohn's disease and ulcerative colitis when other treatments have not worked. Also known as biological medicines, these drugs work by blocking TNF, a protein which drives persistent gut inflammation. Introduced in the 1990s, anti-TNF drugs now rank in the top five by drug spend in the NHS.
Candidate Solutions
2020 Crohns Information
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