This post is technical in nature so I hope the non-technical folk will forgive me.
If you are new to this site or to my posts, let me start by saying that I have SCA1 but have managed to keep my symptoms at bay. I believe I am doing so with a simple combination of diet, exercise, and carefully chosen supplements. For more information about what I am doing look here: healthunlocked.com/ataxia-u...
Now today's post is a discussion about a scientific aspect of the research surrounding ways to treat polyQ disorders as well as other neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's.
For several years now, I have come to the conclusion that what all these diseases share in common is the presence of proteins in the brain that somehow become toxic. In scienctific terms, all the proteins in question are able to form oligomers. What that means is that for different molecular reasons these proteins all fail to attach to other molecules in the brain in a proper fashion and end up not getting removed from the brain at the proper time, a process called autophagy. It is the combination of these two scientific processes that underly my theory on the supplements I chose. It turns out there are molecules in nature that have a natural affinity to both stop toxic proteins from forming oligomers and help the body perform autophagy or in other words the natural molecules stop the toxic proteins from clumping and sticking around longer than needed.
What is critical to understand in this discussion is that delivering small molecule proteins to the brain capable of preventing oligomerization and enhancing autophagy is WAY WAY WAY simpler than trying to repair DNA, and until recently researchers have all been focused on repairing DNA rather than simple protein clearing, BUT it looks like top researchers are starting to pay attention. Here are 3 quotes from recent papers:
"These conclusions highlight the importance of studying both the loss and the gain of function of aggregation-prone disease-driving genes, particularly in the context of their native complexes. Our studies suggest that disrupting the ATXN1-CIC interaction, either pharmacologically or with a small peptide, will bear fruit for the ataxia in SCA1."
"Our findings for SCA1 are likely to be applicable to other members of the larger family of neurodegenerative proteinopathies. It should be worthwhile, for example, to explore whether native interactors of tau and α-synuclein might promote or hinder their formation of toxic oligomers. Without ruling out the role of non-native interactors in protein aggregation, we propose that neuropathological features of a specific disease are determined by both transient and stable native protein interactions and that these interactions in turn affect the amyloidogenic properties of the disease-associated protein. Thus, blocking certain interactions that mediate the formation or stabilization of oligomeric toxic entities, or modulating the downstream effects of such interactions, could be an attractive treatment option for this class of diseases."
"Future efforts are required to understand which structures within the A11 epitope facilitate 20S proteasome binding and impairment and if this phenomenon occurs in human disease conditions. Elucidation of this mechanism provides a compelling model to explain why proteasome function has been found to be impaired in virtually all neurodegenerative diseases. Interestingly, Choi et al.77 showed that opening of the 20S proteasome gate in cells leads to enhanced cellular proteasome function, including ubiquitin-dependent protein degradation, decreased protein aggregates, and protection from oxidative stress. Our model provides a mechanistic framework to develop small molecules to counteract proteasome impairment via A11+ oligomers. Illustrating this potential mechanism of proteasome impairment identifies novel drug targets for developing small molecule activators of the proteasome gate. Such therapeutic interventions have the potential to restore proteostasis in patients suffering from neurodegenerative diseases."
Alright Joe that's all well and good, but what does this MEAN?
It means scientists are coming to the conclusion that the best way to treat SCA may be with small molecules and that is exactly what the supplements in my regimen have evidence they MAY be helpful in doing. So . . . we all need to drink more Green Tea with trehalose
Joe in NY
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Thank you Joe! I've said it before.....but what the heck i'll say it again.....your positive, hope-filled posts keep my spirits up! No pressure.....but keep 'em coming 😉😁 My husband has long dis-engaged with the health professionals as there was nothing but doom coming from them.....but he takes his suppliments and is (trying to stick to) doing his running because of the research you share.
Thanks! It means the world to me that some of my posts give folks hope at least.
As to exercise, it was my personal experience that too much of a good thing wasn't actually helpful. 30 minutes 3 times a week at 80% max heart rate really worked for me AND is very doable in terms of discipline. Don't know if your husband is still doing higher mileage or not, but perhaps he could try 30 mins 3x at 80% along with weight training for his quads and hamstrings for a month or two and see if he noticed any difference.
Anyways, cheers everyone! Let's all keep our fingers crossed some pharmaceutical company decides to study one of the myriad molecules that show promise at stablizing oligomers
I've been meaning to write you for sometime but had never gotten around to it. I see that many people, including myself, follow your posts and are greatly inspired by you. You certainly are a hero to me, and I'm sure to a lot of other people as well. I feel a connection to you because I also have sca1, am about the same age, was diagnosed in 2016, live only about 80 miles from you in Northern New Jersey, and fly United back and forth from Newark to Jamaica all the time. Also, I've done tons of research on this disease and believe in a natural approach to it.
As I said, I was diagnosed with sca1 in 2016, with 41 and 33 repeats (whatever that means). I got it from my father who had it, along with all 6 of his brothers and sisters. I have most of the same symptoms that you had, except for he fatigue; but my main complaint and problem is my difficulty in just plain walking, which you don't mention having. But I'm not nearly as bad as some people and I can walk laps unassisted around a grassy field, or a mile or so on a flat beach. But everywhere else I need something to hold onto. I use my husband as a crutch, and rolling suitcases work well for me.
I bought all of the supplements you take and follow your regimen, except for the diet part. I'm able to work out pretty normally and do my cardio on an elliptical, because that's what I have and I could never run on a treadmill. I could barely even walk on one and never without holding onto both sides (I read your article about using a bike). But I work out pretty intensely at least 4 days a week, and I try to keep my heart rate up to 80% for 30 minutes on the elliptical. I also do a lot of stretching, balance exercises and leg work with weights, because my legs are so weak.
But, unfortunately, nothing is working to help me with my walking. The only thing that ever helped me somewhat was taking 4 Aleves, but they usually don't work. I'm seriously considering trying exosomes (a form of stem cells?), and scalp acupuncture. (Have you done any research on either of these?) Obviously, I'm pretty desperate to get at least a portion of my life back. The disease has devastated me and taken much of my quality of life.
Well, I just wanted to introduce myself and thank you for all of the research you do and giving us your regimen. Of course, I'm going to keep at it since it can't hurt, and it could help in time. God bless you!
Thank you so much for sharing your experiences. I'm sure it means as much to everyone else as it does to me just to know others are listening and sharing.
Unfortunately, I have to share an opinion that is not of a positive nature. The fact of our situation and my regimen is that there is no reason to expect that it can reverse damage already done. The best we can hope for is to keep the status quo or slow progression when using an alternative therapy of diet, exercise, and supplements. My symptoms were very, very early with minor balance issues, speech, and writing., but importantly I could still run.
I am not a doctor, and don't want to come across as if I am prescribing anything to anyone, but I will say I believe in my heart of hearts that what you are doing will stop your body from getting appreciably worse so I hope the fact that regaining "normalcy" is unlikely won't discourage you from continuing to fight the fight. SCA1 is normally quite intractable so if you feel no change after 6 months or better yet 1 year then I would consider that an enormous win.
I will add 2 positive thoughts though:
1) Previously I have linked to a study that showed treadmill exercise while supported was helpful in improving gait, and that study and my own experience makes me believe that walking fast helps retrain the brain in a way that one can actually feel so perhaps you could try fast treadmill walking while holding the rails and see if you notice any change afterwards.
2) I don't know if your doctor has already prescribed therapy, but the study linked below showed that "improvements are equal to regaining 1 or more years of natural disease progression" so perhaps that type of therapy could work for you in reversing symptoms slightly:
Thanks so much for taking the time to reply. I guess I misunderstood you when I read that you had symptoms and now no longer do. That gave me hope that you had figured out a way to reverse the damage done, although it was minor in your case. I feel like my case is also still minor compared to a lot of the people, so I still have hope that it can work for me. Like I said, I haven't even added the diet part yet and could be more consistant with taking the supplements.
But, like you, I feel that excerise is one of the most important things and know that it's helping a lot. That's interesting what you said about the speed. I will now try to do that more on the elliptical. Before, I was adding the most tension to train to regain strength, but that made me go slower.
As far as PT goes, in my experience, it's just been an excersize routine that I can do at home, and be more efficient at it.
I will continue to try everything I can, and I thank God for people like you who really dig deep into technical studies and bring us the info you find.
Thanks again for all your posts, and for giving me direct access to you with your email address.
I totally agree with you about most PT being able to be done at home, but I just want to emphasize that the first study I linked deals with very specific training involving using a blind fold and computer games to retrain the brain. That is the study that showed a reversal of symptoms for some patients. My sister is a licensed physical therapist in CT. She read the study and came up with a home therapy. I stand on a couch cushion and close my eyes and try to stand on one foot. At first I couldn’t even close my eyes and have both feet down. Now I can stand for short periods on one foot with my eyes closed while standing on the cushion.
Just wanted to tell you a few things about me, and give you fair warning about my experience with stem cells. I am a 67 year old (!) woman with SCA 6. AT about age 50, I started to show symptoms so others would notice (esp. gait, coordination, etc.) Now I have been in a wheelchair for nearly four years as I progressed from not being able to walk on some surfaces, to not being able to walk at all without support of another, to a walker, to a wheelchair. So. of course I am more dependent on my husband (who is 70) and by last Sept. was very (and still am) desperate. I responded to an ad regarding stem cell infusion, went to a seminar where it was touted, and ultimately my husband and I both had infusions (a single one each) on Sept. 27, 2018. I left hoping for something to happen.
Nothing was promised, though I think it was over-hyped for the stage it is in (just the beginning to middle stages of what is possible). I'm convinced that stem-cells or gene-splicing will be future treatments for those who survive 10-15 years for them to develop it. To make a long story short, neither one of us has noticed ANYTHING! I was hoping at the very least some improvement SOMEWHERE , but nothing! My husband has also had no improvement (he had some joint issues which he was hoping to improve). Just thought I'd let people know. Regards, Daisyone
Wow, thank you so much for sharing your stem cell experience with me. I'm sure that you lost even more than your hope in it; I'll bet they charged you a fortune for it too! What kind of stem cells were they and where did they come from? Where did they inject you? Where did you have it done? Do they have a website? (You can message me if you prefer to keep this private.) I'm so sorry that it didn't work AT ALL for you!
My apologies for not getting back to you-I in fact just learned how to check to see if anyone had responded to my posts this morning! You are so right about it being expensive--it would have been $15000.00 just for me, but we got a " bargain" of "just" $20,000 for husband & wife to get one infusion each!! it was done in their facility by a licensed doctor and he infused us in the usual iv spots--the arms--the ONLY reaction I had was I felt excessively hot, like a fever, for at least 3 days afterward! I have been trying mightily to recall the name of their website, but can't recall it. I probably will in a day or two and if I do I will let you know. If you google stem cell therapy you will get lots of websites. The stem cells were not harvested from us, but independently harvested. I would warn you off of the website (if I could remember it) because I feel now that they prey on desperate people.
Carol, I registered on Joe's website, ONLY to forget about it completely...no idea what's the difference between sca1 and 2, I have the type 2...cannot do the treadmill, even when still ok in the gym, felt weird, maybe pre-ataxia sensation...this was times when I wasn't diagnosed...always had a skin problem, masking ataxia, as all my other friends had eczema (in joints), I had it all over my body, susceptible to fatigue, malaise...but nothing like ataxia...when I think had an occasional drill in my tongue (prior to ataxia), so it must have been there sleeping...always had coordination problem, can't drive...(just as well, cannot judge distances well, slower reflex...shortisisghted heavily...Went on the Keto diet, easier for me to prepare the meals for my husband (he takes it more strictly than I).
As I am in England, only half British, I struggle with some American terms. I can still walk, but aided with a rollator (4wheels, walker), have adaptations made in the house (bathroom...). Cannot walk on the grass, our lawn uneven anyway...and feel safer when holding onto railing, in shops leaning on trolley.
Experiencing fatique, rest at lunch time....Life is not what it used to be, but not complaining...not a sporty child/adult...hate bicycling outside, NOT STATIONARY, my gait widened, exper. some swallowing difficulty, occasional choking...seeking speech therapy...to point me into the right direction...
Always interested to read your posts. They continue to give me hope that if not for me then surely for my children and grandchildren there will be some breakthrough to cure or treat this disabling disease. I am fortunate that I was 71 before I had the first symptom (I am now 78). I am now very wobbly and walk with a frame when outdoors but I try to exercise each day and have a recliner static bike at home and go to a personal trainer in the gym once a week who helps me to get on the treadmill (about 15mins walking) and then weighted arm and leg strengthening excersises. My aim is to slow down the progression. Following your posts I have now started drinking green tea and since January have added trehalose on cereals and soft fruits. I have read today that trehalose is not easily digested through the intestines and to get any benefit it would have to be injected or applied topically. It is pleasant to take so I will continue to take it but would be interested to know your thoughts on this.
Thanks for the kind words. Quick note on trehalose. Yes, 98% passes thru most folks undigested and a tiny bit more gets digested in the lower intestine depending on how much of an enzyme called trehalase one has in their lower intestine. That is why this study had people taking 100g daily to show benefit:
and the hope is that the tiny amount getting into your blood stream everyday ends up getting a teeny-tiny amount into your brain. To me the key factor is that SCA takes decades and decades to begin to show damage. I like to hope that a teeny-tiny amount of clearance might be enough to slow down a process that is already pretty slow in terms of human lifespan.
Anyways, thats probably a longer explanation than you were looking for, but there it is. Yes, most of the trehalose passes right thru you, but 1% of 25 g a day is .25g theoretically making into your blood stream, and like I said the amount of toxic protein is incredibly tiny in amount so MAYBE just MAYBE .25g a day is enough to have an effect.
Thank-you for the research insight Joe! So appreciated as always.
I'm intrigued what your insight on the cerebellar Purkinje cells?
I've read this cell loss is greatest in sca 2's, interestingly these cells produce the neurotransmitter GABA, leading me to think there may be a GABA/Glutamate imbalance which can cause cell death. I know taurine is on your list which does help this imbalance, which is great!
Secondly, with your regimen do you tend to try take the pills with food, or on a empty stomach in the am due to fasting?
One more, sorry! Do you mind me asking how long it took till you found improvements in your symptoms?
Sorry for the slow response, work, life, family you know
Anyways, regarding Purkinje cells and glutamate, I’m at a bar and using an iPad at the moment so it’s tough for me to get the link and post it but one of the first links in my main regimen posts is a link to Dr. Bredesen’s YouTube video about his therapy. The point I want to make is that he talks about how fixing neurodegenerative diseases is like fixing a roof with many holes. A pill that fixes one hole won’t fix the problem. Purkinje cell death and glutamate blocking are both “holes” in the ataxic brain but there are many others. Each supplement I take has a theoretical role in fixing the proverbial holes in my brain. Sadly there is scant human scientific evidence to support my hypothesis, but my contention is that they are all proven harmless at worst so why not give it a go since the supplements all worked on mice 😀
Next, I take the supplements first thing in the AM when I wake up and then again just before bed.
Lastly it was a month before I felt my first improvement.
Thanks Joe, yes I watched that video thank-you, indeed many holes! But so motivating that the supplements aren't scary and positive research associated with them.
What is your take on mushrooms as a therapy? There is a study on Cordyceps as a treatment for SCA (University of Algarve, Portugal DR. Clevio Nobrega) autophagy & to reduce the production of the mutant proteins. Interested to know your take, the mushroom brain list seems to extend to Chaga, Lions Mane, Reishi!
Nilotinib and related tyrosine kinase inhibitors seem really (okay, I understand why people hate this word, but no other fits) promising.
You may be interested in this approach to tau clearance in AD (though it sort of flies in the face of the whole 'the root of all chronic disease is excess O-GlycNAcylation' thing* so I am interested to see where this goes):
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