France: Bio-Modelling Systems to start phase II clinical trial(s)

cassava7

Senior Member (Voting Rights)
Recent news apparently, for what it's worth. They are the bioinformatics company that the French association for CFS have partnered with, though we members haven't received any details.

They have set up a page on their website about ME, where they present their understanding of its pathophysiology (unproven claims): https://www.bmsystems.org/cfs-me
BMSystems’ heuristic CADI™ Discovery model proposes the first treatment for CFS/ME by integrating the pathology's immunological dysregulations with their systemic metabolic, physiological and cognitive consequences. The model developed in close collaboration with the French Chronic Fatigue Syndrome Association provides thorough understanding of the causal CFS mechanisms and their modes of clinical progression. The treatment, already validated by a clinical proof of concept will enter in a phase II clinical trial with our partner.

More info on CADI: "Computer Assisted Deductive Integration"; slides from a 2011 presentation at the European Congress of Psychiatry:

ETA: they have published a leaflet on post-COVID19 ME.
 
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Chronic Fatigue Syndrome/Myalgic Encephalomyelitis remains a debilitating condition for the patient and a confusing one for the physicians, both because of diagnostic difficulties and poorly codified management. Despite numerous studies, its pathophysiology remains unclear, but a multifactorial origin is suspected with triggering (infections) and maintenance (psychological) factors as well as the persistence of inflammatory (low-grade inflammation, microglial activation…), immunologic (decrease of NK cells, abnormal cytokine production, reactivity to a variety of allergens, role of estrogens…) and muscular (mitochondrial dysfunction and failure of bioenergetic performance) abnormalities at the origin of multiple dysfunctions (endocrine, neuromuscular, cardiovascular, digestive…).

If this is the starting understanding of CFS/ME, I doubt that Computer Assisted Deductive Integration is going to help much.

CADI™ discovery is a problems solving approach evaluating each step in a process, searching for satisfactory solutions rather than for optimal solutions, using all available qualitative information instead of quantitative information.

GIGO
 
The treatment, already validated by a clinical proof of concept will enter in a phase II clinical trial with our partner.

I had a look at all the stuff linked, but couldn't find anywhere what the treatment being tested actually involves. Lots of fancy diagrams, but no specifics - drugs? nutrients? therapy? I'm bemused. Did I miss something? Is there a protocol for this trial registered anywhere?
 
I had a look at all the stuff linked, but couldn't find anywhere what the treatment being tested actually involves. Lots of fancy diagrams, but no specifics - drugs? nutrients? therapy? I'm bemused. Did I miss something? Is there a protocol for this trial registered anywhere?
None -- you didn't miss anything. The association might release a bit more info soon-ish but they're under non-disclosure agreements.
 
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They are preparing a phase 2 clinical trial for a combination of already approved medication. No info given as to what this combo might be.

They haven't done a phase I trial, because they say that the individual meds in this combo are not toxic and so the combo shouldn't be toxic either. So they don't expect health authorities to ask them to do a phase I trial.
 
They haven't done a phase I trial, because they say that the individual meds in this combo are not toxic and so the combo shouldn't be toxic either.

Hmmm.....I don't think that just because drugs might be safe individually it necessarily follows that they'll be safe in combination unless they are very confident in their knowledge of both individual drugs.

I suppose if they're existing & well known drugs they might have reason to be.

I guess we'll find out. Eventually.
 
BMSystems were interviewed in Global Benefits Vision about the risk of post-COVID19 ME/CFS. They provide more information about their upcoming clinical trial and their scientific understanding of the disease,

About ME/CFS itself

Their description of ME/CFS (p. 32) does not include PEM, but the Venn diagram figure underneath the description does and ME/CFS is presented as:
a complex and devastating disease that imposes a burden of illness on millions of people around the world. It is a serious, chronic, and complex systemic disorder

On page 36, they present the context around ME/CFS quite well. They mention important issues such as the different diagnostic criteria, the absence of medical education and of a biomarker, the underdiagnosis of ME/CFS (cites IOM report), and there's also this relieving part:
Alternatively, unconventional medical therapies, counselling and cognitive behavioural therapies (CBT) are frequently implemented, although with little or no evidence of improved symptomatology. These often reflect the mis-conception that CFS/ME is a psychological condition, when in reality it has a clear pathologic immunological basis.

Their understanding of the pathophysiology of ME/CFS (pp. 33-35)

They understand ME/CFS as "an inflammatory disease" caused by "the superposition of humoral and cellular responses" (diagram on p. 35).
Our research shows that CFS/ME is an inflammatory disease, caused by overlapping immune responses that misguide the actions of the immune system.

In a nutshell, this inflammatory condition can occur when a chronic, low-level, and often asymptomatic inflammatory reaction that biases the immune system towards cellular responses is superimposed on an acute infection that triggers a humoral response opposed to the first.

The first condition, which can drive a person’s immune system to adopt a long-lasting strategy (or a polarized/biased response), is often due to a chronic viral infection with a double strand DNA virus such as are HHV, HSV, EBV, CMV, etc. More than 90% of people are exposed to these chronic dsDNA viruses by three years of age. The virus DNA can insert itself into a chromosome and remain latent in just a few cells for years, silently being copied each time the cell divides. Even if for most people this causes no problem, it can set the inflammatory background allowing the occurrence of CFS/ME for some others. This of course depends largely on the genetic and environment factors that shape an individual’s immune system.

[...]

The second condition, which could cause the immune system to adopt an opposing and conflicting strategy, leading to that particular low grade pro-inflammatory tuning, can be triggered by acute infections from positive-sense single-stranded RNA viruses (ssRNA). One of the most common triggers of CFS/ME is acute viral infections such as those provoked by the influenza ssRNA virus. As an example, a Norwegian national study showed that the percentage of CFS/ME occurrence doubled following the 2009 influenza A (H1N1) pandemic.


The clinical trial/treatment: CADI-T1031

A personalized treatment, apparently.
CADI-T1031 is a “disease-centric repositioning” of existing molecules.

BMSystems’ lengthy experience in immunology/inflammation suggests that there may not be a universal treatment for all CFS/ME patients, as immune function varies from person to person depending on genetic, pathologic and environmental backgrounds. Our diagnostic tools are therefore designed to monitor the patient's immune status, and the treatment is then tailored, using standardized pharmaceutical combinations, much like assembling Lego bricks, to match the patient's actual condition.

Two phases: an "immune equilibration" treatment (2-6 months) to resolve immune dysregulation, followed by an "energetic rehabilitation treatment" (6 months - 2 years). A maintenance treatment could be given afterwards.

They say the combination of drugs used is non toxic and has no side effects.
The treatment is divided into 2 main therapeutic phases. The immune equilibration treatment aims to resolve the on-going conflicting immune strategies and phase out the self-propagating inflammatory reaction. This phase is expected to last from 2-6 months depending on patient’s follow-up and evaluation. The second phase is an energetic rehabilitation treatment, which aims to restore the patient’s energy metabolism that is severely deregulated in CFS/ME, while simultaneously supporting the newly reached immune equilibrium. This phase is expected to last anywhere from 6 months to 2 years, depending on patient’s evaluation. Back and forth between Immune and Energetic treatments is not excluded in cases where the patient’s immune system is dysregulated during rehabilitation, due to occurring infections or underlying pathologies. Finally, a maintenance treatment could be administered at will to cover the patient’s fluctuating metabolic needs. It is important to note that all the components in each phases of the CFS/ME treatment have no toxicity and no known side effects, either individually or in combination.


Post-COVID19 risk of ME/CFS

Page 34:
Coronaviruses are all positive sense ssRNA viruses, and among them, Sars-Cov-1, Mers-Cov and Sars-Cov-2 are known to cause very acute infections and inflammatory syndromes.
[...]
It appears therefore quite probable that the current coronavirus epidemic, caused by the positive sense ssRNA SARS-CoV-2 virus, might trigger a worldwide spike in CFS/ME. However, it is far too early to estimate what proportion of the exposed populations may go on to develop CFS/ME as the formal diagnosis requires symptoms that last for at least six months.

They cite the post-SARS studies from Lam & Modolfsky (p. 34), Mady Hornig's report for Solve CFS (p. 31), and a number of articles about the risk of post-COVID19 ME from the New Scientist, the Guardian, ME Association, the Telegraph (p. 40)

[1] Manuel Géa, Dr. Athanasios Beopoulos, Dr. François Iris. "Life after COVID-19: dealing with Chronic Fatigue Syndrome?". Global Benefits Vision, Issue 47 (April 2020). https://www.bmsystems.net/download/...ssue-047-BMSystems-CFS-Post-Covid-19-2020.pdf
 
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if something sounds to good to be true it is to good to be true ... when will this trial start?
 
I had a look at all the stuff linked, but couldn't find anywhere what the treatment being tested actually involves. Lots of fancy diagrams, but no specifics - drugs? nutrients? therapy? I'm bemused. Did I miss something? Is there a protocol for this trial registered anywhere?

@Trish, I think their treatment is one (or more) of a grab-bag of common psychotropic drugs given in conjunction with a "connexin-blocking agent" (usually meclofenamic acid) which is claimed to potentiate the action of the psychotropic drug so that it can be given at a lower dose. [*]

The patent suggests that the following (somewhat broad) range of conditions may benefit from the drug combination: "psychiatric and/or neurodegenerative disorders included in the group consisting of depression, bipolar disorder, epilepsy, schizophrenia, generalized anxiety, depression, conditions due to stress, panic, phobias, obsessive compulsive disorders, behavioral disorders, immune system depression, fatigue and symptoms associated with pain, chronic fatigue, fibromyalgia, and other disorders such as autism, attention deficit, hyperactivity, eating disorders such as bulimia, anorexia, obesity, psychic disorders such as apathy, migraine, pain, cardiovascular diseases, neurodegenerative disorders and disorders associated with depressive anxiety (Alzheimer's disease, Huntington's disease, Parkinson's disease), drug dependence and drug addiction."

[*] Use Of Anti-Connexin Agents For Modulating The Therapeutic Effect Of Psychotropic Drugs

Applicants: Commissariat A L'Energie Atomique Et Aux Energies Alternatives, Paris (FR); Bio Modeling Systems Ou Bmsystems, Paris (FR)

Inventors: Franck MOUTHON, Paris (FR): Mathieu CHARVERIAT, Issy Les Moulineaux (FR); Jean-Philippe DESLYS, Le Chesnay (FR); Francois IRIS, Chaville (FR)
 
Merged thread

Interview about BMSYSTEMS with Manuel Géa, Dr. Athanasios Beopoulos and Dr. François Iris

I believe that BM Systems of France are undertaking some ME/CFS research and a national ME/CFS organisation is working with them in some way.

https://www.global-benefits-vision.com/life-after-covid-19-dealing-with-chronic-fatigue-syndrome/

INTERVIEW WITH BMSYSTEMS ADDRESSING THE POTENTIAL CONNECTIONS BETWEEN RECOVERED COVID-19 PATIENTS AND CHRONIC FATIGUE SYNDROME/MYALGIC ENCEPHALOMYELITIS (CFS/ME).
THE LINKS ARE COMPELLING, AS IS THE POTENTIAL IMPACT ON EMPLOYERS AND INSURERS.

Manuel Géa, Dr. François Iris, and Dr. Athanasios Beopoulos

As we are reaching near global consensus that business needs to resume, and countries ease lockdown, Global Benefits Vision explores the possibility of a link between COVID-19 and CFS/ME, highlighted by BM Systems of France led by Francois Iris and Manuel Géa, and how employers and insurers can prepare for such an outcome from an employee wellbeing perspective.
 
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Contains no details whatsover, but makes some bold claims. Best not to expect anything from this group.
 
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Contains no details whatsover, but makes some bold claims. Best not to expect anything from this group.

I saw the webinar ... I am French, member of the ASFC (French patients association of cfs), you will not have more information than Cassava has to give here because of the restrictions of commercial information that they must respect. This is the only way to find a partnership with a company that can work with BMS for the different stades of AMM. and distribute the medical solution.
They are very confident about their disease mechanism and the success of their treatment. stages II and III should take place in 2021-2022 for acceptance by French social security in 2023 if efficient. It's the first time until many time that i have hope ...
they said that they'll published soon about the mechanism. (but my memory isn't enough good to remember more info about this part; when the replay will be available, i'll complete my message)
 
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