MS CAP Protocol Variation or Add-On: Step 1 CAP, Step 2 - Speed Up Re-Myelination??
MS CAP Protocol Variation or Add-On: Step 1 CAP, Step 2 - Speed Up Re-Myelination?
I dream of a day when no person on this planet has to go through what Rick, one of my sons, and many here have gone through. I think it's possible - and would bet the very first line of defense could end up being Vitamin D3 level monitoring and supplementation when need be from a very early age. That said, having found the CAP protocol is a wonderful thing. I believe the next step for Rick that he can take during his CAP protocol - is to add Clemastine Fumarate (an Over the Counter antihistamine!) to his regime, to hopefully "boost" the re-myelination process. Of all the things I've seen so far, e.g. the other research efforts I've read about and other drugs in development, Clemastine appears to have the most immediate and actionable promise in assiting with re-myelination. I also believe that it's very likely to be proven true that those who deal with the underlying issues first (a cap protocol) are far more likely to see Clemastine be effective at stoping and reversing their disease than someone just taking Clemastine.
A special thanks to Arttile – who, as far as I know, was the first member of this forum to find articles on the web about Antihistamines and their potential role in re-myelination. And, to Irene for being willing to share her experience on her CAP protocol combined with Clemastine Fumarate.
This summary is intended to be posted in cpnhelp.org as well as to be sent to other folks I know with Multiple Sclerosis or with family members, relatives or friends with MS.
I’ll start with a brief review of what I’ve learned over the last 18 months about potential treatment options not currently endorsed by or approved by the FDA and similar institutions world-wide, but none-the-less very much worth considering by someone with Multiple Sclerosis:
- With the premise that MS may be caused or greatly exacerbated by a common pneumonia germ, Chlamydia Pneumonia (cpn) – many folks at WWW.CPNHELP.ORG have undergone or are currently undergoing successful treatment with a “Combined Anti-Biotic Protocol” (CAP) along with supplements to support ridding their bodies of the toxins resulting from the “die-off” of the suspected germ.
www.cpnhelp.org – a terrific resource about Chlamydia Pneumonia (CPN), the diseases it’s implicated in, it’s treatment, and the experience and wisdom of a group of folks committed to getting better, and helping others get better, by treating their CPN.
MS Cure Youtube - A moving summary of cpn / cap and Doctor Wheldon's desparate search for a "cure" for MS for his beloved Wife Sarah.
http://www.davidwheldon.co.uk/ms-treatment.html - Dr. Wheldon’s website on MS.
- A Neurologist in Brazil credibly claims to have treated about 2,000 patients with a 95% success rate – using Vitamin D3 at very high doses. Vitamin D3 appears to stimulate production of small proteins in the body that have anti-biotic effects, and thus it appears that the Megadose D3 regimen may be very synergistic or complementary to the CAP protocol. Use of D3 at the dosages mentioned by this Doctor should likely be done only under the supervision of a Doctor. Lower doses none-the-less most likely provide significant therapeutic benefit. Well tolerated high doses are in the range of 5,000 IUs to a high maximum of 20,000 IUs. Additional supplements are advised, in particular Vitamin K.
http://www.vitamindwiki.com/Autoimmune+disorder+patients+in+Brazil+helped+by+vitamin+D+%E2%80%93+video+and+Facebook+%E2%80%93+Nov+2012 – there are lots more articles and a facebook page that can be found. This subject sparked a rather lively debate on cpnhelp.org for a bit, so a search of forum posts will find lots of information. Additionally, cpnhelp.org has a special section on the importance and role of Vitamin D 3 here:
Vitamin D3 may be something that can be substituted for N-Acetyl Cysteine, though this should be commented on by a Physician.
- Recently, two separate groups (Research Doctors at UCSF, Scripps Research Institute) – have screened already FDA approved drugs using an advanced “high-speed screening” process and identified 8 drugs in the same “class” of drugs that appear to promote the differentiation of Oligodendrocyte Precursor Cells (OPCs) into mature Oligodendrocytes and their proliferation through the brain. Oligodendrocytes are the cells that re-myelinate axons in the brain and central nervous system. Subsequently, there was a Phase II Clinical Trial instigated to test the drug on 50 patients and originally scheduled to conclude in September of 2014.
From all indications a company, www.Glialogix.com - was formed with the intent to commercialize one of the top 8 drugs identified. The drug in question is available Over-The-Counter in the US, though supplies appear to be shrinking.
Known by the trade name “Tavist” – Clemastine Fumarate is a first generation “Anti-Histamine” with “Anti-Muscarinic” properties that is very closely related to “Benedryl” aka diphenhydramine. The dosages being tested in the Phase II clinical trial are 4x the normal daily adult dosages.
Given clemastine and similar medications have potentially severe side effects, folks who decide to undergo a course of treatment today rather than wait for the results of a Phase III clinical trial should proceed with all due caution and most likely slowly ramp up the dosage.
In the U.S. Clemastine Fumurate is available at drug stores – including Walgreens, Walmart, CVS, Target and others, usually as a company branded anti-histamine (Wal-Hist for Walgreens version).
The first of the above 3 therapies may provide a means to stop the progression of MS. Many folks on the forum www.cpnhelp.org state that treating their disease with a CAP protocoal has halted their disease and in many cases, their disability has improved, sometimes remarkably.
Given Vitamin D3’s antibiotic properties, D3 may not in itself provide more benefits than the CAP protocol, it may however provide an alternative to the documented “first line of defense” – commonly used by folks on the forum after completion of the CAP protocol to prevent re-infection. It may, in other words, be something folks can substitute for N-Acetyl Cysteine, or NAC.
While Clemastine is a very old drug (50 years?) the use of Clemastine to treat MS is of course still very new. Having said that, Clemastine holds out the promise of speeding up recovery and potentially recovering more than the CAP treatment alone may achieve. Importantly, Clemastine Fumarate is available over Over-The-Counter now, there is no need to await the results of a clinical trial that might take 5-10 years to complete.
This forum topic for CPNHELP.ORG is to provide more details on number 3 above, as the details for numbers 1 and 2 are well covered elsewhere in the forum.
Research on Anti-Histamine and Anti-Muscarinic Pathways in Ogliodendrocytes:
While most of the research and development in the Scientific and Medical Community seems to have been centered around the premise that MS is an “Auto-Immune” disorder, there are many researchers and organizations (UCSF, Scripps Research Institute, Stanford, others) that have been researching ways to encourage re-myelination in the brain. Several different strategies are being explored, some quite exotic (stem cells, “small molecules”) and with timeframes for availability to the public likely 5-10 or more years away.
A very exciting recent development, apparently discovered by at least two different institutions and in close to the same timeframe – is the use of Anti-Histamine Compounds very closely related to Benedryl (diphenhydramine) – including compounds in the same overall family but used to treat Over-active Bladder symptoms, Parkinsons, and other disorders.
The advantage to the companies that might bring these compounds to the public as FDA approved products is that the safety profile and side-effects are already very well established – allowing them to skip phase I clinical trials and move into phase II and phase III clinical trials much more quickly and without as large an expense.
For those unwilling to await the results of the clinical trials, the advantages are the drugs are easily obtained and most likely without a doctor’s prescription, the risks and side-effects are well understood overall (though not necessarily in the MS population given the special requirements this group may have as well as other medications they may be using – e.g. overactive bladder meds from the same family may represent a risk). That said, like Antibiotics, the risks are low and understood, and in the context of MS, the rewards may far outweigh the risks.
Scripps Research Institute’s “high speed screening” of over 100,000 drugs, identified Benzotropine as the top compound. Benzotropine is used to treat Parkinsons and likely would require a supportive Doctor to write a prescription. The University of San Francisco’s high speed search identified Clemastine Fumarate (Tavist) as the top compound, along with 7 other compounds, including Benzotropine.
Clemastine Fumarate is available “Over-The-Counter” – and is at the least still commonly carried as a generic alternative to “Tavist” – by the likes of Walgreens and Walmart, among others.
Clemastine Fumarate - a "Magic Bullet" to help with Re-Myelination?
Clemastine and similar medications appear to have two pathways that may have an effect on Oligodendrocytes. The first is the “Anti-histamine” pathway. Histamine is associated with allergic reactions, including over-reactions.
Clemastine is an Anti-histamine – through being an antagonist to the H1 Histamine Pathway. The anti-histamine effects appear to turn down the production of Glutamate in the brain, and may be beneficial as too much glutamate can kill brain cells, including oligodendrocytes and other support cells in the brain:
Histamines can cause over production of Glutamate, apparently, and thus an antihistimine seems likely to do the opposite through some mechanism. I'm sure there are lots more articles out there - but here is one:
http://www.sciencedirect.com/science/article/pii/S001429999700143X - "Histamine modulates glutamate release ....”
Anti-Muscarinic (muscarinic blocker) -
Using “M3 Muscarinic” as a search phrase, the first research article found in NCBI from 2003:
“In conclusion, modulation of muscarinic receptor sensitivity may have functional implications for the developmental progression, terminal differentiation and survival of oligodendrocyte progenitors in response to acetylcholine released by neurons.”
The context appears to be up and down regulation of the sensitivity of Oligodendrocyte Pre-Cursors to an agonist to the M1 or M3 Muscarinic acetylcholine receptors.
These same receptors were later found to encourage or induce the differentiation of Oligodendrocyte Pre-Cursors into Mature Oligodendrocytes and their subsequent proliferation through the brain:
“To identify selective inducers of oligodendrocyte differentiation, investigators at The Scripps Research Institute (La Jolla, CA, USA) performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. They screened over 100,000 chemical compounds for any that could potently induce oligodendrocyte progenitor cells to differentiate.
The investigators reported in the October 9, 2013, online edition of the journal Nature that benztropine was among the most effective of the compounds that were screened. Furthermore, it significantly decreased clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis.
Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays, and EAE adoptive transfer experiments indicated that the observed efficacy of the drug resulted directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicated that benztropine functioned by a mechanism that involved direct antagonism of M1 and/or M3 muscarinic receptors.”
Both of the above studies used “high speed screening methods” – and both identified compounds that have M3 muscarinic antagonist effects. Clemastine and Benzotropin were two of the top compounds identified. One, Clemastine – went on to be tested in a Phase II clinical trial:
https://clinicaltrials.gov/ct2/show/NCT02040298 - government side
Researchers in Dr. Lawrence Steinman's laboratory at Stanford:
http://www.ctsaip.org/create-pdf.cfm?id=5893 – About “benedryl” – and antihistamines to “ameliorate” the course of MS. Well - diphenhydramine has known M3 muscarinic blocking effects. Clemastine belongs to the same family of compounds.
And - Dr. Lawrence Steinman has apparently applied for a patent on the use of H1 Blockers (Antihistamines) - to treat autoimmune diseases, including MS:
http://bit.ly/NRE0BI - this will downloade a PDF article, very arcane.
Irene and others using similar compounds report “dramatic improvements:”
The results of the Phase II clinical trial in UCSF have not been posted, though they were due by November of 2014. In the meantime – a company has been formed that appears to be poised to commercialize Clemastine Fumarate for “Progressive MS” (including SPMS and PPMS). This firm – www.glialogix.com – talks about their drug in the context of lowering glutamate:
"GLX1112 inhibits a novel drug target present on neuroinflammatory cells that generates excessive glutamate levels in the central nervous system. Excess glutamate levels overexcite neurons and oligodendrocytes, leading to aberrant neuronal signaling and cellular damage. This damage can further exacerbate neuroinflammation. By inhibiting excess glutamate, GLX1112 is designed to block both glutamate excitotoxicity and neuroinflammation. In addition to being neuroprotective, this mechanism of action is applicable to symptoms of progressive MS, including neuropathic pain and cognitive deficits. It is also consistent across multiple neurodegenerative diseasesi and has been validated in preclinical models of MS, ALS and neuropathic pain."- from Glialogix’ website.
While they make no mention of any M3 Muscarinic Blocking properties for their compound, there are numerous clues that suggest they likely are working to commercialize Clemastine Fumarate to help with re-myelination. The clues are; 1) Physical proximity to UCSF 2) Timing of their announcements 3) Board Members from UCSF 4) Mechanism of action reported (see above) and 5) Board Members familiar with “high-speed” screening.
The UCSF trial tested (or is testing) 4x the daily adult dose of Clemastine Fumarate:
Clemastine Fumarate and similar compounds (Clemastine is a member of the diphenhydramine family: http://www.makehumans.com/htmx/H1_antagonist.php) are known to have some very serious and even potentially fatal side effects (serious and fatal side effects are associated with gross over-dosage, not with normal dosages), so the use of them should be done with caution. Similar drugs from the same family likely should not be combined (e.g. benedryl and clemastine probably shouldn’t be taken together). Additionally, warning labels for toxic levels should be read and the cautions observed.
All that said – 4x the daily dose is 4mg 2x a day – while a member here has decided to go with 2x the daily dose with minimal side effects, which reportedly disappeared after the first week.
Ramping up and watching for side effects seems reasonable given the potential rewards – e.g. repair of damaged Central Nervous System through re-myelination of demyelinated axons caused by CPN mediated Multiple Sclerosis.
Those unable to find Clemastine Fumarate, or who want to try a lower cost more easily available alternative, may want to consider Benedryl aka Diphenhydramine. A “trial” may shake out whether it would be helpful or not – and apparently not a long drawn out trial (see the two links that reference "dramatic improvements - above, and in a relatively short timeframe).
"Clemastine holds out the promise of speeding up recovery and potentially recovering more than the CAP treatment alone may achieve. Importantly, Clemastine Fumarate is available over Over-The-Counter now, there is no need to await the results of a clinical trial that might take 5-10 years to complete."
My best wishes and prayers that each of you has as fast, smooth and complete a recovery as God and Modern Medicine (cap for cpn) will provide.
Best & Highest Regards,