Jean-Pierre Le Rouzic
Forum Replies Created
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> I set up the lumbar puncture (Intrathecal)
I am not a religious person, nor proficient in English, but I thank you for your dedication to the search for an ALS cure. -
> They may be withheld by customs.
TUDCA is not a regulated drug, it’s a supplement.
Yet you might have to pay VAT in addition to the Amazon public price. -
> And what could that mean for me? I have C9 ORF72
Jörg,
Some caveats:
Nobody knows how to heal from ALS, the article above is a research article, basically it hints that something is wrong in insulin management in a fly model of ALS.
Flies are insects, they do not even have a spine like vertebrates, scientists use them as they are convenient and low cost. Basically scientists who use flies are like people looking for they lost keys under a street light, because there is light only under this lamp post.Yet this article is yet another one that indicates that insulin resistance in some patient is a consequence of their ALS.
Going further is only speculation. Let’s dive:
My opinion is that ALS is not really a genetic disease: As people get it at an older age. If it was really a genetic disease like SMA (another motor neuron disease) or Phenylketonuria people would get it as toddler.
My opinion is that the genetic variants on the human genome like SOD1, FUS or C9orf72 mutations, are only like a constant burden on cells. Scientists call that burden “a cellular stress” (Zelluläre Stressreaktion).There is a mechanism called cellular stress response, it’s a coping mechanism. But unfortunately it’s not something as elaborate as the immune system, it’s a basic cellular mechanism that was inherited from our primordial ancestors billion years ago. What it does is that nearly stop all cellular activities in order to enable to endure the stressing event. Think of fungi that become spores and that able to survive thousands of years, before returning to life when conditions have improved. It’s something akin.
Indeed a cell under cellular stress response cannot not function properly. I think that explains ALS symptoms at least at an early state like failing members. There is a dark side to this coping mechanism: Indeed when the stress is prolonged, the cell dies.
I believe this is what happens in ALS later stage.
What can one do before waiting for a therapy?
It’s odd, but having a BMI at 27 helps people to survive. This had been proven many times. There are even online calorie calculators for pALS, as they need ingesting much more calories than healthy people.
Some scientists think that changing the diet for a lipid metabolism, could help but that still controversial.
ALS people who have a PEG live much longer than those who do not.
And indeed having an healthy life style, no alcohol, etc.Let’s keep our fingers crossed.
Jean-Pierre
(English is not my native tongue) -
Many thanks for the answer Les!
First person in UK, possibly in Europe? This is very impressive! -
Hi, my blog is about news from research in neurodegenerative diseases.
https://padiracinnovation.org/News/ALS is special for me as two people in my family died of ALS.
There are also a calorie calculator for pALS and a biomarker page to predict (and manage?) progression.
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Thanks Richard,
The status of Masitinib study has evolved since yesterday.
It was previously stopped in June and it resumed yesterday, at least for Europe.JP
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> so then I looked into the als drug amx0035 found out it was made of two drugs one cost $500 and ounce and the other Tudca i ordered from amazon
At my job, patent officers often said us that it is impossible to patent an existing product for two reasons:
1. A patent is about a process (akin to a recipe), not about a new usage.
2. A patent is about something new, so it is impossible to patent something that exists already.But they added that it was possible to patent a combination of two existing products, at the condition it is a novel, never described combination.
So the patent is written as:
This patent describes the combination of two products, such and such, with an application in this domain -
Thanks Mark, that’s wise words.
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> In case the NY Times link doesn’t work for you (you’ll need to subscribe to open it)
If you reload the page then immediately stop the reload you can read the full page.
There are several alternative means to bypass such paywalls. One for geeks is to drive the website to think that your browser’s request is from a search engine, as most sites under paywall must still authorize search engines to index their content (if they don’t, their precious content can’t be indexed on Google and would loose any value).
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> If I turn my palm up I can do it. This makes no sense from the nerves in arm/hand perspective.
Intriguing! I guess that it makes no sense if we think of nerves as electrical conductor between the brain and the muscle. Here is a random speculation:However it’s a bit more complicated. When we make a movement, the primary motor area in the brain has no notion of which muscle must be activated. It’s more like the “intention” to make a movement. The actual activation of muscles is done by lower motor neurons, and in some cases, the interneurons which are linking upper to lower motor neurons inside each vertebrae. The interneurons are for example involved in repetitive movements.
So what “may” (I am nor a scientist/doctor) is that in the motor area of your brain, there are some upper motor neuron bodies which are dysfunctional while other upper motor neurons are still able to evoke stretching your finger. The only difference between the former and later upper motor neurons is perhaps that the latter are activated when your palm is upward.
If I am correct, you are right to develop exercise to “see” if you can get back the function. The brain is malleable and as long as the lower motor neurons are healthy, it may work.
Good luck!
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Thanks for the link, Richard, but it’s a work done in-vitro and for a mutation (VCP) that represents ~0.3% of all cases.
The odds that it could be useful for the average pALS are near zero. -
> There are 4 or 5 clinics offering Stem Cell therapy also in India. They do not divulge any positive outcomes to the therapy.
In India as elsewhere, there have been official warnings about “stem cell clinics”.
Stem cells aroused a huge craze a few decades ago, it was seen as a solution to all problems. But in the end it didn’t solve anything at all.
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I think that a very important step has been achieved in understanding the mechanism of how misfolded TDP-43 aggregates in cells.
This is important as misfolded TDP-43 aggregates has been identified since 2006 by Virginia Lee has one of the most common pathological feature in all forms of ALS (> 97%), half of FLD dementia as well as a quarter of Alzheimer cases and a significant number Parkinson cases. Indeed TDP-43 proteopathy mirrors other well known proteopathies that are found in Alzheimer or Parkinson diseases.
Scientists in India found that acidification, a process which happens in aging and which results from metabolism (hence my post in this thread), results in TDP-43 misfolding.
I blogged about it today on my web site padiracinnovation.org.
Indeed it’s only my own opinion that it’s important, but it’s well known that I am not someone who react very enthusiastically to most publications about neurodegenerative diseases.
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Bonjour David,
Votre français est excellent!
J’ai toujours aimé l’anglais, mais l’école ne m’a pas beaucoup aidé à ce propos. Par contre l’attrait pour la science-fiction et l’activité professionnelle m’ont permis de m’améliorer en anglais. Mais l’anglais parlé en écosse me semble absolument insurmontable 🙂 -
> Hab von Anfang an, die Diagnose in frage gestellt.
People with Parkinson disease have also severe constipation, and C9orf72 is also found in some people with Parkinson.
All these diseases (ALS, Alzheimer, Parkinson, FTD, Huntington, etc are not clear cut as in textbooks, each case is somewhere in a spectrum of diseases. One scientific article says that it’s common to have up to four comorbidities in people having ALS.
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> Was ist GI Funktion???
Gastro-Intestinal
(Magen-Darmtrakt) -
In German’s Amazon there are two brands of TUDCA.
In Netherland’s Amazon there is one brand: “TUDCA Liver Support” -
I guess this clinical study is more credible than many other.
Yet from a publication [0] it looks like Nurown’s therapy.
It’s reinjected MSCs that are “expected” to produce Vegf, a neurotrophic factor.
There were two dozen unsuccessful Mesenchymal clinical trials in ALS, why do they expect this one to be successful?
Another thing is a bit strange is that it looks like that there was no pre-clinical trial, they jumped from in-vitro experiments to clinical trials!
Other companies could find this as unfair competition distortion.[0] ncbi.nlm.nih.gov/labs/pmc/articles/PMC7977179/
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> Anova-IRM in Offenbach, Germany seems to offer stem cell therapy
In Germany you can find private clinics that offers (against huge amounts of money) treatments against cancer, diabetes, ALS, Alzheimer. All kind of diseases that are not treatable in the rest of the world. Indeed they are just scams that happen to be (more or less) legal in Germany.From a German point of view, these companies are just companies that have to be registered as a sole proprietorship, that’s all. There is no additional requirements in the area of healthcare. Their doctors can even be naturopathe doctors without classical training.
From the perspective of USA/Japan/Rest_of_EU these clinics would probably be illegal.
Please not that this clinic is not even registered as providing stem cell therapies: It is registered as “Specialist in diagnostic radiology and physicist”
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I nearly completely agree Mark, except the bit about biomarkers.
We have a good biomarker, it is TDP-43 aggregates in cell’s cytosol, it appears in 97% of ALS cases, it could even be detected in the blood stream.Why is it not used? Perhaps because it does not fit the narrative about this disease that scientists expect. TDP-43 aggregates are not specific to upper motor neurons, it indicates a systemic problem.
Plus most actual cases of neurodegenerative diseases have a mix of proteopathies, the patients have perhaps mainly ALS, but also proteopathies such as what is found in Parkinson, FTD, Alzheimer, etc. Neuros with their beloved EMG test can’t detect that.
So much for the clear textbook definition of ALS as mainly a disease of upper motor neurons as described above.
Max Plank famously said that science progresses one funeral at the time. Do we have to wait for a new generation of scientists to discover effective drugs?
Perhaps not, there is now a flurry of activity on TDP-43, for example Promis Neuroscience made news about it few days ago.
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Thanks Andrew,
> open access arrangement may be started next year prioritising more rapidly progressing patients.
It’s a nice information!
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Yes, thanks Amanda,
The link tells “The study completed on 15 Jul 2021” and that there are no posted results.
I can’t find any news on internet. -
> What is the NHS?
Given that David is a UK citizen, I guess it is the National Health Service. The publicly funded healthcare system in UK.
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Dr. Rothstein works in ALS research since a long time (~20 years?). But what is presented here is not very impressive. Working with iPSC-derived is something that could be done at little cost now, and (fortunately) many teams are working on ways to mitigate TDP-43 aggregates.
And it only pushes the goal post further away: What makes CHMP7 aggregate in the nucleus?I guess this work has two objectives:
1. Participating in the run to patent TDP-43 therapies.
2. Showing to funding parties that the lab is doing something with their money.