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Posted 10/8/2017 6:38 PM (GMT -7)
www.crohnsforum.com/showthread.php?t=82362
Posted 10/9/2017 2:08 PM (GMT -7)
Looks like some interesting reading - thanks for sharing.
Posted 12/28/2017 9:02 PM (GMT -7)
The support group is expanding, if anyone is interested.
Posted 12/29/2017 9:50 AM (GMT -7)
Thank you for this!

Connor: how are you doing on it ?
Posted 12/30/2017 12:10 AM (GMT -7)
You're welcome.
Posted 7/7/2018 7:12 PM (GMT -7)

The report said...
top-line results from the study are expected to be announced in the coming weeks.

The report said...
If the MAP US study results are positive, RedHill will meet with key opinion leaders and the U.S. Food and Drug Administration (FDA) to present the data package and discuss the preferred path to potential approval.

/globenewswire.com/news-release/2018/07/02/1532291/0/en/RedHill-Biopharma-Announces-Allowance-of-Two-New-RHB-104-Patents-Ahead-of-Top-Line-Phase-III-Results-for-Crohn-s-Disease.html
Posted 7/10/2018 1:44 AM (GMT -7)
Finally, we will have a robust answer to the MAP problem, and possibly a new treatment option.
Posted 12/17/2018 3:15 AM (GMT -7)
Got scar tissue? This is interesting.

Anti-mycobacterial therapy in Crohn's disease heals mucosa with longitudinal scars
T.J.BorodyS.BilkeyA.R.WettsteinS.LeisG.PangS.Tye

Abstract
Background
A possible causative link between Crohn's disease and Mycobacterium avium ss paratuberculosis has been suggested.

Aim
To report unique scarring in Crohn's disease patients treated with anti-Mycobacterium avium ss paratuberculosis therapy.

Patients
A retrospective review of 52 patients with severe Crohn's disease was conducted. Thirty-nine patients who had at least one follow-up colonoscopy during treatment were included.

Methods
Patients received rifabutin (up to 600 mg/day), clofazimine (up to 100 mg/day) and clarithromycin (up to 1 g/day) – anti-Mycobacterium avium ss paratuberculosis therapy – for 6 months to 9 years. Ramp-up dosing was used. Colonoscopies and histological analyses monitored progress.

Results
Twenty-two patients (56.4%, 22/39) healed with unusual scarring, which appeared as branched, ribbon-like, elevated lines. In 2/6 patients (33.3%) who had >3 years of treatment after scarring occurred, scars receded, becoming imperceptible as full healing occurred. Histologically, a marked reduction in inflammation occurred in 15/39 patients (38.5%). Of these, 6/15 patients (40%) displayed restoration of normal mucosa. Longitudinal scarring occurred in 12/15 patients (80%) with improved histology.

Conclusions
The presence of scarring fading to normal mucosa on anti-MAP therapy implies a more profound healing not seen with standard anti-inflammatory and immunosuppressant drugs. Longitudinal scarring and consequent healing with normal histology should become a standard treatment goal for Crohn's disease.

https://www.sciencedirect.com/science/article/pii/s1590865807000138
Posted 12/17/2018 10:24 AM (GMT -7)
Far from a smoking gun, but more evidence (albeit from a very small sample, and from an author with a financial interest in a MAP drug) that anti-map antibiotic therapy might benefit CD patients.

Unfortunately, the very things that make MAP more plausible in the etiology and course of CD, make it even less clear that MAP has anything to do with UC. For example, they take the mutation on the NOD2 gene that raises the odds of CD by 20 to 40 percent as support for MAP because NOD2 has a "role in apoptosis and in the recognition of microbial endotoxins" - Unfortunately NOD2 mutations are not associated with change in risk for UC. That's not one of the genes CD and UC share.

The longitudinal analysis of scar tissue to that only seems to occur with anti-MAP is novel and interesting. The suggestion that mucosal healing is different with anti-inflammatory therapy versus antibacterial therapy, and may be "more complete" with antibacterial therapy, is promising for CD patients.

Ultimately some stem-cell therapy targeting the NOD2 mutation might be preferred because it is only a matter of time until drug-resistant MAP strains emerge that are resistant to the current triple-antibiotic cocktail being used. Also, since MAP is so common in the food chain, even after antibiotic treatment, ongoing treatment, or the development of a vaccine, is needed to prevent reinfection. Getting the NOD2 gene to work as intended would be the best ultimate therapy.

Both the number of genes and drugs the CD and UC have in common, as well as the growing areas (both genes and drugs) where they are different all go towards the kind of complete understandings that might herald in some UC progress too.
Posted 3/26/2019 8:34 AM (GMT -7)
The Crohn's MAP vaccine is being tested on healthy people now, and the trial on Crohn's patients will begin soon.

Article said...
Volunteers, mainly made up of Crohn’s patients and their families also raised £700,000 for a diagnostic blood test to run in conjunction with the vaccine trials. Fundraising is still taking place to take the trials to completion.

The website says: “Historically, MAP in humans has been difficult to study as it cannot be seen under an ordinary microscope and is very difficult to grow.

“Testing for MAP by the presence of its DNA (using PCR) has found MAP in up to 92% of Crohn’s patients but until now no-one has developed a test to show MAP in-situ in the tissues of people with Crohn’s disease.

“With the new MAP test developed by Professor Hermon-Taylor, we are seeing it in intricate detail for the very first time.

“The test is an essential ‘companion diagnostic’ for the Vaccine trial; a simple blood test allowing doctors to confirm MAP infection prior to vaccination and monitor patients’ responses to the vaccine. Validation of the new test is almost complete”.

Phase one trial of the second component of the vaccine is now underway on healthy volunteers and it is hoped phase two on Crohn’s patients will run in tandem, beginning at the end of April this year.

If all goes according to plan, trials should be completed by the middle of 2020.

The vaccine has garnered huge support on social media sites including Facebook, Twitter and Instagram.

To find out more, visit www.crohnsmapvaccine.com

https://www.edinburghnews.scotsman.com/news/health/vaccine-hope-to-treat-crohn-s-disease-is-one-step-closer-1-4890394


Info on entry criteria:

CMV Website said...

Can I be involved in the Vaccine trial? And when is the Vaccine likely to be available?

A phase I safety trial in healthy human volunteers began in March 2017. This will be followed by a Phase IIa trial, anticipated to begin in the first half of 2019. The Phase IIa trial will be a single-centre trial based at St. Thomas’s Hospital, London, UK in 20 adults with Crohn’s Disease and will last 1 year. The estimated timeline of the Vaccine manufacture and trials is shown in the Gantt Chart below. The patients recruited to this trial will need to meet strict entry criteria; there are stringent regulations which we have to obey and the trial will be governed by the close scrutiny of the regulators. Regrettably we cannot invite people to take part in the trial at this time. However, the results of the trial will be analysed in real time as it proceeds. As soon as there is evidence of safety and efficacy, we can apply for use of the vaccine on compassionate grounds; this will enable people who wish to have the vaccine but are unable to be part of the trial to access it on a named-patient basis outside of the trial. Indeed, under the newly proposed ‘Early Access to Medicines’ scheme in the UK, severely ill patients who have failed existing treatments may be granted access to new medicines that are proven to be safe, even before efficacy has been fully established. In addition, following the demonstration of safety and efficacy, it is anticipated that the Vaccine technology would be licenced to a pharmaceutical company to make it available to all who need it through health services worldwide -as part of this, larger Phase 3 trials inviting wider participation would be expected. The manufacture and trial of the Vaccine is being funded through investment in the company HAV Vaccines Ltd (HVL) -completion of the trial according to this timescale is dependent on HVL to secure the remainder of the funding required.

VIEW IMAGE

Timelines are current best estimates and are not set in stone. Delays are commonplace in research due to the unpredictable nature of organising and running trials (last updated 03.01.2019)

From: http://www.crohnsmapvaccine.com/faq/

Post Edited (xy123) : 3/26/2019 1:39:24 PM (GMT-6)

Posted 3/26/2019 12:56 PM (GMT -7)
More info on the phase I trial (on healthy volunteers):
https://www.jenner.ac.uk/hav001-vaccine-trial
https://www.jenner.ac.uk/_asset/file/hav001-vis-3-0.pdf


Crohn's MAP Vaccine March 2019 newsletter: https://mailchi.mp/crohnsmapvaccine/introducing-world-map-day-and-the-crohns-map-vaccine-cured-not-managed-shop-1740145?e=2f7cd0cabe
Posted 3/28/2019 5:11 PM (GMT -7)
do you think this might also work for uc?
Posted 3/29/2019 5:37 AM (GMT -7)
MAP has a near 100% presence in crohn's patients, but a lot smaller incidence in UC patients. Possible map might be a secondary, opportunistic infection in a smaller percentage of UC patients. So, some of us might benefit, but not a lot. Some of the studies point to a different non-MAP bacteria strain being near 100% common in UC patients (forget the name off of the top of my head) being the culprit with UC patients. So, if the MAP-Vaccine proves successful in Crohn's, they'll likely create a similar vaccine for the UC-problematic bacterium. As with everything, all new treatments are first developed and tried with Crohn's as it is deemed uncurable, whereas UC is curable via surgery.
Posted 3/29/2019 6:03 AM (GMT -7)
I thought I have read things recently that UC may be caused by a virus rather than a bacterium.... interestingly xeljanz seems to be a more potent immunosuppressant for viruses than bacteria, which could explain why it works better for colitis than crohns? (It still didn't pass clinical trials for crohns as far as I'm aware)
Posted 3/29/2019 7:30 AM (GMT -7)
It's all speculation. I always think the word cure isn't really what will happen, sometimes folks get a little over excited and jump before the evidence points toward that endpoint. More of a, novel treatment that might help some of us that have not found a solution through other currently available treatments.

We know our bacterium, viral, and fungus makeup in our guts is very weird compared to others. Normal folks have great diversity, high concentrations of good, and low concentrations of bad. We have high concentrations of bad ones (opportunists, and those that might aid inflammatory processes), low diversity, and low concentrations of good, etc.

Some of the MAP treatments is targeting one of the suspecting baddies. MAP is one heck of a smart bug, immune resistant, antibiotic resistant, and therefore is difficult for the immune system or conventional antibiotics to kill. I do not know a lot about the suspected UC-baddie being thought to be the UC culprit/target but I would expect it is similar in being pretty darn smart (thus it is a chronic problem for us). They could be wrong, the jury is still out.

Xeljanz, like most conventional UC treatments, interferes with part of the inflammatory processes our immune system normally follows. We feel better, less inflammation happens, etc. Xeljanz is a small molecule that works inside the interior of our body's cells. True biologics, like remicade/entyvio are very large molecules that work on only the outside of the cell walls; cannot enter cells.

Post Edited (iPoop) : 3/29/2019 8:36:17 AM (GMT-6)

Posted 5/29/2019 10:25 AM (GMT -7)
Jenner Institute published safety data for the Crohn's Map Vaccine.

http://www.crohnsmapvaccine.com/safety-immunogenicity-novel-recombinant-simian-adenovirus-chadox2-vectored-vaccine/

https://twitter.com/profkatieewer/status/1129010584979214336
Posted 5/29/2019 10:42 AM (GMT -7)
Relevant info:

3.2. Vaccine Safety

ChAdOx2 HAV was well tolerated at all dose groups. A total of 40 adverse events (AEs) considered possibly, probably or definitively related with the study vaccine were reported. Of those 15 (37.50%) were local and 25 (65.50%) were systemic AEs.
Local adverse reactions included pain, redness, itching, and warmth (Figure 2a). Injection site pain was the most common local AE experienced by 66.67% (39.06–86.19 95%CI) of the 12 volunteers vaccinated and were more common amongst volunteers receiving the higher dose (group 3) than amongst the participants in groups 1 and 2 (OR 10.0, 0.65–154.4 95%CI).
Headache and fatigue (50%, 25.38–74.62% 95%CI) were the most common systemic adverse reactions. Other systemic AEs reported included subjective feverishness, malaise, myalgia and arthralgia (Figure 2b and supplementary Table 1). A breakdown of adverse reactions by dose is provided in the supplementary material (supplementary figures S1–S6). Laboratory AEs are presented in supplementary Table 2.
There were no serious adverse reactions following vaccination with ChAdOx2 HAV, at any given dose. Neither objective fever nor severe AEs considered to be at least possibly related with the vaccine were reported.
The vast majority of AEs were mild in nature (85%, 70.93–92.94% 95%CI) and all were selflimited. Pain at injection site resolved within 4 days and all other AEs resolved within 24–72 hours.
Posted 5/31/2019 6:50 AM (GMT -7)
Anti-MAP therapy for Crohn's disease - Guy's and St Thomas' NHS ...

https://www.guysandstthomas.nhs.uk/resources/patient-information/gi/anti-map-therapy-for-crohns.pdf
Posted 5/31/2019 6:52 AM (GMT -7)
P550 Anti-mycobacterium paratuberculous therapy in Crohn’s disease: outcomes from tertiary IBD referral centres
E Johnston S Honap B Al-Hakim J Sanderson

Journal of Crohn's and Colitis, Volume 13, Issue Supplement_1, March 2019, Page S389, https://doi.org/10.1093/ecco-jcc/jjy222.674
Published: 25 January 2019

Abstract

Background
Mycobacterium avium paratuberculosis (MAP), an obligate intracellular pathogen, has long been proposed as an aetiological factor in Crohn’s disease. Prolonged, combination antibiotic therapy has shown beneficial effect in the induction and maintenance of remission in a small number of studies but was not replicated in an RCT.1 However, the evidence remains conflicting, particularly with criticisms on experimental design and subtherapeutic antibiotic dosing in the latter. We report the outcomes of this therapeutic option in a selected cohort of patients at our institutions.

Methods
A retrospective study was conducted by examining the records of adult patients commenced on anti-MAP therapy (AMT) at both Guy’s and St. Thomas’ Hospitals and London Bridge Hospital, between February 2011 to December 2017. Treatment regimens were slightly varied but standard therapy was clarithromycin 750 mg OD, rifabutin 450 mg OD and clofazimine 100 mg OD. Hospital notes were used to capture demographic data, disease characteristics and therapy details including indications and duration of therapy. Objective measures of response included at least one of; reduction in CRP or faecal calprotectin, improvement in endoscopic or radiological appearances. Statistical analysis was performed using GraphPad Prism.
Results

In total, 62 patients were prescribed AMT over the study period, 21 were excluded due to insufficient outcome data. 21/41 (51%) were male and median age was 28 (range 18–63) at the time of commencing therapy. The cohort had moderate to severe Crohn’s disease with 26 (63%) having stricturing or penetrating disease and 18 (44%) with previous surgery. Thirty-one (76%) had previously received biologic therapy. AMT was commenced in 26 (63%) patients due to failure of conventional therapy, 3 (7%) in patients where conventional therapy was not appropriate and the remaining due to patient preference. AMT was well tolerated with only 5 (12%) patients stopping therapy due to adverse effects. Nineteen patients (46%) demonstrated at least partial benefit, corroborated by objective evidence in 13/19 (68%). Response was not associated with disease phenotype and duration, previous therapy or use of clofazimine. Those patients who responded had a longer duration of therapy (median 24 months compared with 14 months; p = 0.04) than patients who did not respond.

Conclusions
Our study demonstrates that in a cohort of patients in which the majority failed conventional treatment, AMT was well tolerated and a response was seen in 46%. Patients who responded were on AMT a median 24 months which supports the current recommendation of a 24-month duration of treatment. Limitations include a small, heterogenous cohort of patients.

Reference

1. Selby WS, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007;132:2313–9.
Posted 5/31/2019 4:27 PM (GMT -7)
South East London Area Prescribing Committee - NHS Lambeth CCG

www.lambethccg.nhs.uk/news-and-publications/meeting-papers/south-east-london-area-prescribing-committee/Documents/New%20Medicine%20Recommendations/Recommendation%20066%20anti%20MAP%20therapy%20for%20IBD%20May%202017.pdf
Posted 5/31/2019 6:02 PM (GMT -7)
What's your thoughts on the map-vaccine and the trial results thus far? You seem to follow it closely.
Posted 6/1/2019 1:09 AM (GMT -7)
Everything looks good so far, I want them to complete this as soon as possible - regardless of the outcome. At least we will have an answer to the MAP problem. According to their predictions, they will start enrolling Crohn's patients for the clinical trial in the second half of this year, and since some of the patients in the study will post their experiences online, we will have a clue at whether it is effective or not before the completion of the trial and the publication of the results. I am saying this with some confidence, because they will first test the patients with their diagnostic test for MAP infection, and only accept the patients who are MAP-positive.

"In cattle, inoculating against MAP has proved remarkably effective, according to a study published in October 2014 in Veterinary Research. The vaccine trains cows’ immune systems to kill off MAP in their guts, in many cases leading to permanent relief. The tantalizing question: Might it also work for people?"

"'If it does in humans what it did in preclinical animal trials, the vaccine could have significant benefits for people with Crohn’s disease,' Hermon-Taylor says."

From: https://www.everydayhealth.com/crohns-disease/treatment/cure-crohns-disease-how-hopeful-should-we/

This is the link to the animal study: https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-014-0112-9

They gave the vaccine prior to the MAP infection in calves, and found it an effective preventative. How this will translate into treating already infected humans remains to be seen. Even if it stimulates the successful killing of the MAP in the patients by their immune system, will this actually help their Crohn's? That also remains to be seen.

It's an interesting project, and it should be supported. That's why I am posting about it, to inform people.

Post Edited (xy123) : 6/1/2019 2:27:23 AM (GMT-6)

Posted 6/1/2019 4:42 AM (GMT -7)
I think it's a novel treatment and fascinating. I too hope they're right! I believe UC is suspected to be a different type of bacteria and the same thing could be applied to us, should they be right...
Posted 6/3/2019 11:27 AM (GMT -7)
A review of the Crohn's MAP Vaccine phase 1a study (https://www.crohnsmapvaccine.com/wp-content/uploads/2019/05/jenner-phase1a-paper.pdf) results by Dr. Tim Bull:
https://humanpara.org/expert-review-crohns-map-vaccine-may-2019-research-paper/
Posted 6/5/2019 1:20 PM (GMT -7)
MAP: Just a Suspect or Proven Perp in Crohn’s?
Debate over mycobacterium paratuberculosis as major CD cause mirrors Helicobacter pylori saga

https://www.medpagetoday.com/reading-room/aga/lower-gi/79712?fbclid=iwar3qrsgkpqljzq9or6hhvzwntzbyf0r0gvlrdgklijmrmzehvoxayj5fic4
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