Jean-Pierre Le Rouzic
Forum Replies Created
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There are several (many?) people that tell on Internet that RCH-4 slowed the progression for them, but this kind of statement does not mean much. How to be sure if their ALS would have progress quicker without RC4? We have no good way to measure ALS progression and too often the ALS diagnostic is a catch all “you have some disease involving motor neurons“.
Apart the RCH-4 controversy, there is an incredibly high number of drugs that were patented to mitigate some aspect of ALS. Many are legal traps.
Filling a patent is not something companies do lightly, as it costs a lot of money. Usually they fill a patent after human trials because at that time they know it is a safe bet. Some patents are dropped afterward because the company did not pay the annual patent fee, often because the inventor left the company and nobody wanted to take care of her/his work load, or the company was bought by a competitor with different goals, etc. RCH4 might possibly be one of such case.
Some ALS patents are fascinating such as this one about regrowing neurons in the CNS:
There was a scientific article in 2014 that was heavily cited, but the patent was filled only four years later, so probably they have some confidence in their findings.
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Hi Diana,
The article that you point out, summarizes well what is important to know about Nurown, at least from my perspective.
I have no confidential information, it seems to me that sooner or later the FDA would authorize it, hopefully late 2020 or 2021 and only if the phase III trial goes well.
About ease of administration I think the patient experience is comparable to an epidural administration.
My guess is that the effect will not be too strong and will not last, because it is a stem cell therapy at the root and stem cells therapies are not well mastered at the moment. Another difficult point is that in ALS neurons and muscle cells are supposed to die, and replacing them is not something that could be done today in the CNS (all hope is not lost as this happens in the PNS).
But I am not a doctor nor a scientist, and I am not a US citizen so I may not understand subtleties in US healthcare.
There are posts by a pALS (Matt Bellina) who received three Nurown injections, for example:
https://www.facebook.com/matt.bellinski.7/videos/10107987655176853
My personal opinion is that this is a step in the right direction, but it will need further improvements and perhaps it will have to be used in combination with other drugs, such as a TDP-43 genetic therapy in order to stop the progression and restore functions.
Jean-Pierre
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You may refer to this study:
https://doi.org/10.1111/ene.13986
I do not think they found a causal link between antibiotics and ALS, what they found is a good correlation. I cite them :
       As a result, even though we did the analyses based on a causal hypothesis, the findings are only suggestive and cannot prove causality.
But scientists have found correlations between ALS and many things including water bodies and weather!
In this later case (weather) they thought it is simply because there are more enterovirus (and possibly others) during some seasons than in others.
As for Glenn, many pALS had some large injury. For me this is more plausible as a cause than antibiotics, at least for a common sense reason: ALS is focal, it starts at one or two precise locations then spreads. it is easy to associate conceptually with an injury. Antibiotics are not focal.
Another thing is that the causative mechanism of ALS may be irrelevant to find a cure.
A cure must not only stop the disease, but it should restore functions. And restoring muscles and neurons cells is beyond our current capacities. However such drugs like Nurown are a good step in the right direction.
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Your “baby-like crawling” text is very inspiring Dagmar!
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Hi Mary,
There are a lot scammers out there, most claim to be doctors and some even claim to be pALS! The mental cost of ALS is excruciating, most people trust whatever they see if there is a slim possibility of hope.
What can be said for sure is that real medical doctors and scientists do not known any way to deal with ALS as a disease, but drugs can make the life more comfortable. Some doctors prescribe anxiolytics, and muscle relaxants, they also happen to prescribe vitamins, including vitamin D.
Some pALS have put forward their own proposals for treatments, usually is consists of a long list of pills. Some minds even tell that ALS is due to an imbalance of (put some impressive scientific name here). I tried to follow this topic for the last six months and I did not see anything very striking.
One main problem is that there are many ALS sub-types and there are many diseases that looks very like ALS (like Wilson disease which is curable). Remissions are extremely difficult to trust because neurons are the longest cells in the body and they do not divide at all. Even replacing them with stem cells is unlikely. Stopping the disease may exist but as there is no biomarkers for ALS, the ALS diagnostic is by exclusion, it is not a very reliable, contrary to diagnostics about communicable diseases. Some pALS tell their diagnostic was refined. And the process for ALS diagnostic is often two years long.
So when someone claims some drug, some “DIY protocol” had cured them, often it simply means that this person did not had ALS, but another disease (an ALS mimic) in the first place.
One person (jcexpress) says that a lot of lab tests must be made and any abnormalities must be corrected. It sounds to me as quite reasonable.
I would advice to find “a good doctor” (in most countries there are ALS centers), to work closely with her/him, and to be careful with the incredible number of proposals on the Internet. Keep your money for you, if you have ALS you will need to buy/rent a lot of things.
Good luck
JP
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Hi Mary,
The term ALS may imply very different life stories, some are horrible but it seems many people are able to cope with their condition. Basically it depends if one has a fast or a slow progression. If it is slow one can cope with it by adapting their environment. If it is a fast progression, then one has only months to make the transition easy for oneself and for the family. Nobody can predict in advance how ALS will evolve, so you can hope for the best outcome.
Dagmar has some really good advices!
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I am sorry for your loss Amanda.
A few observations on this text you linked:
* SOD1 mutations cases are only a few percent of all cases. In fact ALS is very diverse disease, in UK they do not use this word, they use “motor neuron diseases” and I think that it is much more accurate. But most diseases of the Central Nervous System share many features, so it might be that there is no ALS, SMA, Down, FTD, Alzheimer, Parkinson, etc… but proteinopathies. A good step in this direction is for example http://www.alzforum.org
* Having diseases constantly subdivided in new sub-categories (for ALS there might be dozens of sub-types) is very interesting to the pharmaceutical industry who might sell “precision drugs” that are very costly but it is counter-productive for patients as it further delay the availability of drugs. Having common research on several proteinopathies (such as TDP-43) would be much more in our interest.
* I think the sentence “In the case of ALS, researchers have been able to convert pluripotent stem cells derived from skin/blood into becoming motor neurons” is not accurate, it might have been done in-vitro but that means nothing for pALS.
* In overall I think this site focus on stem cells is wrong. We do not know why motor neurons die, or even if the root cause is motor neuron are dying, so it is a long stretch to assume that infusing other cells in the CNS would magically solve the problem. And stem cells therapies are usually very inefficient, only a few percent of the cells are living for a few months, meaning the healing effect is feeble and do not last (see Nurown).
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Dabmar, I think there is a misunderstanding about this article.
This study is not about making a new treatment but about understanding what are the roadblocks ahead in therapies like Nurown.
In therapies (like Nurown) that use MSCs, they introduce them intrathetically behind the CNS to infuse neurotrophic factors locally (chemicals that helps cells to live).
It is important that those MSCs live well in their new location and are fully working to produce neutrophic factors locally, hence the study about the influence of local conditions such as cytokines.
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> Let’s advocate for responsible, productive research!
I am in, but people think too much of scientific papers. This is well known and had made the matter of several editorials in the prestigious review Nature: Real science is rare, one third of academic papers are just junk and most studies cannot be replicated including famous ones.
There are web sites dedicated to separate the junk from the valuable works: replicationwatch, pubpeer, etc…
Most of the papers that are published did not need much time to be written. Sometimes even only hours (I have been witness to one case). I think this one is of the same league (it is a retrospective study).
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Dear moderator,
1. Did you check if this is not another scam (it seems there are many scammers in healthcare). I can find two links, one to a clinic claiming to apply Bernardo Pinto Coelho diet, and the other to a clinic with roughly the same name (http://www.doutorpintocoelho.pt/a-clinica/).
2. Are there any other credible sources (doctors) that tell that his symptoms improved?
Many thanks
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https://hackaday.io/project/6584-headphone-robot
https://hackaday.io/project/13349-50-foot-controlled-mouse
</span> -
Parkinson is a terrible disease, and the price on carers is high.
There was recently an article in Science about lack of results in terms of effective treatments in humans in Alzheimer research.
The main message was that when people are old, they have many conditions. So any research that try to target something specific will fail to succeed, merely because brain cells die for one reason or another and there are many.
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So this apply only to people with C9orf72 gene with long repeats. I am not sure there are so many people with such mutations. And somehow is it so strange that a highly disrupted genome gives a bad prognosis?
I also wonder how it explain the focality of ALS (it begins in one or two precise places), the progression and the fact the mostly only aging people get it?
If all diseases where explainable with genetics, we should get them at the latest after puberty, like for myopathies or SMA. We begin to biologically aging right after that (for ex. look to thymus involution).
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Henry, I agree completely with what you said. The information about ALS is confusing and conflicting and each case is different.
In the case of my two relatives that had ALS, the neurologists that were consulted (in France, and including an ALS specialist!) did known very little about ALS. Certainly much less that what can be learned by browsing casually on AlsNewsToday.
What complicate things is that there are many pathologies that are very similar to ALS, for example the Wilson disease which is treatable. In the UK they lump all those diseases under the term “Moto Neuron Diseases” which may be very wise. But some diseases like SMA (kind of ALS that strikes infants) are still not included under this umbrella term.
A good list of diseases more or less similar to ALS is on Wikipedia
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Hi David,
In scientific literature most of the time there is the email address of the main author.
They most often kindly answer to honest questions.
Another possibility is to ask people on biology forums what they think about your theory .
Good luck.
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I forgot another important gene in fALS: <i>C9orf72</i>
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Julie,
Only a doctor could provide information about the origin of ALS in your case, and probably only in the case it is a familial ALS.
We have genes in our cells, genes are the blueprint that the cells use to produce proteins. Proteins are the little motors, sensors and messaging system of the life. The cell uses in some cases genes that are not of the standard type (scientists call them “wild type”), so those genes might express proteins that do not behave correctly. There is nothing wrong about that, we all bear multiple mutations. There are ~30 genes involved in ALS but most people with the familial form have either a defective TARDBP gene (95%), SOD1 (5%) of FUS (5%) or a mix of the TARDBP and FUS.
The familial form of ALS does not follow Mendelian inheritance, both parents have to bear at least two defective genes. So children do not automatically inherit fALS.
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I once used the data from the CDC in a back the envelop calculation, it shown that the prevalence of ALS was higher in smaller (maybe rural) counties.
But I am neither a scientist nor living in US, so take it with a grain of salt.
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Hi Pham Ngoc Luu,
From Wikipedia: This gene encodes a member of the beta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization
CA+ receptors have been associated with ALS. There are several theories, the oldest is perhaps the “excitatory” one, but there are other, one recent is about the AMPA receptor.
From Wikipedia again: Excitotoxicity, or nerve cell death caused by high levels of intracellular calcium due to excessive stimulation by the excitatory neurotransmitter glutamate, is a mechanism thought to be common to all forms of ALS. Motor neurons are more sensitive to excitotoxicity than other types of neurons because they have a lower calcium-buffering capacity and a type of glutamate receptor (the AMPA receptor) that is more permeable to calcium. In ALS, there are decreased levels of excitatory amino acid transporter 2 (EAAT2), which is the main transporter that removes glutamate from the synapse; this leads to increased synaptic glutamate levels and excitotoxicity. Riluzole, a drug that modestly prolongs survival in ALS, inhibits glutamate release from pre-synaptic neurons; however, it is unclear if this mechanism is responsible for its therapeutic effect.