MSA with Ambroxol HCL - a tentative success story!

[Robb48]

Final edit update! Writing this 13/2/23. While our success with early ambroxol looked positive, her disease progression continued. At this point my guess is that it affects downstream symptoms, but only clinical trials will be able to say if it slows progression. Also, although it did greatly improve her quality of life for a while, I suspect there was some reduction in scale of those positive effects over time, or perhaps her underlying condition simply worsened to make it look that way.

Aside, she is currently undergoing FMT treatments and we are seeing positive results from that, it looks very hopeful, though it has not been an easy process and we have had some unfortunate complications to deal with. I intend to write a full post about this at some point in the next couple of months, so if you are reading this at some point in the future then check my post history! And good luck!!

-------

Original post:

I'm a little hesitant to post this, as it is still VERY early days, but if there is any chance that what I am seeing is caused by ambroxol, and if it might be replicated by other people, then I think I have a moral duty to put it out and give people the option to test for themselves, or their loved ones.

So, MSA is a rare form of Parkinsonism, very nasty, with an average time to death of around 8 years - or less in the case of older individuals, such as my mother who is almost 70. Very hard to diagnose with certainty, confirmation is often only via autopsy. Which brings me to my first caveat - my mother has a number of atypical symptoms, although MSA can cause a spectrum of effects and the neuro specialists do believe it to be the most likely diagnoses. Still, it is perhaps a note of caution for others with MSA.

That said, I (her son) have been slowly ramping up the dose in accordance with the only official study for Parkinsons, right now she is only a few days into week 3 and on a dose of 180mg x3 per day, taken with food. And this is another reason why I'm so tentative, she's not been taking it that long, yet her condition was improving even after just a few days. I really didnt believe it could be ambroxol at first, because my understanding was that it would take months before benefits were seen. However, the improvements have been (mostly) steady and consistent, and I'm struggling to think of anything else that could cause it. I did previous ramp up her dose of ubiquinol (co-q10) to 900mg, and increase her high dose thiamine to 7g/day from 5g and later 6g/day, but that was weeks prior to starting ambroxol, and I doubt these could cause such a significant improvement.

OK so all those caveats out the way! Her symptoms. A month ago, I would often only get a dozen words or so out of her a day. It was looking extremely bleak. She was socially very disconnected from us, barely taking part in conversations, and her voice was a constant near whisper. She was unable to take part in activities, feeling a sort of sickness or unwellness almost constantly - she couldnt describe it, just said she felt "horrible" all the time, and it seemed to be related to her gut. She might read for a bit, but after a while it would make her feel sick. Even excluding those feelings, her drive was entirely gone. Reduced to watching TV most the day, except for the Herculean efforts of my father to make sure she was getting out for walks daily. Her balance was bad (lots of furniture walking), physically weak, needing help getting out of chairs, and her condition was rapidly deteriorating - faster than MSA should, we thought. For someone who was constantly doing things before, always sorting out the house, cooking, cleaning, finding activities, socially engaged, and maintaining an extremely active lifestyle for someone her age, this was heart breaking. All of these symptoms have decreased, she it now taking part in conversations, engaging with us, being self directed, genuinely SMILING without it being forced, her voice is louder, she is moving easier - not just on her daily walks, but getting out of chairs, cars etc. The differences are striking. However, she also had insomnia before, although intermittent. And that has not improved so far, if anything it is worst, though given how badly it fluctuated before we cannot say with any certainty it is related to ambroxol, and insomnia was not a noted side effect in the ambroxol / Parkinsons safety study. And she is still having occasional bad days in terms of feeling "terrible", but I would not say worst than before, it is rarer and it comes back mostly in relation to when she's had especially bad sleep for a few days. But even when she is feeling rough, the psychological differences are still there, if maybe a little diminished at times - she's still engaging, actively doing things (self-directed), her facial expressions are normalising, more eye contact, voice louder etc. It is hard to say how much better she is in % terms, comparing her now to prior to onset a couple of years ago, but perhaps up to 50%?! At least in terms of her character, psychology, social interactions etc - brain stuff relating to the dopamine systems I guess, her physical issues are improving more slowly. Which seems bizarre from a physiological point of view, since the dopamine (DaT?) scan of the brain showed significantly reduced dopamine uptake, which I presumed meant damaged. So, are they better now?! Were they just "gummed up" before, but the effects on her musculature/mitochondria are more difficult to improve?! We really understand so little about these conditions, but hey, results are results!

Aside, I also have the recently discussed fancy probiotic PS128 incoming from Singapore (both Active and Mind options, will test each), which I am very much looking forward to trying on her given how her symptoms started with and seem to be heavily related to the gut. I'll update on this thread, for good or bad, in coming weeks or months re ambroxol, and note if PS128 does anything.

So! Thats my story. Honestly just writing this is bringing me to tears, I cannot believe I am saying it but if progress continues, could it even lead to a "cure"?! If only partial..... with a condition that is so horrible, and previously so unstoppable... well.... Of course without proper clinical trials there is no way to know if this is truly the ambroxol, or if what we are seeing is in any way reproducible, and who knows -her condition could nose dive again tomorrow, or progress might simply stop..... but.... now there is reason for hope. My heart goes out to anyone else suffering from this brutal condition, or with relatives who are suffering. I wish you all the best of luck!

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Addendum - 17 tumultuous days later! Soon after writing the above, I stopped my Mum on her regimen of other supplements, because we ran out and I wasnt sure if she needed them any more. This turned out to be a bad bad horrible terrible decision, and she tumbled back to her old state over a period of a few days. I then bought more and tried to re-start her on them, but there were issues with the dosing of thiamine that complicated things further. However.....she now seems to be back on track. So, a few additional thoughts:

- The repeatability of the improvements we have seen may depend on the other supplements she is taking in combination. They seem to work together, or affect different systems in complimentary ways. I now have her on just 2g/day of thiamine, and a strong b-complex (solgar 100) to assist after reading more reports from Dr Lonsdale etc. In addition to the 900mg/day of ubiquinol, reishi, lions mane, and now 200mg x 3/day of ambroxol. However, to re-iterate what I said above, I had her on these supplements prior to ambroxol, and we didnt see anything like these effects. So, well, they seem to work together, at least for her! Ambroxol dose, I kept her on the same while going through the above complications, not wanting to complicate further, just moved from 180 to 200mg yesterday, will look to increase properly again in the coming weeks.

- Previously when writing above, I had her on up to 7g/day thiamine, as from the Q&A with Dr Costantini he mentioned that HDT works also with MSA, but that higher doses are required (4-6g/day being his stated upper dose for Parkinsons). And while I only very gently took my Mum up to this dose, unfortunately that also meant I didnt realise it was causing other unpleasant side effects, and I now believe her insomnia was caused/worsened by too much thiamine. Although this is something she suffered from before I started her on HDT, there seems to be a correct dose that assists sleep, but above which it worsens a range of symptoms in unpredictable ways. Right now she's sleeping well, her condition is improving, she is become more sociable again, etc etc. So, fingers crossed, but looking good....!!!

Been a crazy couple of weeks, and I have only myself to blame - turns out you should never hard stop powerful medicines, and thiamine in these dose ranges really is medicine. But finally now starting to breathe a sigh of relief!

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Addendum #2 on 20/12/21: Tests have confirmed a diagnosis of MSA-P. In terms of her condition, much as I reported above, her interactions with us are still good, at times almost normal, and she is self-directing sometimes to do jobs around the house. However any improvements in her physical symptoms - balance, stamina, strength - have been less noticeable. Some improvement perhaps but definitely not as significant. Early days with PS-128 probiotic, unsure if any effect, possibly, will hopefully be trying spermidine to enhance autophagy next. Docs want to sign her up to exenatide trial.

[park_bear]

Awesome! Thanks for sharing! Keep us posted!

[faridaro]

Quite amazing and encouraging. Hope the improvements will continue and we'll hear more good news!

[chartist]

Robb,

Your mom is very fortunate to have you as her advocate! These results must be very uplifting for both of you!

I hope your PS-128 test goes as well or better than your Ambroxol test! I look forward to your updates. These kind of results for MSA seem incredible! Thank you for this update!

Art

[Farooqji]

thanks for sharing. Hope the improvements continue. Keep us posted

[Zella23]

Positive results, well done for trying to help your mother with this condition, please keep us updated and I wish her well with her recovery. Well done for trying other alternatives which seem to help many sufferers.

[Dragona]

Wonderful very inspiring

[Millbrook]

Hi Robb48,

I understand perfectly when you say writing about this brings tears.

That was how I felt about PS 128- how a simple probiotic can bring about so much change.

1 Corinthians 1:27 KJV

[27] But God hath chosen the foolish things of the world to confound the wise; and God hath chosen the weak things of the world to confound the things which are mighty;

So happy for you that ambroxol is the light that shines so bright for you. Another member also shared about the great improvements experienced with ambroxol. Hope that PS 128 can bring about even more normal functions.

Your mother is so blessed to have a son who is so engaged in promoting her well being.

Wishing you continued improvements

[Robb48 in reply to Millbrook]

Great quote, thanks! I'm so grateful for you and all the other people on this forum who are contributing, none of this would be possible without an engaged and driven community. I've always had a lot of faith in crowdsourced info, happy it is paying off! Myself, I cannot imagine doing anything other than throwing my all into trying to help her, there is no alternative.

[Marie1895]

Wow, that is wonderful and gives many hope. May I ask what brand of ambroxol you're using?

[Robb48 in reply to Marie1895]

Sure, bought 1kg from Bionique Pharma in India (via Indiamart, cheapest supplier I could find, US$450 inc postage), putting tablets together on a weekly basis for her.

[rebtar in reply to Robb48]

I'm wondering if you researched the supplier and found them to be reputable and reliable as far as ingredients and contamination in their product?

[Robb48 in reply to rebtar]

I did not, because I am not sure how I would go about doing so. They could provide certificated of purity, lab analysis, which I believe they shipped with the product, but how would I verify? No idea. Just had to go for it. If you can find better, please share!

[LiesBram in reply to Robb48]

Hello Robb, first off all Thanks for your post on Ambroxol, Iam a 57 year old Dutch male, my Parkinson is very progressive and I have been selected for a dbs as the medician i am receiving hardly has any effect in surpressing the symptoms. I have therefore decided to try Ambroxol in accordance your post, I have started using the 75mg Heumann capsules, week 1 3x75mg2 3x150mg

3 3x225mg

4 3x300mg

156 days 3x450mg.

I have als ordered 1kg at you supplier. My question to you is , ,are you making pills or capsules and how do you make them, capsules are i think the best but which capsules size should I use to produce 60mg capsules. Thanks in advance Henk

[Robb48 in reply to LiesBram]

Hi! Good luck, I really hope it helps. I cannot comment on 60mg capsules, since Mum is currently on about 220mg capsules 3x per day, for that I think they are size 1 and not entirely full, size down would be better perhaps but harder to fill. Yes, I fill them by hand using a small tray that I 3d printed, a tiny little funnel I bought on ebay and a 0.01g scale. It's a bit of a pain, a small filling machine would be better, I have meant to look into sourcing a correct size machine but never got around to it.

With ambroxyl, I have meant to edit my post for some time with an update, but not gotten around to it. I will do that now. I am uncertain if ambroxyl affected disease progression, although it certainly improved quality of life, but the effect may have slowly diminished over time. However, we have seen very good results from FMT with the Taymount clinic, I've been meaning to do a post about this but wanted to wait a little while to see how things go. She has had 3 treatments so far, though delayed for various reasons in getting the next treatment (last in October), and it took time to see the benefits - she was not in a good way for some time after the first treatment, there was a definite recovery time after each. I'll try and do a proper post after the next treatment.

[LiesBram in reply to Robb48]

Thanks Robb, maybe a bid off topic but is your Mum only on 3x220mg i.e 660mg a day? and does she uses any other (official) Parkinson medication like Levpdopa/Carbidopa?. and thanks for the tip on FMT I will look at that as well. I am now in my third week with Ambroxol and taking 3x225mg a day, now at day 4 week 3

[Robb48 in reply to LiesBram]

Hey, no problem. Yes she is on levodopa, though I could not tell you the dose, and yes she is only on about 660mg-ish ambroxol per day. My experience when we first started giving it to her was that we saw results relatively quickly, and reducing dose didnt seem to create any problems. However, higher doses can cause issues with dry mouth, something I know from another person mother who has MSA and tried it, and my Mum was having problems with this also. So, 660mg is about where we settled.

[LiesBram in reply to Robb48]

that is about half compared to the clinical trial, I'm now on 675mg a day , unfortunately no results yet apart from nausea and feeling very tired, however not everybody is the same so I'm going to hang in there and build it up to the trial level of 1,26g /day. I heard that for some it gets worse before it gets better.

Thanks for your replies, Henk

[Trudy2020]

Lovely to read your story Robb. I had a break with 600 mg Ambroxol to include magnesium and B12 into my drug regime. Soon as I started back on the Ambroxol two days ago, I’m more able to push myself up and out of bed. So yes positive for result there. Hope your mum will continue to improve. X

[Robb48 in reply to Trudy2020]

Awesome, congrats! And really interesting you are seeing short term relief with ambroxol as well, rather than the months/years of slow burn I had expected.

[Xenos]

Amazing. One of the best posts I ever read on this forum. Thank you so much for sharing this.

[LAJ12345]

That is awesome!

[Missy0202]

Amazing to read and thanks for taking the time to make such a detailed post. I hope this upward swing continues for your mother and the whole family.

[SilentEchoes]

Hi, curious about how you came upon ambroxol as a therapy for MSA. I write often on this forum about symptom overlap in neurodegenerative disorders, which I have concluded are forms of brain injury. I first thought I had MSA because of the early onset of autonomic dysfunction, turns out I have an atypical form of ALS. I'm intrigued about the therapeutic potential of ambroxol for motor neuron disease. Thanks for sharing your testimony.

SE

frontiersin.org/articles/10...

[Robb48 in reply to SilentEchoes]

Sure, I came across it here, remember reading a post from someone saying that it was the only thing that helped their partner (Parkinsons), so I researched more and decided it was worth a shot. The original study indicated that ambroxol may work by clearing out the misfolded alpha-synuclein, which is of course a common factor in different forms of Parkinsonisms, so it was reasonable to consider it might have an effect on MSA also. Even more so given this indicates it may be working on the cause, rather just reducing symptoms. Hugely speculative of course, the original study was more to assess safety, but the fact that they saw a real decrease in Parkinsons related symptoms - not just slowing the rate of decline - is still an excellent result. And, well, the results of inaction are well documented, so what is there to lose except money! I am not sure I agree that these conditions are a form of brain injury though, or at least not exclusively that, given the studies on gut connection, effects on mitochondria, and more recent studies exploring the link to SIRT systems. Too many unknowns though, too many interlocked systems spiralling into complexity. But research seems to be moving forward at a good pace now, and who knows ambroxol and PS128 seems to have incredible effects on some people, if followed up this should expand our understanding.

[JayPwP in reply to Robb48]

DHPSR was our resident Ambroxol expert and promoter, but the account seems to have been closed

[Millbrook in reply to JayPwP]

Sorry to hear that. She was the one I was referring to but I could not remember her name.

[Hidden in reply to SilentEchoes]

Have you heard about the Phenylbutyrate TUDCA study? It is done by two Brown grad students and Dr. Rudolph Tanze of Harvard. In human trial, it slowed motor decline by 25%. Phenylbutyrate was trialed in Colorado in approx 2012 for PD and it looked good. Likely didn’t continue because without it being combined with something it can not have IP rights. TUDCA is currently being trialed for PD. Anyways, you might want to look in to it?

[Robb48 in reply to Hidden]

Thanks, will check it out!

[binnyrox]

Thanks much Robb48 for taking the time out to write in such detail about Amboxol

I’ve been diagnosed with MSA and will definitely check it out.

What dosing frequency do you give your mum for the 180mg - is it split up or a single dose daily?

Please do keep us posted - you’ve been very kind sharing

Very best regards

[JayPwP in reply to binnyrox]

jamanetwork.com/journals/ja...

The 186-day exposure period comprised 28 days of dose escalation, with each dose administered 3 times per day as follows: 60 mg (days 1-7), 120 mg (days 8-14), 180 mg (days 15-21), and 300 mg (days 22-28). This exposure period was followed by 158 days of administration of ambroxol at 1.26 g per day (420 mg 3 times per day). Patients were issued ambroxol therapy in 2 batches, 1 at baseline and 1 at 93 days.

[binnyrox in reply to JayPwP]

Really appreciate the note It’s very helpful and I’ll try it out.

Thanks much

[Robb48 in reply to binnyrox]

Oops sorry, oversight on my part not to be clear on that - I will edit the original post. She is on 180mg three times per day - with breakfast, lunch and dinner. So a total of 540mg. Decided with food was best due to it being easily absorbed, having a short half life and potentially causing stomach upset.

[binnyrox in reply to Robb48]

Thanks much

[binnyrox in reply to Robb48]

Hi again Robb48

Many thanks to you I’ve started on Mucosolvan - brand name for ambroxyl where I live

I happen to belong to the MSA Coalition group as well but find this group has been the most helpful

Just wondering if you would like to post there as well regarding ambroxol

Your sharing has made a world of difference for me - at least something to try when there doesn’t seem to be any thing else

Perhaps it might help someone else similarly over at the MSA group

Just a thought

Again immense thanks Robb48

Very best

BR

[Robb48 in reply to binnyrox]

Hi, I wont share for now, sorry to say but in the last few days she's just crashed down again - but then I ran out of thiamine and some of the other things I was giving her before, and hoped they were unnecessary now, perhaps I was wrong. So we're just trying to get her back on an even keel again. Fingers crossed. Good luck!

[binnyrox in reply to Robb48]

Thanks for the note

[Robb48 in reply to binnyrox]

Hi, just to let you know, I've edited an addendum onto the original post, you may wish to read :). I think I can tentatively say back on track now, hopefully no more issues in the future!!

[binnyrox in reply to Robb48]

Hi Robb48

Thank you so much for taking the time out for the note

I was thinking about your mom and as a fellow MSA patient - you may find some of the following information useful. Pardon the lengthy post but I am writing from personal experience

1. Stressors

With MSA, any stressor brings about a setback. If its small - eg rushing for an appointment, then I may take a few hours / half a day to recover. If its bigger, - eg over exercise at therapy - it may take a day or more. The threshold is rather small so my neurologist recommends doing all activities in what he calls snacks

So there are exercise snacks, speech therapy snacks etc and its done for about 10mins and I rest for an hour till the next session throughout the day. I have been told not to underestimate the value of physical exercise and it has helped very significantly with reducing disease progression

2. Physical Therapy

I am not sure if your mother is mobile. A very important exercise explained to me was a Sit to Stand. It helps keep the lower body strength. Also, having been bedbound due to aspiration pneumonia, I am slowly starting to walk again. I found sitting on a chair with ankle weights and marching on the spot helped with the cadence and the sense of planting weight on my feet. Stretching (including fine motor for the hands) is paramount to prevent irreversible contracture . For cardio, I use a recumbent bike HIIT to get more out of it as I can't exercise for long. If she is mobile then you may be curious about this done at Innsbruck Medical University, a leading centre for MSA research

multiplesystematrophy.org/w...

3. Dysphagia

One of the most problematic area for an MSA patient is swallowing. This can lead to pneumonia. Does she have a speech therapist? If she is still having foods orally, then you might like to view the link below.. From a videoflouroscopy done - I have been prescribed the Masako and Effortful Swallow The best practice for swallowing is simply to swallow the secretions that may collect in the mouth. If I am overwhelmed by it, I rinse and dry it out so that I can restart with less difficulty,

The chest specialist recommends rinsing the mouth many times a day to minimize bacteria pooling and going down the airway accidently. If anytime she sounds gurly, there is probably secretions sitting on the vocal cords that can accidently go down the airway so try clearing it often

southtees.nhs.uk/content/up....

4. Chest Infections

I was recently introduced to 'Cough Assist' and it was a game changer for me. It works much better than a suction machine and less invasive. It also strengthens the lungs in the process.

I use a spirometer and the following exercises have also helped

mskcc.org/cancer-care/patie...

5. Urinary Track Infections

I was having constant UTI until an SPC was done. I have not had any infections after

6. Nutrition

With dyphagia , I was dangerously undernourished and finally had a PEG done. I am now back at a healthy weight and take a combination of home blended food (3x) and nutritional feeds (2x) daily

7. Medications

I am on Madopar and Comtan. The Comtan makes the Madopar work longer and is very effective. For orthostatic hypotention, I take a combination of Midodrine and Florinef/Potassium

A tip you may find helpful - consistently, when my bp is low and its not time for the meds, I take a bolus of very cold water (250ml or more) and it brings my BP up 20 points for about 60-90mins

I am now on the Ambroxyl that your so kindly shared. Its my third week dosage and I feel its been helpful. Easier to do exercises and helps with the walking

Like your mom I'm on many supplements including the Red Helmut and PS128. I believe it's a confluence of many factors that I am seeing a remarkable improvement for a disease that has a very dismal prognosis

Again, many thanks for your posts Robb48, it has been very helpful and please do ping if you have any other queries. I'd be glad to share if I know

PS A patient on the MSA forum mentioned she put her mother on a Gluten free diet and it helped immensely. I have been doing that as well

[Robb48 in reply to binnyrox]

Hi! Sorry for the delay in getting back to you, I appreciate your writing this all out for me though! Extremely kind of you, I'll have to save it for reference. And fantastic that you are seeing such improvements! Re ambroxol, my Mum is back to where she was now before our recent hiccup, which is SUCH a relief. But it is curious talking to her about it, she's not sure if she feels like she has improved, even though it is night and day for myself and my father. I wonder if this is something you have seen? Of course it's hard for her to compare how she feels, to how she felt a couple of months ago, but still. It reminds me of Dr Costantini actually, taking photos of peoples faces before and after thiamine injections to prove how different they looked. Anyway, quickly re the other points you mentioned, yes we have noticed my Mum coughing sometimes while eating, swallowing issues, but it's not so severe yet, thankfully. Still, I had not considered the pneumonia angle, definitely one to bear in mind. She is mobile, my Dad goes out on walks with her typically twice per day. Often short but it's something. With stressors, my Dad had a theory that if she went on walks that were too long, more than she could manage, that it set her back, but I'm not sure. One to consider though!

Another therapeutic angle I've been looking into again in the last few days is telomere based therapies. Listening to interviews with a Dr Michael Fossel, the whole telomere science is fascinating, but not one I've been up to date on for a while. Dr Fossel was the editor of a high ranked anti-aging journal, and the last interviews I can find with him are from a year ago, when he was developing a gene therapy to controllably switch on telomerase and use this (broad range technology) to target Alzheimer's specifically. He was hopeful that they could cure it, but only the data will say for sure. His most optimistic guess then was that they would move into human trials in 2 years, and mentioned that other neurodegenerative conditions would be good initial targets. So I'm hopeful this is something we may see on the horizon soon-ish.... I'd like to get my Mum on a product called TA-65, a telemoerase activator, it's not massively effective but it's all thats commercially available, unfortunately it's also monstrously expensive :). Still, I think I have a bit more kudos with my parents now so maybe I'll cajole them into trying it in a bit! Holding off on PS128 for now, we werent sure if it was making her feel sick and they're off on a cruise in a couple of days (!!!). Have you noticed anything from it? After they get back we'll try it again. I have other angles to consider long term, I think the sertuins approaches are promising, resveratrol perhaps, unfortunately another pricey one. Well, going to take it a bit more gently now! Ambroxol has given us breathing room :). Hope you are well!

[binnyrox in reply to Robb48]

Good to hear from you, apologies for the late reply. Based on what you have mentioned, I am further along the disease than your mum

I thought about it and felt the most useful information I could share with you would be what I would have done differently if I could turn back the clock from when I was first diagnosed

1. Know that MSA can deteriorate very rapidly. For example, there was a period of 2 months when I was being treated with TCM -accupuncture and accupressure. Because of time constraints, I was passive and did not manage to exercise and continue with speech/swallowing practice. When I finally realized it, I had lost my ability to cough, hawk, do strong swallows. Functionally, I went downhill - warp speed - unsteady gait, hand tremors with tasks etc. I know if I had continued being active, the decline would have been very much slower

So practicing doing all important functional activities and exercises daily is very important.

2. You mentioned your mum coughs when eating. That's a first sign of dysphagia. The cough indicates some thing has gone down the wrong way. Her swallowing may have gotten weaker. I didn't realize it and continued eating and have ended up in the hospital for aspiration pneumonia twice. That is not desirable as I became deconditioned (again rapidly) in bed and it takes a long time to try to get back to where I was (and still trying). I would have seen a good speech therapist earlier. A videofloroscopy is usually done to determine the problem and appropriate exercises prescribed. Most MSA patients end up with chest infections so minimizing it is crucial

3. I pushed myself so hard trying to get better. And I'd be so tired out - couldn't do anything for the rest of the day. With MSA, its a little tricky, try doing things up to a level when its just right. My benchmark is that I should be able to rest for an hour and be ready to start another activity. If I can't do that - then I've overworked the system

4. Because MSA is neurodegenerative, , I find the concept of neuroplasticity very helpful and optimistic. I read Norman Doidge's The Brain that Changes Itself and The Brain's Way of Healing. You may be interested. It really keeps me from despair

5. I've also found what really works for me with regards to aspects of MSA medication, managing orthostatic hypotention, nutrition etc. If you do cross that bridge, just ping and I'd be glad to share what has worked for me. I won't bore you with that now

6. The MSA Coalition is peerless with regards to assistance and information. I have written to a few of the professors and doctors associated with the organization with regards to issues and they have reverted promptly and have been incredibly helpful multiplesystematrophy.org/

The world forefront chap would be Professor Gregor Wenning. There are experts in various areas,- check them out in the about us

Well that is all I can think of. You have been so kind with the Ambroxyl lead, I am now on 300mg thrice daily. Your mother is very lucky with you helping her out

Take care and best wishes for your mum

BR

[Robb48 in reply to binnyrox]

Hi, apologies again for the late reply! And again, thanks for the info. Yes, we have seen periods where my Mums condition has rapidly deteriorated, which confused us, so it is useful to know this can happen. And also thanks for the other details, I wont reply in detail now but it is useful! Another one you, if you are interesting in cutting edge research. I was unsure for a long time what the bodies normal mechanism is for clearing the misfolded synculein, discovered the other day that there are two pathways for this, and one is autophagy. Autophagy appears to be a somewhat broad heading, but is useful, because it is recognised to be impaired in all neurological conditions, and can be targeted. I went looking for trials on spermidine, a compound found in many foods but sold in the form of wheatgerm concentrate, it boosts autophagy, although unfortunately it is another extremely expensive supplement and quite new to the market. However, I found one trial for dementia in which it actually improved the condition of test subjects - didnt just slow their rate of decline, it actually improved their dementia score. Which is highly interesting, although they "administered" it in the study by feeding the individuals bread rolls! Also trials on older adults at risk of Alzheimers, with subjective cognitive decline, etc, which all came up positive, and used actual extract pills I think. There are other trials with animal models on synuclein that look good, but very basic animal model (fruit flies and flat worms if I remember right). So this looks hopeful to me, as it is addressing what may be a key pathway in the disease condition. One to consider perhaps.

[binnyrox in reply to Robb48]

Really , appreciate the leads - will definitely check them out including telomere from your earlier postTake good care of yourself too. Must not be easy with the juggle

Keep in touch, was very good chatting with you

My best

BR

[Robb48 in reply to binnyrox]

Thanks, you too!

[binnyrox in reply to Robb48]

Hi Robb

Trust this note finds you well.

I have just been prescribed 2 medications that really was life changing and thought you may be curious

1. Opicapone brand name Ongentys. This is a new generation drug that made my Madopar "on' periods last longer. I take it at night on empty stomach and 1 hour after my last Madopar

2. Amantadine brand name Symmetrel. This made a huge difference to my movement and speech. My speech therapist uses the IOPI machine and it registered a 50% improvement after 2 weeks of using the above drug protocol. My chest physio measured my inspiratory and expiratory volumes and it has also increased about 40%

I recently changed neurologists- he came highly recommended by a board member of the MSA Coalition. I had been very conservative with my Madopar for fear of dyskinesia. However, this professor mentioned in the case of MSA, Madopar (levodopa) very rarely causes dyskinesia as a side effect. In his years of practice - he has only come across 1 MSA patient with dyskinesia from Levodopa

With Parkinson's patients - dyskinesia is common with Levodopa

With this knowledge, I am now taking good therapeutic Madopar doses at helpful intervals and finally achieving good progress with my therapists

Just FYI and my best to both you and your mother

Kindest regards

BR

[Robb48 in reply to binnyrox]

Hi! Sorry for the late reply, saw this come in when I was bleary eyed one morning and then just straight forgot to check up. Thanks for letting me know though, these sounds really promising! And Amantadine seems to be available to buy online (in UK) without a prescription, brilliant, I'll definitely look into. Fatigue is a massive problem for my Mum. For extending useful time with levadopa, we use it mostly to control her twitching now, but anything that keeps the pills going longer and smooths the effect would be great. It's really excellent to hear you've found something that works for you. Ambroxol effects basically stopped at what I mentioned in first post, good to keep her interacting with us, but didnt effect her physical condition, which has continued to deteriorate.

Thanks again!

Rob

[LeharLover62 in reply to Robb48]

If you’re interested in telomere length research and treatment, check out this Israeli company who are using hyperbaric oxygen therapy combined with cognitive therapy to treat neuro degeneration. They have a facility in Florida also:

shamir.org/en/unique-pages-...

[Robb48 in reply to LeharLover62]

Nice, I wasnt aware of an HBOT - telomere connection, will have to look into, thanks. I've seen research that suggests HBOT increases circulating stem cells, looks like a really fascinating approach. I actually got in contact with a local-ish HBOT treatment centre in the UK, they werent familiar with treating MSA, not surprising, so asked their own experts, who basically said yes it can be effective (as some have claimed for MSA) but that you need something like 2 sessions a day for a couple of weeks!! Not a once a week cumulative thing. And the local centre were unable to give us that much time, unfortunately, so, a tricky one to follow though. I did find a company (in Austria? I think?) who were able to sell soft shell units that can reach 2+ bar that you can use at home, but no doubt at a serious price, and then you need to figure the oxygen connection, which also has its own safety concerns so... quite a hard sell :).

[faridaro in reply to LeharLover62]

I checked out the affiliated HBOT center at the Villages in Florida and found out that treatment involves 60 consecutive sessions during 12 weeks at the price tag of $60,000 ... 😲

[LeharLover62 in reply to faridaro]

Yikes! They’d have to be getting amazing results for that to be worth it! I think you can find the HBOT treatments for less in lots of cities in the US but maybe without their specific cognitive program.

[Robb48 in reply to faridaro]

Eeeek! $1000 per session, wow. Yeah, at that point I'd be thinking of buying my own unit, or finding a clinic somewhere exotic like Thailand and going on holiday for a couple of months :). Crazy price though, there is a clinic in London (UK...) where you can buy packages with a cost per session down to £131. The charity centres in the UK are much less, but are very busy.

Hah, I've seen some interesting home builds online too - from the really well done profession types, to the Russian guy with a bunch of sheet steel and a welding torch :). Whatever works I guess!

[Fighttolive]

Hey Robb, glad that your mom is seeing improvements. I have ambroxol in the closet still waiting to try. I've been on ps128 for about 3months and at first the improvement did not show, however the last month , my symptoms (tremors, fatigue, anxiety, insomnia) have diminished significantly. I've also cut sugar and carbs off, I truly believe the combination is the cause of the improvements. I was reluctant at first to attribute ps128, it may be the mind or body adjusting to the PD , meds after experimenting for 3 yrs, but after 2 months of steady improvements I'm beginning to have hope that I can survive long enough to see my 3 and 8yo grow up. Keep fighting for your mom and good luck.

[Robb48 in reply to Fighttolive]

Interesting! Most the other reports were from people seeing results for PS128 in hours to days, good to know benefits can still happen on a longer timescale. Good luck to you too! Keep fighting :).

[Hidden]

"I'm a little hesitant to post this, as it is still VERY early days, but if there is any chance that what I am seeing is caused by ambroxol, and if it might be replicated by other people, then I think I have a moral duty to put it out and give people the option to test for themselves, or their loved ones."

I think you have no proof that ambroxol does anything positive, and no "moral duty" to suggest to people that it might (nor can you say it has no negative effects).

"However, the improvements have been (mostly) steady and consistent, and I'm struggling to think of anything else that could cause it."

No need to struggle any longer, it is most likely a placebo effect, which is strong in people with Parkinson's, and can actually work quite well, until it doesn't

But don't feel bad, this is what this site is mostly all about - people suggesting that they have seen an improvement, and attribute it to some supplement, or some apparatus, and the rest of the folks going and buying it, and then trying it on themselves...

[Robb48 in reply to Hidden]

Nope, not placebo. I'm not the one taking it, and I didnt expect these improvements. They are, as I said, quite striking and obvious. That said, I was quite explicit in saying multiple times that I had no "proof", just putting it out as it is. People can make up their own minds.

[Hidden in reply to Robb48]

I think you don't understand the placebo effect, for if you did you wouldn't insist there is no placebo effect in you grandmother's case...

[Robb48 in reply to Hidden]

I think you have not read my post, because the person in question in my mother. And again you make presumptions about me and my situation. I understand placebo very well, and recognise the scale of effect it can have, but in this case nobody expected effects, yet they have been strong and sustained. Make up your own mind, decide I am an n=1 case you cannot verify, fine, I have no problem with that, in fact I would encourage it, but to TELL me it is probably just placebo, and that I shouldnt feel bad - oh thank you, how magnanimous of you! - when you know next to nothing about the situation? You think I have not considered that, with something so serious? Please. I could go on, with specific metrics and behaviours, but I think there is no point. I will not continue this conversation.

[Hidden in reply to Robb48]

I did read your post and understood that the patient was your mother.

"in this case nobody expected effects"

So she took some medicine with no expectations or hope whatsoever of a positive effect? I am not sure how you could say this.

"I will not continue this conversation."

OK. Good luck and peace.

[Robb48 in reply to Hidden]

OK, I will answer the question. No, none of us expected any results - in the short term. I have thrown a LOT of stuff at her to try, beyond the things discussed on this board, and hoped and expected some of them to have results, such as HDT. None of them did, at least nothing significant, and yes I was looking and hoping constantly to see improvements in her. And telling her what I hoped to see. If placebo was active, it would have been much more active with previous supplements etc I tried her on. Conversely here, I considered it enormously speculative, and told both my parents that if there were going to be effects, we would probably see them 3-6 months in, perhaps longer. So when we saw improvements in the first week, and my Dad asked me if I thought it could be the new supplement, I said no, that it was very unlikely. Even when it looked more probable, I was constantly cautioning myself against misplaced hope. I'm beyond that now. She is, without a doubt, improving, and I cannot see any other explanation. So, yes, I can reasonably rule out placebo as a cause.

.....and you said grandmother.

[Hidden in reply to Robb48]

"and you said grandmother."

You're correct. I mispoke. But it is a "red herring", for nothing I have asserted in my original response, has anything to do with the identity of the patient.

Now I am done...

[SilentEchoes in reply to Hidden]

The placebo effect doesn't apply here, the mother doesn't appear to have the capacity to know or decide what meds she's given and is unbiased. Robb48 is the observer in this case and it is a legitimate report. Levod, no one is twisting your arm to take/try ambroxol. I am going to give it a go based upon my own research and combine it with NAC and appreciate that Robb48 wrote the post.

SE

[Despe in reply to SilentEchoes]

NAC can be used in a nebulizer.

[Godiv]

That’s wonderful Robb 48!!! I’m so happy for you and your mom. Definitely keep us posted but it sounds great. She is indeed very lucky to have you. A difficult part of these kinds of illnesses is doing everything on your own. I realize your mom wouldn’t be up for that anyway. But sometimes I wish I had someone who was frantically researching things for me and with me. The burden often falls on the patient. But of course this forum helps so much and everybody is so knowledgeable and nice about things. Anyway, thank you for the good news!

[Robb48 in reply to Godiv]

Thanks, I am sure trying to do everything on your own must be incredibly difficult, well done for pushing forward anyway! So many other people here looking for solutions, it's really fantastic.

[Godiv in reply to Robb48]

Thank you! It gets a little difficult sometimes LOL. But yes the forum is great. It empowers all of us to search for solutions or some thing that will at least help.

[SilentEchoes]

Robb48, what are your mother's atypical symptoms?

SE

[Robb48 in reply to SilentEchoes]

Sure. So first the persistent feeling of indescribable sickness or unwellness, generalised but also related to the gut, none of the specialists really know what that is about. Also orthopaedic hypotension is classic in MSA, which she seemingly didnt display at first, even when other symptoms were presenting fairly severely. With the first specialists she saw, he tested her exhaustively but it wasnt present, he gave a very tentative diagnosis of MSA at the time but was quite unsure. Later tests have shown a mild form of orthopaedic hypotension. Sleep, insomnia is less common I *think*, though it can be present, more regular is excessive sleep or sleepiness. But MSA presents as a spectrum, I emphasised atypical because I dont want to imply any certainties with regard to reproducibility.

[Despe in reply to Robb48]

Our Vanderbilt MDS had explained to us the different symptoms for different neurodegenerative conditions. He told us that MSA never or very seldom presents itself with resting tremors, but patients experience muscles twitching.

[SilentEchoes in reply to Despe]

For Robb48 too: the muscle twitching is called fasciculations. They are found in parkinsonisms (MSA and atypical ALS (see Table 1)). ncbi.nlm.nih.gov/pmc/articl...

So how do you tell them apart? Reflexes. They are normal in MSA and hyper in ALS and in MS. Fasciculations occur in MS too, which along with ALS, is a neuromuscular disorder (so is muscular dystrophy).

Dementia co-occurs in ALS about 50% of the time, FTD or frontotemporal dementia is part of the ALS spectrum. If dementia is present it is something other than MSA, such as PSP.

neurologyadvisor.com/topics...

The line is blurred between the neurodegenerative disorders.

SE

[Robb48 in reply to SilentEchoes]

Thanks, yes with my Mum she gets leg twitches at night, but no tremors, and definitely no dementia thankfully. Understood about blurred lines, hard to say for sure sometimes.

[pmmargo]

This recent paper mentions ambroxyl and the associations between GBA mutations and MSA peripherally. Have you had your mom tested for other mutations? (There are over 300 of them). I hope she doesn't have it..it is supposed to be super rare. Since ambroxyl is working I wonder if she has N370S.

[Robb48 in reply to pmmargo]

Hi, no I have not - genetics is not an area I've looked into in depth, only peripherally aware that genetic components are a bit controversial. 300 mutations seems to be a wide range of possible associated genes, rather than a direct genetic cause! I'll check out N370S though thanks.

[SilentEchoes]

Here's a source for ambroxol.

Retail box of Ambroxol 30mg tablet

[LeharLover62]

I agree with the theory that the thiamine may have caused insomnia. For hubby, too much thiamine or too much dopamine will lead to anxiety and sleep issues. This resolves when the dosage is right and he is “in the zone.” Gonna look more into ambroxol though, sounds promising! He has the speech issues also.

[Robb48 in reply to LeharLover62]

Interesting - I was wonder about the right dose range re thiamine and sleep, if there was a sweet spot that helped, as you say. Good to know you've seen a similar thing!

[Router_]

Hey Robb, is there any update on how the condition changed over time ? Did she sign up for the exenatide trial ?

[Robb48 in reply to Router_]

Hi! Her condition continued to deteriorate unfortunately, though more recently she has been having FMT treatments with the Taymount clinic, and seeing very positive results. She did get on the exadatide trial, but only as a control - although that itself turned out to be useful, as we were able to see that her MSA score went from 19 down to 14 after the FMT treatments. Though it is a bit more complicated, I will do a full post about this at some point, probably after her next treatment.

I'll update my original post with an update.

[Router_ in reply to Robb48]

Thank you - that would be very helpful indeed as I am also looking into FMT for early stage MSA. Would be great to understand your observations - immediate reaction vs. how long until you saw any type of reaction to it. Also, motor symtpoms vs. autonomic symptoms. Given that you go for recurring treatments, is your working assumption that the gut requires recurrent treatments ? Did you have a stool analysis prior & post ?

[Robb48 in reply to Router_]

Very sorry to hear about your diagnosis. Sure, I can give more details now. So she has had 3 treatments, which were a month apart, and the last one at the start of October, but we have been delayed in getting the next one for various reasons. After the first treatments, she was suffering for some time, with a general worsening of symptoms, although there are other factors that may have affected this. I would say that we started to see improvements perhaps a few weeks after second treatment. After the third treatment, a week or two of difficulties. My pet theory on MSA and Parkinsonisms in general is that there are bacteria or some other flora in the gut which attempt to alter the local environment in a way that is beneficial for themselves, perhaps slowing gut motility or attacking the bodies gut homeostasis mechanisms, and the disease conditions we see are unintended side effects, specifically impacting mitochondrial health, and creating all the other conditions such as synuclein accumulation as downstream consequences. Parkinsonisms can then be seen as the body losing a battle to control gut flora, and according to this theory then it could take multiple FMT treatments to allow the body to heal or regain balance. But, this is just my pet theory :). From discussions my parents had with the founder of Taymount, who we were very privileged in that he took my Mum on effectively as a private patient, there are auto-immune conditions that can take multiple treatments before the body is kicked back into a healthy balance. However, it could be that if she had only had one treatment, and we had waited long enough, we might have seen positive effects. Anyway, she had a stool analysis perhaps a year or two ago, and tailored pre and probiotics, but nothing much to report, similarly with PS128 which I tried her on. No gut tests since treatment. Improvement in symptoms, I cannot comment too much on autonomic issues, she has seen orthostatic hypertension in the doctors office, but she does not tend to get dizzy when standing (apart from perhaps at night), and this is not something I have been personally paying attention to. And I do not discuss her bathroom habits with her in great detail! But her exercise capacity has definitely increased, and though her balance was negatively affected after earlier treatments we did actually see significant recovery of this before Christmas. The last 6 weeks or so have been more complicated, as she had a fall before Christmas (tends to get overconfident when she is feeling good), and broke her collarbone, then we switched to another packet of thiamine (she has been taking powder for some time, redwells brand), but the new packet around Christmas must have been bad, because her condition cratered literally overnight as soon as we switched and she took a long time to recover from that (changed to Solgar 500mg tablets). Otherwise I would say general normalisation of communication and facial expressions, improvements in her sleep (before Christmas her sleep was basically normal and good, sporadic problems again now). And most of all for her, the feeling of sickness that was probably her first symptom, completely disappeared for a long time, until coming back with more recent problems, but even now she feels relatively fine many days. So that is a huge improvement in her quality of life. And like I said, the improvement in MSA score, which "puzzled" the specialists who were testing her to the point that they quizzed her about it and said they may have to exclude her results from the trial when they discovered she was having FMT treatments! The sort of tests she was given are not exact of course, and do have fairly wide error margins, but still, the doctors did seem to consider her result anomalous.

Anyway, long reply, since you have MSA I thought I should fill in a bit more! Caveats though, I know of other people with MSA who dont seem to benefit from ambroxol or thiamine, and these have had strong effects on my Mum, so who knows whether FMT will help you. Another caveat, you may have seen research coming out of China on FMT, I now know something of an inside line on the team that did that - they basically picked the brains of a Western expert, and made it seem like it would be a joint venture. They then went back to China, cut off all communication, apparently carried out the research that had been suggested to them and published it entirely as their own. So, a certain question mark regarding their ethics. However, assuming they actually did the research and got the results they claimed, you can also see that there was a range of results from the PWP they treated. All that said, in your shoes, I have to say that I would not wait. Once neurons are gone, it is hard to bring them back..

I hope this is helpful, good luck!