A scientist gave acetylleucine to his 90 years old father (postpolio) with balance and cognitive problems

pattismith

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An anecdotal report by an Oxford basic neuroscientist: effects of acetyl-dl-leucine on cognitive function and mobility in the elderly
  • Frances Platt (1)
  • Michael Strupp (2)
  1. Department of Pharmacology, University of Oxford, Oxford UK
  2. Department of Neurology and German Center for Vertigo and Balance Disorders, University Hospital Munich, Munich Germany
Letter to the Editors
First Online: 28 April 2016

Dear Sirs,

F.P.’s father is a 90-year-old retired physician with no signs of dementia. He has experienced progressive postural imbalance for 5 years with no extrapyramidal or cerebellar signs. He has encountered incomplete arousal wakefulness over the past 2 years, but has normal sleep patterns. He had polio in his 20s and has aspects of post-polio syndrome, including partial vocal cord paralysis, muscle weakness and spinal misalignment. He leads an independent active life, reads prolifically and uses a laptop computer to communicate with his family. His only medication was glaucoma eye drops at the time of this study.

Treatment with acetyl-dl-leucine (Tanganil™) was started because the patient was suffering from imbalance and gait disorder, two symptoms reported responsive to Tanganil [1, 2]. He initiated a 1-month course comprising nine 500 mg capsules taken TID with meals, i.e., a total daily dosage of 4.5 g. By 7–10 days of treatment he was more confident walking due to improved...
 
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pattismith

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The full text is available here

What is the most interesting:

"At approximately 2-3 weeks of treatment he suddenly described being fully alert on waking and that his mind had cleared.

His family noticed a significant improvement in his cognitive function, spatial awareness and general demeanor.

He experienced no side effects. After one month he ceased taking acetyl-DL-leucine. His balance remained good for two weeks off medication then deteriorated, where as his cognitive changes gradually declined back to his pre-treatment status over one month. The “get up and go” test was also similar to his pre-treatment performance level. He therefore initiated another month of treatment and found that the improvements he had noticed in the first month of treatment rapidly returned and he now remains on acetyl-DL-leucine at a dose of nine tablets a day taken TID with meals. Despite his initial skepticism, he and his family agree that the acetylDL leucine treatment resulted in significant benefit on multiple neurological systems, in particular mobility and cognitive function, greatly improving his quality of life."


And:

"In a third recent case series in 12 patients with Niemann-Pick type C this agent caused significant improvement of ataxia (7). Interestingly, the parents of three out of these 12 patients also described remarkable behavioral improvement in terms of affect stabilization, improvement of cooperation and ability to act independently in daily life.
This is in line with this short report. Further, a PET study in patients with ataxia of different etiologies given acetyl-DL-leucine demonstrated an increased metabolism in the midbrain and lower brainstem in responders (8), which could explain the benefit on the patient’s mobility."

The quoted PET study is here:

https://www.sciencedirect.com/science/article/abs/pii/S1388245715004228
 
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Wally

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@pattismith - Did you see that one of the researchers (Strupp) noted in the 2017 study linked above may also be involved in additional studies using Aminopyridines and Acetylene-DL-leucine?

See, https://www.ncbi.nlm.nih.gov/pubmed/30182858
Curr Neuropharmacol. 2019;17(1):7-13. doi: 10.2174/1570159X16666180905093535
Aminopyridines and Acetyl-DL-leucine: New Therapies in Cerebellar Disorders.

Kalla R1,2, Strupp M2.
Author information


Abstract
Cerebellar ataxia is a frequent and often disabling syndrome severely impairing motor functioning and quality of life. Patients suffer from reduced mobility, and restricted autonomy, experiencing an even lower quality of life than, e.g., stroke survivors. Aminopyridines have been demonstrated viable for the symptomatic treatment of certain forms of cerebellar ataxia. This article will give an outline of the present pharmacotherapy of different cerebellar disorders. As a current key-therapy for the treatment of downbeat nystagmus 4-aminopyridine (4-AP) is suggested for the treatment of downbeat nystagmus (5-10 mg Twice a day [TID]), a frequent type of persisting nystagmus, due to a compromise of the vestibulo-cerebellum. Studies with animals have demonstrated, that a nonselective blockage of voltage-gated potassium channels (mainly Kv1.5) increases Purkinje- cell (PC) excitability. In episodic ataxia type 2 (EA2), which is frequently caused by mutations of the PQ-calcium channel, the efficacy of 4-AP (5-10 mg TID) has been shown in a randomized controlled trial (RCT). 4-AP was well tolerated in the recommended dosages. 4-AP was also effective in elevating symptoms in cerebellar gait ataxia of different etiologies (2 case series). A new treatment option for cerebellar disease is the amino-acid acetyl-DL-leucine, which has significantly improved cerebellar symptoms in three case series. There are on-going randomized controlled trials for cerebellar ataxia (acetyl-DL-leucine vs placebo; ALCAT), cerebellar gait disorders (SR-form of 4-AP vs placebo; FACEG) and EA2 (sustained-release/SR-form of 4-AP vs acetazolamide vs placebo; EAT2TREAT), which will provide new insights into the pharmacological treatment of cerebellar disorders.
 

Shoshana

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I don't know if the ideas in this post above, is related to either of the 2 issues that came to my mind, or not.

I do plan to attempt to read more of these posts, when I am able, but I am sharing and putting this out here, to see if others have comments related to them.

Acety l-leucine (does not have the "d")
would this be the main or sole ingredient, that was taken by the father written about?

Leucine is part of both:
the BCAA's that many among us have found very helpful, (branch chain amino acids)

and Leucine (one of the essential amino acids) is also included in the Collagen peptides products, that some of us have found helpful.

The BCAA's include 3 particular amino acids, (one of which is Leucine)
whereas the Collagen products include a full range of amino acids, including those and many others.

So, I am wondering if this paper above, is another possible reason to consider trying the BCAA's, and if it might explain why some of us benefit, who have tried them,
Or if it is totally unrelated.

I also wonder about any possible relationship with the fact that some of us MIGHT actually have post-polio, as the man's father knows he does, without us knowing, as many were non-paralytic polio virus strains, not as easily diagnosed (easily mistaken for a common virus and never dx'd or treated at the time we may have been exposed)
and having taken the polio vaccine later on, makes testing for it useless, because we would have the antibodies present , either way.

And for those of us who might have post-polio, undiagnosed, i wonder if it is worth considering trying either Acetyl-l-leucine, which is available OTC, i think, or the Acetyl dl-leucine.
Myself i have many symptoms which overlap with post-polio syndrome, but was unable to absolutely rule it in or out.

Any thoughts or input on any of this, from others of you?
 

Wally

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@pattismith - Thank you for posting this thread. I have never really understood how ataxia (gait, speech etc...) could fit into this illness. I could tell that for me the ataxia does not appear to be progressive, but it definitely worsens with my level of fatigue.

This article published in Medical News Today* in June (2019) was an easier read to help me understand “ataxia”
https://www.medicalnewstoday.com/articles/162368.php
Many conditions and other factors can cause ataxia, including multiple sclerosis (MS), head trauma, excessive alcohol intake, a stroke, cerebral palsy, genetics, and tumors. . . .
Ataxia may also result from certain immunological disorders and infections. . . .If ataxia results from an injury or illness, such as a stroke, symptoms often improve over time and may eventually go away completely. . . .
I also did not realize that cerebral ataxia could result in “difficulty accurately estimating how much time has passed” (as noted in the article linked above), but this is definitely something I have experienced as a symptom of my illness. I also found the reference to gluten being involved in some cases of ataxia to be very interesting. See this article for additional information re gluten ataxia. https://www.medicalnewstoday.com/articles/320730.php

[FONT=ProximaNova, Arnhem, Arial, Helvetica, sans-serif]*(“Medical News Today[/FONT] is a web-based outlet for medical news, targeted at both physicians and the general public. All posted content is available online (>250,000 articles as of January 2014), and the earliest available article dates from May 2003. The site has been owned by Healthline Media since 2016. . . .Healthline Media's website, Healthline.com, is a destination site for health and wellness information, and a competitor to WebMD. . . .[FONT=ProximaNova, Arnhem, Arial, Helvetica, sans-serif]”. [/FONT]See, https://en.m.wikipedia.org/wiki/Medical_News_Today and https://en.m.wikipedia.org/wiki/Healthline)

Edit - Please excuse all the font/text issues in my post. I am using an iPad to type this post and I am having some difficulty with editing.
 

pattismith

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@Wally , thank you for your contribution, I have to look more into this

Myself i have many symptoms which overlap with post-polio syndrome, but was unable to absolutely rule it in or out.

Any thoughts or input on any of this, from others of you?
Shoshana, I'm sorry, I have no idea if taking isoleucine or Leucine or Acetyl L Leucine or Acetyl DL leucine could have similar effects or not.

Whatever the way it works, Acetyl DL Leucine is a cheap and safe drug, so it's worth a try. I started yesterday and will document the trial. I hope I will tolerate it and will be able to keep it at least three weeks to look for the improvement observed by Dr Platt with his father.

acetyl L leucine:
1562787711530.png

acetyl DL leucine:

1562787758323.png
 

pattismith

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Interestingly, about 1.5-2 hours after the intake, I feel abnormal taste in the mouth. This usually indicates that something is modulating my ion channels.

This the way acetylleucine seems to be working:

"The effects of acetyl-DL-leucine on the activity of the medial vestibular nucleus (MVN) and vestibular-related networks were measured electrophysiologically in an UVL guinea pig5. The nature of response depended on the resting membrane potential. Acetyl-dl-leucine acted mainly on abnormally hyperpolarized and/or depolarized MVN neurons, by bringing back their membrane potential towards a mean value of −65 to −60 mV.

Because of this stabilizing effect, acetyl-DL-leucine reduced the asymmetry within the vestibular-related networks caused by the UVL, decreasing the activity of the MVN neurons on the hyperactive intact side and increasing activity on the silent lesioned side, without affecting the neurons with a normal membrane potential.

This mechanism is most likely mediated by its direct interactions with membrane phospholipids such as phosphatidylinositol-4,5-bisphosphate, which influences ion channel activity 6."

http://tay-sachs-sandhoff.de/2018/0...der-wirkweise-von-acetyl-dl-leucine-tanganil/
 

Shoshana

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Interestingly, about 1.5-2 hours after the intake, I feel abnormal taste in the mouth. This usually indicates that something is modulating my ion channels.

This the way acetylleucine seems to be working:
I do not comprehend this post of yours, or the observation regarding ion channels....

Do you mean that it appears a positive or negative result for you?
 

pattismith

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I do not comprehend this post of yours, or the observation regarding ion channels....

Do you mean that it appears a positive or negative result for you?
This is a negative side effect (I get it with medications that modify ion channels activity), but it's manageable.
I also noticed other side effects indicative of nervous system stimulation (muscle tension and pain, lower back pain this morning, sweating, feet movement increased this morning, early awakening.

I probably need to start with a lower dose...
 

Shoshana

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@pattismith
So, a negative side effect, but you think there might still be positive benefit to it, overall?

Please keep us posted. I am interested, both in how you, yourself, is doing, and in this direction of inquiry.

Thank you! Hoping for good things for you.