I wonder if there are accompanying lesions, like in lichen planus, a chronic inflammatory condition?

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.

Hi Beth,

Please could you share which drug trial it was?

Thanks!

Jean-Pierre

> 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… Read more

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… Read more

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… Read more

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,… Read more

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… Read more

> 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… Read more

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.

A few years ago there was a phase II of Guanabenz in Italy. Guanabenz is a drug used to treat hypertension.
The results indicated that this drug was roughly as effective as AMX0035 from Amylyx.
Yet at the dose tested, this drug was unsafe on the long term so a new version was designed: Sephin 1.
This new drug will be tested in a few months… Read more

It’s a beautiful writing, Duanne.

> 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…

Read more

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… Read more

> 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 dies. This has even a name “the chemofog”. Look… Read more

> immunosuppressant drugs … under some doctor’s observation
Immunology is thought as one of the most complex domains in medicine.

On other forums there are stories of some people who succeeded partially with similar/opposite (IVIG) approaches, but I guess they were misdiagnosed. There are also stories of people who tried and failed to… Read more

> This link tells that a new clinical trial is starting, it does not tell it is stopped?

> 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.

> 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.

> 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… Read more

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

> 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!

> 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… Read more

> 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… Read more

A 12-week phase I dose-escalation trial open label has been launched in early 2021 in Japan to evaluate the safety and tolerability of Bosutinib.

The results of this clinical trial had just been announced.

Of the nine patients who drank 100-300 milligrams of bosutinib daily for 12 weeks, five stopped progressing, the remaining four… Read more

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 🙂

> 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.

The ability to generate in-vivo spinal cord motor neurons from human pluripotent stem cells would be a major milestone in motor neuron-based diseases such as ALS.

Indeed we are still decades away from that goal. Nevertheless scientists are working hard toward that goal.

Motor neurons are involved in governing voluntary actions and in… Read more

> 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.

> 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… Read more

> 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… Read more

> 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… Read more

> 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… Read more

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… Read more

Thanks Andrew,

> open access arrangement may be started next year prioritising more rapidly progressing patients.

It’s a nice information!

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.

Many thanks for the answer Les!
First person in UK, possibly in Europe? This is very impressive!

In March 2019, Biogen added a Phase 3 efficacy arm to the same trial. Called VALOR, the study enrolled 178 people with SOD1-ALS, who received an undisclosed, fixed dose of BIIB067 or placebo for 28 weeks.

The trial was conducted at 31 sites in North America, Europe, Australia, and Japan, and finish in July 2021.

Currently there is no news… Read more

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.

> 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.

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

> 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… Read more

Thanks Mark, that’s wise words.

> 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… Read more

> 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… Read more

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.

A recent public relation article was been widely shared on the internet.
It tells that:
“Our results … suggest that defects in cholesterol metabolism may contribute to ALS and FTD, as well as other neurodegenerative diseases characterized by TDP-43 aggregates,”
I analyzed the scientific article that’s behind these claims and … Read more