A glimmer of hope for ALS (amyotrophic lateral sclerosis)?

In Holland we know the poster: “In the meantime I have passed away”, a shocking statement. In order to ask for attention for the terminal illness ALS, the campaign uses expressive faces of people with ALS that have already passed away.

Amyotrophic lateral sclerosis (first described in 1869 by the prominent neurologist Charcot) is a dreadful and rapidly progressive disease causing you to lose muscle function and strength and affects all muscles in the body. This includes the respiratory muscles. There still is no effective treatment for the condition. People generally pass away within a few years.

That’s why the results of an Italian revalidation-clinic on Sardinia are so impressive. Two ALS patients were treated there with the natural anti-inflammatory and pain relieving bodily substance palmitoylethanolamide (PEA), available as the supplement Normast. The positive effects were measurable almost immediately.

Elsewhere in the world ALS patients have started to use PEA. Especially patients with bulbar ASL seem to notice a relatively quick and positive effect.  Our body naturally produces palmitoylethanolamide as a reparation molecule with ALS.

Of course everything is still in its infancy. Patients will often try anything, without guidance of a doctor. The dose should be between 10-30mg per kg of body weight, which is relatively unknown and we suspect many people are using too small a dose to properly decrease the inflammation.

ALS and neuroinflammation

It has become more and more clear over the last years that ALS is an active inflammation of the nervous system, a so-called neuroinflammatory process. [1] [2] These new discoveries have caused substances that can modulate neuroinflammation to suddenly appear as a possible therapy. In 2010, this was described as follows:

“The multiple aspects of the immune response in ALS are beginning to be appreciated, and their potential as pharmacologic targets in neurologic disease is being explored.” [3]

Mast cells play an important role in many cases of inflammation, and activated mast cells have also been found in case of ALS.

“Our data suggest that inflammation in ALS spinal cord and cortex is based on innate immune responses by macrophages and mast cells and adaptive immune responses by T cells.” [4] The overactive mast cell is a factor that can cause problems and palmitoylethanolamide has the ability to calm exactly that cell. The fact that mast cells play an important role in ALS has been mentioned before. [5] Furthermore there is a type of connective tissue, called the glia cells, which can cause damage with ALS due to over activity. [6]

Palmitoylethanolamide for Amyotrophic lateral sclerosis

The clinical observations before and after treatment with palmitoylethanolamide (PEA) were clear. The muscle strength that has severely decreased in the hands, mouth and respiratory system, increased measurably within several weeks, without any negative side effects.

The authors concluded:

Lo studio dimostra che il PEA determina un immediato effetto motorio anche in condizioni di grave ipoamiotrofi a muscolare.

Tale effetto consente di attuare un progetto riabilitativo che, in tempi brevi, determina recupero funzionale accompagnato dalla ricomparsa dei muscoli. 

L’efficacia del trattamento è sicuramente dovuta al fatto che lo stress neuromuscolare causa un processo infiammatorio mediato da cellule non neuronali (mastociti e microglia). L’azione del PEA è quella di modulare l’azione di queste cellule.

Or, palmitoylethanolamide has a quite direct and positive effect on the muscle strength and functionality with Amyotrophic lateral sclerosis. The effects could be caused by the positive effects of palmitoylethanolamide on the non-neural cells, the glia tissue and mast cells.

The last statement has indeed been proven, and there are strong indications that ALS is a chronic inflammation of the nervous system in which mast cells play a certain role. [7] [3] A substance like palmitoylethanolamide can decrease the inflammation stress in the central nervous system. [9] [10] [11]The anti-inflammatory effect of palmitoylethanolamide has been demonstrated by many preclinical and clinical studies, as was recently summarized by the chairman of our foundation.

Every ALS patient can try this supplement, because palmitoylethanolamide has no important side effects.

These observations are not the only ones. On the internet we can see stories of ALS patients who use palmitoylethanolamide and experience benefits, here are some examples:

Case 1: Less fasciculation, better eating and drinking after amyotrophic lateral sclerosis treatment with palmitoylethanolamide

My husband started taking Normast on May 21st and he has had some interesting results. Two days after starting it, he noticed a decrease in Fasciculation. A couple of nights later, he noticed that during the night he was able to move his hand a bit more and his fingers were moving on their own. He said that it was hard for him to explain, but it wasn’t the usual twitching.

Three days ago, I noticed that he was drinking liquids with no choking. That hasn’t happened in quite a while. He is not doing any exercising except walking, as his legs are not affected yet.

I know that the literature on Normast states that it could take up to 50 days to see any pain relief from taking it, so perhaps given a little more time, it might start show positive results for other PALS.

FYI – my husband was diagnosed May 1st, but he has had symptoms for about a year previous. It was probably bulbar onset because we noticed slurred speech first, but we attributed it to some heavy-duty narcotics that he was taking for back pain.

Case 2: Palmitoylethanolamide: easier breathing and less salivating

Ten days of normast (tablets 600 mg x 2) Early May ALS had taken over: my breathing got worse, I needed my Bi-Pap almost 24h/24, I had no more appetite, my voice got weak, my speech was no longer understandable, excess saliva…

PeaPure not only put a hold but I’ve been experiencing some improvements: Breathing: slightly better, I can breathe again 20’ without my Bi-Pap , I eat a little more.

My voice is stronger, my speech is better. Excess saliva: I’ve got a small window in the morning, and another one of around 2 hours in the afternoon during which my saliva is back to normal Arms: a little stronger I now hope that it’s only the beginning. We’ll see. I add some Indian ginseng believing the combination of the two will be more powerful.

Gone with ALS!

The Dutch ALS foundation clearly summarizes it one more time:

ALS (amyotrophic lateral sclerosis) is a very serious muscle/nerve-condition, which causes the nerve cells in the spine and brain to slowly die off. One after the other muscle group stops functioning.

When diagnosed, a person has an average of three more years to live. Little is still known about the cause.

That’s why the ALS foundation is raising funds for research. We are also active in raising awareness about the disease and improving the quality of care for the 500 people that are affected by ALS every year. We have a long way to go before we can cure or slow down ALS. ALS needs to go! Help us to fight ALS.

Palmitoylethanolamide for ALS: administration of PEA

Palmitoylethanolamide could open a new chapter in the treatment of ALS. In our opinion, a test treatment could be considered for every ALS patient, as there are no side effects.

It can be taken as the new PeaPure supplement (400mg capsules containing only pure PEA powder) of as Normast (600mg powder, sweetened with 300mg sorbitol).

Take at least 2400 mg of PEA per day, divided over 2-4 daily doses.

Taking PEA out of the capsule is not necessary, and the sublingual administration is obsolete. Just swallowing is sufficient.

And here is the press release

CAGLIARI, May 10, 2012 – Dr. Simonetta Clemente, Specialist Rehabilitation Center Macon ASL of Nuoro, has experienced a new rehabilitation therapy for Amyotrophic Lateral Sclerosis (ALS), presented in Milan during the second day of the XII Congress National SIRN, the Italian Society of Neurological Rehabilitation.

The SLA, neuro-degenerative disease that affects about one in every 100 (mostly men of middle or advanced age), was treated by the author of the discovery with the PEA – “palmitoylethanolamide” (endogenous compound with antiinflammatory properties cannabinergico effect, discovered years ago by Italian scientists, including Nobel Prize winner Rita Levi Montalcini), with the ‘goal of improving the effects of rehabilitation in these patients, is rendered completely ineffective due to the degeneration of motor neurons and progressive atrophy muscle.

“The study – said Clement – has shown that the PEA determines an immediate motor effect, blocking the progression of the disease, while the patient has a subjective perception of improvement and can do things which before were closed.

This effect allows you to implement a rehabilitation plan that quickly determines the functional recovery, accompanied by the reappearance of the muscles. The cases on which the PEA has been tested only two, but we hope that you can start your research with patients at different stages of severity, experiencing the active ingredient together with a targeted rehabilitation. ” 

 

An addition from ALS community websites: about NGF and its inhibition by palmitoylethanolamide

First a recent reading was rendered about the role of NGF in ALS.

21st International Symposium on ALS/MND – Days 2 & 3 Recap 12/23/2010 By: Robert A. Goldstein Dr. Ferraiculo of the University of Sheffield followed Cleveland at the podium, and focused his talk on describing the role of the lactate shuttle in disease progression. His research showed that impairment of the lactate shuttle at various time points before disease onset could rescue motor neurons. His research led him to the NGF-P75 signaling pathway in astrocytes as a target for therapeutic intervention. Ferraiculo found that in SOD1G93A astrocytes, NGF was overacting by nearly 30% more compared to wild-type astrocytes.

In fact, his research found that pro-NGF levels were twice as high. This led him to design several in vitro experiments in which he co-cultured normal motor neurons with SOD1 astrocytes. What he found was that normal motor neurons express higher levels of P75 in that environment. then looked to correlate his findings to the human population of pALS, and found that P75 is over expressed in SOD1 patients’ spinal cord and NGF is over expressed in the CSF from sporadic ALS patients, although the numbers of pALS used in that analysis was not given (Ferraiuolo et al., 2010).  

Astrocytes may modulate the survival of motor neurons in amyotrophic lateral sclerosis (ALS). We have previously shown that fibroblast growth factor-1 (FGF-1) activates astrocytes to increase secretion of nerve growth factor (NGF). NGF in turn induces apoptosis in co-cultured motor neurons expressing the p75 neurotrophin receptor (p75NTR) by a mechanism involving nitric oxide (NO) and peroxynitrite formation.http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.2006.03742.x/full  

And after that the role of PEA in down regulation of NGF:

Moreover, the results reported in the present study are consistent with a recent study demonstrating that the anti-hyperalgesic action of PEA in a model of neuropathic pain depends, at least in part, on the reduction in NGF up-regulation.

Commentary of an ALS patient:

This is a major finding, in my opinion. It might even be a breakthrough because it explains why ALS targets motor neurons and not sensory neurons. It also explains the amazing results reported by Dr. Simonetta Clemente in her study of the effect of PEA on ALS patients. A reduction of both NGF and inflammation would give motor neurons time to regenerate leading to rapid functional recovery.

 

Dr Clemente responds by letter

The doctor that treated the 2 patients wrote this on a forum in response to questions:

Dr. Clemente:

The protcol I have developed must always be adapted for individual cases. As you know, people with ALS have different mobility problems, the same regions affected, of course, when the disease is not too advanced. Infact, the same Normast should be assumed together with a specific protocol I have developed.

I am in touch with many patients and medical colleagues, which write me and tell me they have already tried and did not have any results. But i can tell you, It does work. there is the trick.

Since we should still check for more certainty, at the moment I can only say that, even for patients and their families, time is always long and tyrant, you must give me to me and to other specialists and researchers, at least couple of months in order to run more and deeper studies. We are already active in this matter, in order to receives approvals and permits, because you know that sometimes doing good you also have the risk of incurring in penalties.

 

Evaluation of PEA for ALS

Because ALS is a serious condition, against which nothing stands a chance, it is a relief that there is a natural substance, without side effects, that can offer some solace.

In many studies, conducted since 1970 on over 4000 patients, PEA proved to be safe and effective for inflammation and pain, there is no reason not to try a test treatment.

Because PEA can easily be taken with other medicine, and the safety has been well documented, it gets a green-orange stoplight. Not entirely green because no placebo controlled study has been conducted on the effects of PEA on ALS. Considering the challenges concerning funding this will probably take years.

References

[1] Fujita K, Izumi Y, Kaji R. | [Inflammatory mechanisms in amyotrophic lateral sclerosis].| Brain Nerve. | 2012 Mar;64(3):273-8.

[2] Li G, Esiri MM, Ansorge O, DeLuca GC. | Concurrent multiple sclerosis and amyotrophic lateral sclerosis: where inflammation and neurodegeneration meet? | J Neuroinflammation.| 2012 Jan 24;9:20. doi: 10.1186/1742-2094-9-20.

[3] Calvo A, Moglia C, Balma M, Chiò A. | Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? | CNS Neurol Disord Drug Targets. | 2010 Jul;9(3):325-30.

[4] Graves MC, Fiala M, Dinglasan LA, Liu NQ, Sayre J, Chiappelli F, van Kooten C, Vinters HV. | Inflammation in amyotrophic lateral sclerosis spinal cord and brain is mediated by activated macrophages, mast cells and T cells. | Amyotroph Lateral Scler Other Motor Neuron Disord. | 2004 Dec;5(4):213-9.

[5] Purcell WM, Westgate C, Atterwill CK. | Rat brain mast cells: an in vitro paradigm for assessing the toxic effects of neurotropic therapeutics. | Neurotoxicology. | 1996 Fall-Winter;17(3-4):845-50.

[6] Lewis CA, Manning J, Rossi F, Krieger C. | The Neuroinflammatory Response in ALS: The Roles of Microglia and T Cells. | Neurol Res Int. | 2012;2012:803701. doi: 10.1155/2012/803701. Epub 2012 May 15.

[7] Fiala M, Chattopadhay M, La Cava A, Tse E, Liu G, Lourenco E, Eskin A, Liu PT, Magpantay L, Tse S, Mahanian M, Weitzman R, Tong J, Nguyen C, Cho T, Koo P, Sayre J, Martinez-Maza O, Rosenthal MJ, Wiedau-Pazos M. | IL-17A is increased in the serum and in spinal cord CD8 and mast cells of ALS patients. | J Neuroinflammation. | 2010 Nov 9;7:76. doi: 10.1186/1742-2094-7-76.

[8] Calvo A, Moglia C, Balma M, Chiò A. | Involvement of immune response in the pathogenesis of amyotrophic lateral sclerosis: a therapeutic opportunity? | CNS Neurol Disord Drug Targets. | 2010 Jul;9(3):325-30.

[9] Pacher P, Mackie K. | Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.| J Mol Med (Berl). | 2012 Apr;90(4):347-51. doi: 10.1007/s00109-012-0884-1.

[10] Moreno-Martet M, Mestre L, Loría F, Guaza C, Fernández-Ruiz J, de Lago E. |Identification of receptors and enzymes for endocannabinoids in NSC-34 cells: relevance for in vitro studies with cannabinoids in motor neuron diseases. | Neurosci Lett. | 2012 Feb 6;508(2):67-72. doi: 10.1016/j.neulet.2011.12.020. Epub 2011 Dec 22.

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