UK Rituximab Research Update

[Jo Best]

Hello everyone, this is my first post on the forum, so please bear with and I expect someone may beat me to it.

Update by UK charity Invest in ME Research on their Rituximab Research (B-cell studies and UK clinical trial).

Full statement here - http://future.cofeforme.eu/IIME-Newslet-1611-03.shtml

Extracts -

In 2013, following the BRMEC3 Colloquium, Invest in ME and its supporters honoured the commitment made by the charity a year earlier, at the IIME7 conference in 2012, to initiate a UK rituximab trial project.

The work progressed with the team at UCL where it was decided early on that a preliminary B-cell study ought to be performed in order to try to replicate the B cell findings of Bansal et al. and to determine likely responders to the drug. This was something that our advisor and the UCL department thought was necessary. This was initiated in 2014. PhD student Fane Mensah is now continuing this B-cell research with Dr Jo Cambridge – again funded by IiMER.

After preliminary B-cell study was underway there was an internal reorganisation in the clinical trials unit (CTU) at UCL which resulted in the principal investigator being moved away from the project and the CTU being downsized. When this was communicated to the charity then we began to look for alternative solutions.

The trial was advertised on our web site in order for interested parties to apply to the charity and at the same time the charity actively continued to look for a place for the trial as the B-cell research continued.

The preliminary B-cell research paper was published in 2016 click here.

After an expression of interest from UEA/IFR it was agreed to relocate the rituximab trial to Norwich Research Park, home for the UK Centre of Excellence for ME.

In January Dr Oystein Fluge and his team will visit Norwich to work with the UK researchers in planning the trial - click here.

The original target for the rituximab trial was set by our advisor back in 2013. Having shown great vision and determination in looking at other areas of research linked to their phase III trial experiences and developing an incremental, evolutionary method of research then we feel the Norwegian Haukeland researchers have exactly the model of how good research should proceed. With the progress made by the Norwegian researchers and the increased knowledge now gained by them it will be interesting to see how the UK trial planning will progress with this new collaboration.

Source - Invest in ME Research Centre of Excellence for ME - http://future.cofeforme.eu/IIME-Newslet-1611-03.shtml

 

[Jo Best]

More news today -

Invest in ME Research have arranged for Dr Øystein Fluge from Haukeland University Hospital in Bergen, Norway, to give a public lecture in #Norwich in January 2017. "We hope to see many at this event in Norwich. Welcome". Full announcement here - http://www.investinme.org/ce-news-1611-04.shtml

 

[justy]

Thanks so much for the update @Jo Best - I had been wondering what had happened to the UK Rituximab study - discussion about it on the forums had gone quiet - or else I've just missed it!

Just wondering how the fundraising is going - who will be the lead clinician and when is it expected to go ahead. Oh and where will patients be recruited from?

 

[Jo Best]

Hi @justy - thanks for replying! I wasn't sure whether updates had been posted here on PR. I had a look but my eyes and brain don't work so well together these days, so I thought I'd go for it and post in the hope that someone would point me in the right direction if the info is elsewhere on the forum.

Just wondering how the fundraising is going - who will be the lead clinician and when is it expected to go ahead. Oh and where will patients be recruited from?

Donations and pledges for the IiMER Rituximab Research so far amount to £500k of the current £520k target and enabled the preliminary B-cell study to get underway without delay and to progress to next phases. So the fundraising is going well and hopefully that will continue so that the research can progress unhindered.

I only know what IiMER have put in the public domain and they haven't given details yet about the lead clinician, patient recruitment, or when the trial is expected to begin, and I expect this will be discussed when the UK team meet again with the Haukeland team in Norwich in January. I've no doubt the charity will publish news or updates as soon as they are able. This is the news page on their Rituximab Research microsite - http://www.ukrituximabtrial.org/IIMEUKRT News.htm
I expect you are signed up to receive their free e-newsletter but here is the link in case not -
http://future.cofeforme.eu/newsletter.shtml

Thanks again for your reply.

 

[Battery Muncher]

Thank you for your very helpful update Jo Best.

I wasn't aware of the issue with UCL and the CTU - I was wondering if you could provide more information on what happened? Also, who are the researchers at Norwich who are taking on this project?

Thanks!

 

[Jo Best]

Thanks @Battery Muncher I only know what's in the IiMER statement (that there was an internal reorganisation and downsizing in the CTU at UCL). Fortunately, that hasn't affected the B-cell research at UCL.

I don't think they've announced which researchers at Norwich will be taking on the trial. The links at Norwich Research Park are well established as it's the base for the IiMER Centre of Excellence for ME and there is ongoing collaboration between the UK researchers and their colleagues in other countries,

Professor Simon Carding (leader of the IiMER gut microbiota in ME research) mentioned a rituximab trial in his presentation at IIMEC11 in June on the European ME Research Group (EMERG).

Professor Simon Carding (Norwich Research Park, UK) talked about the work of the European ME Research Group (EMERG). He stressed the need at addressing biomarkers, including brain imaging. Looking for cause, making a diagnosis and standardisation of samples should be included. A “together approach” is needed. Euromene is a group of researchers hoping to establish a network across Europe. Euromene and EMERG will work together. There is a need to look for opportunities for funding. They will build on current activity and feasibility, such as:

1) Infectious origin
a) environment
b) microbiome alterations

2) Clinical trials
a) Rituximab
b) Bacteria based therapy.

Coming together is a beginning. Keeping together is progress. Working together is success. (Henry Ford)

 

[Jo Best]

Fane Mensah (IiMER-funded PhD student working on the B-cel research at UCL with Dr. Jo Cambridge) is currently in Bergen, Norway, having been invited to be there in the rituximab trial status meeting.

Fane will be presenting there as part of the collaboration with the Norwegian team.
IiMER hope to have an article on the visit later.
Meanwhile they are planning for the January meetings in Norwich,
This is an article written by Fane in 2015 -

Through The Eyes of a Young Researcher -
http://www.ukrituximabtrial.org/Rituximab news-Jan15 01.htm
Lay Summary of the first B-cell paper -
http://www.ukrituximabtrial.org/Rituximab news-Mar16 01.htm

IiMER are also funding an additional student at UCL to assist with the project "B cell function in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Investigations of metabolic function during B cell maturation and differentiation". The aim is to investigate potential differences in B cell maturation, differentiation and metabolism between patients with ME/CFS and healthy controls.

The charity will underpin the extra work with a grant of £9000 to cover the student who will work until early 2017 assisting existing PhD student Fane Mensah and Dr Jo Cambridge.
The team hope to identify whether potential differences are due to alterations in signalling or metabolism in B cells from ME/CFS patients and the additional student resource will hopefully accelerate Fane's project.

 

[Jo Best]

The UCL team are among the first to benefit by the Solve ME/CFS Ramsay Award Program -
http://solvecfs.org/metabolic-analy...ic-encephalomyelitischronic-fatigue-syndrome/

Metabolic Analysis of B-Cell Maturation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
A project summary as written by Geraldine Cambridge, Fane Mensah, and Chris Armstrong:

Many viral and other infectious agents have been reported to cause or trigger the symptoms described by patients with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The variety of pathogens associated with ME/CFS however suggests that a single agent is not responsible and that chronic changes to the normal functioning of immune and other body cells caused by stressors such as infections more likely underly this disease.

ME/CFS patients suffer from a wide range of physical, neurocognitive and autonomic symptoms. It is perhaps therefore not surprising that in the limited biomedical studies so far performed, there appears to be a lack of consistency in results. Understanding the underlying disease-associated physiological and biochemical pathways in ME/CFS patients would therefore allow a more evidence-based approach leading to rapid diagnosis and to potential therapies. At present there are no biomarkers which could link the changes in function of the immune, neurological and other tissues to the many different disease manifestations of ME/CFS.

There is however some concensus amongst researchers that differences from healthy controls exist in both the functioning of the immune system and also in energy metabolism in ME/CFS. Focus on the possible involvement of certain immune cells (B-cells) in ME/CFS has recently been boosted after both investigator and patient-reported improvement in symptoms following removal of B-cells using rituximab. Response to rituximab-based therapy in autoimmunity is usually associated with the presence of disease-associated antibodies which are the products of B cells following maturation. Changes in energy metabolism, including the reduced use of oxygen during aerobic respiration following exercise, reduced antioxidant levels and increases in signals of oxidative damage by reactive oxygen species have also been described by several groups of investigators. All of these relate more or less directly to the function of the mitochondria (‘power-houses’) in cells. A technique called ‘metabolic profiling’ is a powerful tool which can provide detailed information about the biochemical signals and patterns related to mitochondrial function. This technique can be used to analyse mitochondrial related ‘signals’ in blood, urine and also in cultured cells.

The aim of this study is to investigate potential biochemical pathways that may be implicated in the development and chronicity of symptoms in ME/CFS patients and HC. We will be focusing on studying the metabolic functioning of mitochondria from B cells as there is evidence that changes in metabolism will affect the way these cells mature into antibody producing cells.

Researchers at University College London were the pioneers of rituximab-based therapy and have an established reputation in B cell research in autoimmune diseases and ME/CFS. Metabolic profiling by Dr Armstrong (University of Melbourne) has provided evidence for chronic immune activation impacting mitochondrial function in ME/CFS patients. The current application is therefore a unique collaboration between two committed young researchers under the supervision of experienced supervisors in different centers of excellence.

2016 Ramsay Award Program Results -
http://solvecfs.org/2016-ramsay-award-program-results/

 

[Jo Best]

Just saw this tweet. I love the informal photos

https://twitter.com/i/web/status/802447177486319616

 

[Jo Best]

Bit of festive cheer with the latest funding update courtesy of Jan Laverick http://www.investinme.org/ce-news-1612-01.shtml

 

[Jo Best]

Info on the January 2017 meeting at Norwich Research Park posted by IFR today - http://www.ifr.ac.uk/news/events/2017/01/mecfs-biomedical-research/

 

[Jo Best]

New Year summary on Let's Do It for ME blog - http://ldifme.org/2017/01/03/from-norway-to-norwich-iimer-rituximab-research/

 

[Jo Best]

Agenda for the evening talks in Norwich today 26th January 2017 - http://www.investinme.org/ce-news-1611-04.shtml

 

[Jo Best]

If you are in UK or can access this, pleaese view and share this excellent BBC Look East regional TV news report -
http://www.bbc.co.uk/iplayer/episode/b08bbztq/look-east-late-news-26012017
It's also on youtube -

 

[Jo Best]

Studio interview with Prof Simon Carding in the late evening news of 26th January -

 

[Jo Best]

ME/CFS talks held in Norwich - http://www.ifr.ac.uk/news/latest-news/2017/02/mecfs-talks-held-norwich/ Article includes link to talks now on IFR YouTube.

ME/CFS talks held in Norwich
Date 7 February 2017

An event held in Norwich in January 2017 gave the public a chance to hear about some of the biomedical research being undertaken on the debilitating condition ME (Myalgic Encephalomyelitis).
The event was hosted by IFR and Invest in ME Research, a charity promoting biomedical research and education into ME, which is aiming to establish a UK centre of excellence, to improve ME diagnosis and coordinate research into treatments and cures.


The talks were introduced by Dr Ian Gibson, former MP for Norwich North and from the Invest in ME Research Advisory Board.

Speakers (click to jump to their talks)

• Simon Carding
• Kari Sorland
• Ingrid Rekeland
• Øystein Fluge

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic disease causing long-term health problems, characterised by severe exhaustion, as well as pain and dysfunction of the brain, gut and immune system. ME/CFS has no effective treatments, and its causes still remain unknown

Tackling ME, and bringing hope of relief to the estimated 250,000 sufferers in the UK needs high quality biomedical research and international collaboration.

Dr Øystein Fluge, a senior consultant and oncologist at Haukeland University Hospital in Norway spoke about ground-breaking research he is leading on Rituximab. This drug has been used to treat leukaemia and lymphoma, as it targets B-cells, a type of blood cell. In 2004, Dr Fluge noticed that ME patients being treated for lymphoma with Rituximab also saw substantial improvements in their ME symptoms. Subsequently pilot studies and a randomised, blinded, placebo controlled study also showed positive results, with a large, multi-site Phase III clinical study now running.

Dr Fluge was visiting Norwich to discuss future collaborations over another Rituximab trial being carried out on the Norwich Research Park with Professor Simon Carding from the Institute of Food Research (IFR) and University of East Anglia. Professor Carding also introduced the audience to research in his own group, who are looking for causes and treatments for ME in the gut and its microbial communities. The Norwich Research Park is establishing itself as a hub for biomedical research into ME, in the UK and Europe and through international collaborations.

More information
For more information, please follow Invest in ME Research and our own websites and social media channels. Whilst we are working closely with the group of Dr Oystein Fluge in Bergen, Norway to help with the development and planning of a trial in Norwich similar to the ones currently underway in Norway, if the results from the Norway trial are positive. The outcome of this trial is critical to determining what we would plan to do in Norwich. Until this is known, and we have consulted with clinical colleagues, it is impossible to say what a future Norwich trial will consist of, or what the recruitment process will be.

 

[Jo Best]

Links to the BBC Look East TV news clips on YouTube and the public talks are all now on this page on Invest in ME Research website - http://www.investinme.org/IIME-Newslet-1701-02.shtml

 

[Jo Best]

From Invest in ME Research newsletter 12th February 2017 -

FROM NORWAY to NORWICH - POSTSCRIPT

The workshop to plan the UK rituximab trial took place in Norwich Research Park as planned with members of the Norwegian Haukeland University Hospital RituxME team visiting the UK research team at the end of January.

Dr Øystein Fluge, Kari Sorland and Dr Ingrid Rekeland joined with the IiMER-funded researchers, including Professors Simon Carding and Tom Wileman, Professor Angela Vincent and Dr Jo Cambridge and Fane Mensah. Others from the Norfolk and Norwich university Hospital, Clinical Trials Unit and the local ME service attended and a very interesting and productive workshop took place. We were pleased to have Chris Armstrong present for part of the discussions. Chris has been in London working with Fane.

Read more - http://www.investinme.org/IIME-Newslet-1701-02.shtml

RESEARCH NEWS from FANE MENSAH

Fane Mensah is being funded by Invest in ME Research for the B-cell research at UCL with Dr Jo Cambridge[The potential role of B cells and their products in ME/CFS Patients]

This crucial work has been continuing and is augmented by a recent collaboration with Chris Armstrong from Australia. Fane and Chris met at IiMER's #BRMEC6 Colloquium in London in 2016.

Fane has kindly produced this update - showing the importance of continuing this research and of international collaboration. And the funding given by IiMER to help with students contributing to these studies demonstrates the importance of continued fundraising attempts to maintain our support for high-quality research.

Read more - http://www.investinme.org/ce-news-1702-01.shtml