jean-pierre-le-rouzic
Forum Replies Created
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I wonder if there are accompanying lesions, like in lichen planus, a chronic inflammatory condition?
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> My right arm and bicep have hurt plus swollen before officially diagnosed
It looks like inflammation?
> but never explored as upper motor neurons are only responding on EMG?
What do you mean? EMG is about detecting skin surface electric activity of muscles. So IMO inferring status of lower and especially motor neurons is as reliable as doing astrology.
Did you take a second piece of advice, from a rheumatologist as your right arm and bicep hurt and swell?
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I completely agree with the previous comments:
– Nutrition is for me the most important aspect as ALS patients need more calories and protein intake than healthy people as shown by Kasarskis and al. in 2014. Plus half of ALS patients have insulin resistance as Alzheimer patients, it can’t be a random coincidence.
– Muscle wasting is nearly ignored by research (~6% of publications) while this is the characteristics which gave its name to ALS (Amyotrophic Sclerosis). I guess that the cellular response to stress plays an important part here.
– An extension of previous point is that I feel that it hurts research to present ALS as a “Motor Neuron Disease”. Many nerve and cellular studies tell that ALS strikes all the body, but if you are a young scientist it is unwise to take this career path, only scientists in sports or nutrition do that kind of studies without career risks, for others it is frown upon because you know “ALS is a Motor Neuron Disease”.
– There is nearly no research on managing the disease, for example in stroke patients there use Pacemakers to stimulate the laryngeal reflex.Currently I am preparing a large revision of my book on the state of ALS research. It will elaborate on two points:
* One is the failure (Arimoclomol and Biogen/Ionis genetic therapies) or relative success (AMX0035) of recent drugs trials and what it teaches.
* What is NOT studied in ALS research.Jean-Pierre
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The business actors in the field of drugs are much more diverse than “companies”.
– Investors are making long term financial bets, one on five success and they would be satisfied. They are prey for biotechs. Investors do not need patents.– Biotechs are bets on one or several drugs on which they have IP, i.e. patents. God knows where they find there drugs, but it’s not from basic research. They seek money from investors and hope to have some success, in order to sell themselves to a big company. Biotechs are not the cleanest industry, they buy well known voices like Nobel scientists and even when they fail, they pretend that “on a subset on patients, a statistically strong signal that survival had improved up to 10 months”. It’s well known also that when they meet a failed clinical trial, instead of searching for a better drug, they search to apply their drug on another disease. They need patents, but just because it is a proof they have some assets.
– Universities. They do basic research, they have the goal to teach students, not to heal patients. Sometimes they ask for patents, which their IP department hope to sell to a big company. This never happen, at best it’s a poor biotech which buy a license to the patent, but it’s rare as biotechs are popping in existence from thin air.
– Big companies. They are the fat cats. They either search for low hanging fruits, or to buy either a license to a patent or even a biotech but only if a clinical trial is successful. Sometime they wait for the interesting biotech to go bankrupt. It’s cheaper than buy on successful one. They care much for patents.
So in summary research and patents are disconnected domains.
(I was granted 12 patents)
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> I have been told multiple times by a Neuromuscular specialist that MND are painless.
The two people in my family who had ALS did not complain of pain, but maybe that still had pain.
I think neurologists tell that ALS is painless because the current definition of MND is (obviously) about dysfunctional motor neurons.
My personal opinion is this is just a century old myth: TDP-43 mislocated, misfolded proteins which are present in 95% of sporadic ALS are found in many places in the body.
Plus MRI shows that anomalies in many parts of the brain and spine, not simply in the motor area as the definition of ALS, or the very name of MND imply.
Last: There are many studies discussing ALS starting at the interface between the nerve and the muscle it activates (the neuromuscular junction) and then spreading. This matches well the experience of many patients who had first a “small problem” with one dropping foot or a thumb loosing strength and ulnar muscle mass.
If this is true, most ALS cases are not motor neuron diseases but something like a distal axonopathy. Search for “ALS dying back hypothesis”
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It seems to me that “Target ALS” is one of the few ALS organizations that does not claim any intellectual property over the research it funds.
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> He clearly had not heard of bulbar-onset
> The EMG is a faulty test, only as good as the provider. I can’t recall the precise article.
It could be for example:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596501/Where they tell:
Nonetheless, not all neurologists correctly diagnosed ALS patients at first evaluation (55%), even if an EMG was requested (75%). Although not systematically investigated, the most common alternative diagnosis in the EMG report was severe root lesion and spinal stenosis, in particular for patients with LL onset and preserved UL, bulbar, and respiratory function.
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Hi NJGuy,
> a drug Aduhelm which is a new drug for Alzheimer and it addresses the same issue of dissolving amyloid in brain. Can this not be used for treating pALS?
As far I understand it, it is not the same issue. Nobody knows the cause of Alzheimer’s disease and there are two main competing hypotheses:
– It’s a buildup of extracellular amyloid plaques
– It’s an intracellular buildup of Tau protein.In ALS there is a buildup of intracellular TDP-43
That said it’s an extreme simplification as there are many other proteins involved in both diseases.
Yet it seems that many scientists and biotechs are working on antibodies or intrabodies (a smaller version of antibodies), so I expect to see good news on the clinical side soon.
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> Has anybody thought of Chemotherapy?
This is the thread of people playing with fire? 😉It seems to me that the challenge in ALS is to keep nerves cells (CNS + PNS) alive as long as possible.
Chemotherapy has a strong effect on cells like astrocytes (it kills them) without which neurons die. This has even a name “the chemofog”. Look at Wikipedia, there is detailed article on it. It looks to me it’s the last thing an ALS patient would need.
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> immunosuppressant drugs … under some doctor’s observation
Immunology is thought as one of the most complex domains in medicine.
Few specialists/scientists pretend to understand it in the healthy human, so I guess it’s above the head of the average practitioner to apply its knowledge of immunity to ALS.
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> C9ORF72 study was rejected by the ethics commission in Germany.
Which study?
Do you have a link or a clinical trial number?Otherwise my feeling is that a quiet life, without drugs/alcohol/intense sports with good organic food and a good diet (pALS need much more energy while they are still able to move), is probably something which makes sense.
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> I ask are Biogem going to continue the monthly doses of Tofersen just a yes or no answer please
Sorry I have no special information other than what was posted in Biogen and Ionis’ public statement.
However they say: “Given the high unmet medical need, Biogen will expand its ongoing early access program (EAP) to the broader SOD1-ALS population”
media.biogen.com/news-releases/news-release-details/biogen-announces-topline-results-tofersen-phase-3-study-and-its -
The results are disappointing to say the least.
You can find my (angry) analysis on my blog:
padiracinnovation.org/News/2021/10/disappointing-results-from-the-valor-study-on-tofersen-biib067 -
> My family must have a mystery gene.
Then it’s a pity nobody is studying your family.The C9orf72 was a real mystery, while it causes half of the cases of familial ALS, it was found only in 2011, 18 years after SOD1 mutations were associated with ALS.
The reason it eluded researchers is that for them a genetic disease could only stem from a gene … and C9orf72 mutations were not on a gene but on something weird, that was thought as having no usefulness: A repeat expansion (HRE) in the non-coding region of C9orf72.
“Non-coding” means that that portion of ADN is not used to produce ARN, the blueprint that ribosomes will use to make unfolded proteins (that will be folded in the ER).
This is because since Crick and Watson nearly 50 years ago, every scientist is taught about the “biology central dogma’. It teaches that every genetic trait is caused by ADN.
Scientists know this is untrue since the 1970′ (see “epigenetics”) , there are even ALS drugs targeting epigenetics, like APB-102 from Apic Bio. Even the well known ASOs from Biogen for SOD1 and C9orf72 does not alter DNA, yet alter protein production.
However, the “central dogma” is still taught without being amended, epigenetics is still a dirty word for biologists. Leading to semantic aberrations such are denoting C9orf72 mutations in ALS as bing mutations on the C9orf72 gene.Other scientists created the notion of “RNA genes” for the effects of non-coding genes, even if the notion of a “RNA gene” is meaningless.
Unfortunately we are living in the prehistory of medicine and biology.
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Thanks Beth!
I found with some difficulty literature about this trial, it seems there were many unwanted side effects including severe weight loss (one of the worst things to inflict on an ALS patient) and severe cough. And as you said the primary and secondary goals were not met.
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Hi Beth,
Please could you share which drug trial it was?
Thanks!
Jean-Pierre
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Yes indeed.
This publication states 56% of people with ALS experience pain:doi: 10.3390/jcm11040944.
Pain-Related Coping Behavior in ALS:
The Interplay between Maladaptive Coping, the Patient’s Affective State and Pain
Ina Schlichte, Susanne Petri, Reinhard Dengler, Thomas Meyer, Aiden Haghikia, Stefan Vielhaber, Susanne Vogtpubmed.ncbi.nlm.nih.gov/35207215/
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I am not sure why ALS specialists would make such a blanket statement as “ALS is a painless condition”
Because it’s supposed to be a disease affecting only motor neurons. Motor neurons do not convey sensory information at all, that’s the specific function of sensory neurons.
Motor neurons send information from the motor areas in the brain to the muscles while sensory neurons send information from their extremities to the brain.Yet for me there is something weird in the statement that ALS affects only motor neurons, because in a PNS nerve there are both motor and sensory neurons, even in the corticospinal or corticobulbar tract there are sensory neurons (~40%).
Given this close proximity, how could a neuron disease affect only one type of neuron and not others? Something similar was already argued by scientists but I can’t remember the reference.
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It’s a beautiful writing, Duanne.
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> This link tells that a new clinical trial is starting, it does not tell it is stopped?
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> saw the cholesterol on border line and he told me to be careful
How strange, cholesterol constitutes a large share of brain’s chemicals, as cholesterol is an essential lipid component of myelin.
Moreover cholesterol synthesis decreases with age. -
> They advised against taking many supplements because they suppress appetite
Thanks for the information, I didn’t know that. It’s very important indeed.
Losing appetite is perhaps the worst thing that could happen to pALS, because they need more calories than a healthy person (at least when mobility is not lost) -
Many thanks Mark!
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> I like what ALS Assoc did here with the screening tool in trying to speed up dx.
Yet, it’s a bit weird that an ALS association tries to define ALS.
The ALS association can steer the direction in which research goes, simply because they fund a lot of it.
It has zero interest to fund research that would find that ALS is actually either or both:
– A spectrum of different diseases (different etiologies) that have motor issues and muscle wasting as outcome.
– A spectrum of diseases that stem from a common generic root, like most proteopathies hint at or even more audacious like that those misfolded proteins are the consequence, not the cause of those diseases. So approaches to reduce proteins level (like in most ASO approaches) are useless.