I’m 45 with PD. I can not conceive of anything I will not do if it will slow this train down.
I’m already doing all the standard recommendations; strenuous exercise, non-dairy keto, the supplements, the red lights, etc. I’m hoping to please not delve in to those options.
I am hoping for help in deciding if I should continue to pursue the Neuraly trial which is Pegylated Exenatide, or if I should look for a doctor who will prescribe Exenatide off label (I may have found a doctor who will) or if I should take Ambroxyl which I already have in my possession (from a French company.).
Please, if you are knowledgable on the science and trials of these drugs, can you help me evaluate these options?
First thing that occurs to me as that with the trial, there's a risk you get the placebo, and you probably won't know that you did for quite a while.
I would say that, at this point, there is more compelling evidence for the efficacy of exanatide than ambroxol, on the basis that there has been no blinded placebo trial for ambroxol for PD.
Either way, you need to get comfortable with the odds of an adverse event from the dose you are taking (note that this may differ considerably from the standard dose suggested for the condition for which the drug was originally created) and for the length of time you plan on taking it.
One thing to remember is that, whilst YOPD sucks, it is better than YOPD plus a damaged heart, liver, kidney or some other reasonably significant organ that may be damaged by off-label prescription drug use. Having PD doesnt mean other stuff cant go seriously wrong. Now, i agree that this risk will be worth it once efficacy is well established (by a ph3 trial, i guess). Before that? I am not so sure.
There's a poster on here that is taking a fair bit of ambroxol and i think he/she has links to studies that discuss long term use? I dobt remember the details (sorry) but it will be in the ambroxol threads.
There's some others that have used Exenatide before like pdpatient and he/she may have some good info about long term use at the doses suggested in the trial.
" Between June 18, 2014, and March 13, 2015, 62 patients were enrolled and randomly assigned, 32 to exenatide and 30 to placebo. Our primary analysis included 31 patients in the exenatide group and 29 patients in the placebo group. At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1•0 points (95% CI −2•6 to 0•7) in the exenatide group and worsened by 2•1 points (−0•6 to 4•8) in the placebo group, an adjusted mean difference of −3•5 points (−6•7 to −0•3; p=0•0318). Injection site reactions and gastrointestinal symptoms were common adverse events in both groups. Six serious adverse events occurred in the exenatide group and two in the placebo group, although none in either group were judged to be related to the study interventions."
"Results Of the 18 participants (15 men [83.3%]; mean [SD] age, 60.2 [9.7] years) who completed the study, 17 (8 with GBA1 mutations and 9 without GBA1 mutations) were included in the primary analysis. Between days 0 and 186, a 156-ng/mL increase in the level of ambroxol in CSF (lower 95% confidence limit, 129 ng/mL; P < .001) was observed. The CSF GCase activity decreased by 19% (0.059 nmol/mL per hour; 95% CI, –0.115 to –0.002; P = .04). The ambroxol therapy was well tolerated, with no serious adverse events. An increase of 50 pg/mL (13%) in the CSF α-synuclein concentration (95% CI, 14-87; P = .01) and an increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% CI, 40-137; P = .002) were observed. Mean (SD) scores on part 3 of the Movement Disorders Society Unified Parkinson Disease Rating Scale decreased (ie, improved) by 6.8 (7.1) points (95% CI, –10.4 to –3.1; P = .001). These changes were observed in patients with and without GBA1 mutations."
These results are not comparable because there was no placebo control in the Ambroxol trial. On the other hand the exenatide improvement was modest and there were serious adverse events, although they were said not to be due to treatment. There were no serious adverse events recorded in the Ambroxol trial.
Personally I would go with the Ambroxol due to the lower risk, easier dosing, and the potential for better improvement.
Thank you for the direct comparison and your opinion Park Bear. It is a discussion of this sort that helps me best evaluate and decide. I’m thinking the same, Ambroxol. I’m concerned about how it will effect my gut biome and can find no info on that. I will revisit the discussion for a refresh. Thank you Park Bear.
Im a bit confused. Option 4 was 'nothing' (which i interpret as none of the above) which is where i would think you would land (it was only in the post title and not the body text).
I do not understand the option 4 reference. Be that as it may, I have it on my agenda to try ambroxol when I get a chance. I am preoccupied with some other matters at this time.
I would take NAC and mannitol if I were you, as well as azilect.I’ve taken them since diagnoses at age 52 (5 years ago) and I seem to be doing a bit better than some people with the exception of the recent freezing and falling on the tennis court.
My work and kids still do not know I have PD, although I think it will become more apparent soon due to dodgy balance.
Exanatide looks very interesting. How are you blood sugars when you do a fasting blood test?
I think it’s worth a try. Smokers have a much lower incidence of Parkinson’s, and azilect acts in the same way.If you don’t get any negative side effects there’s not much to lose.
Very interesting that it acts in the same way as smoking. I will look in to that. Increased coffee intake is good too oddly enough. Rutgers has info on it.
The reason trials are conducted is to find answers to those questions. Nobody knows the answer however well meaning their comments based on their experience.It is not the case that the trial is just a tedious time consuming delay before allowing you to use a slam-dunk helpful pharmaceutical
The isradipine trial would be a good recent example of a "sure thing" that failed after 3 years at phase 3.
At least if you participate in the trial you can be sure you contribute something of value. May you'll get lucky and be on the drug and it will work
I take it you've had the Dat scan and results by now. How was it?
I wouldn't worry too much about safety with Exenatide. It has been used by millions for Type II diabetes. Myself, I was on it for five years until my Type II went into remission. Interestingly -- you have seen those commercials for similar Type II drugs that say you may lose a little weight -- I lost 50 pounds in 50 weeks on Exenatide painlessly. Too bad I had another 50 to go at that point.
I read about the trials when first diagnosed with PD. You remind me it may be time for me to start looking for a physician that will give it to me off label or for something else.
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Bydureon, a repurposed Type 2 Diabetes drug is now in third-stage trials in UK for stopping Parkinson’s in its tracks — results expected 2023. Testing — mice, open label, double blind — has been going on for 10 years and it has been positive every time.
According to a very sensitive test, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), 2/3 of Parkinson’s patients are supposed to be insulin resistant. I read somewhere that IR may be treated with Bydureon (Exanatide) but I can’t now find the link. Just something that might get us one step closer to Bydureon.
Since I read these trials a year has been lost because of COVID. Now results expected by 2024. Funding already done -- trials will proceed. I encourage you to seek out Bydureon (Exenatide -- once weekly) which I have been remiss about getting around too.
All subjects who got drug in earlier trials either stopped progression of slightly improved. The new trial is for 200 people for two years. The earlier trials and the fact that it is a repurposed drug with massive distribution should have the medical profession unhesitating to prescribe it if you ask me.
"All subjects who got drug in earlier trials either stopped progression of slightly improved."
This does not appear to be correct.
"At 60 weeks, off-medication scores on part 3 of the MDS-UPDRS had improved by 1·0 points (95% CI -2·6 to 0·7) in the exenatide group and worsened by 2·1 points (-0·6 to 4·8) in the placebo group"
The 0.7 value tells us that at least some people in the ex group continued to progress.
S Stott also wrote, and i suspect he did so having read the post hoc analysis which is sadly behind a paywall:
"Of the trial participants who were randomly assigned to the exenatide treatment group, only 45% (14/32) of the subjects had an improvement of their motor score (according to the MDS-UPDRS Part 3) of at least 3.25 points at the 48 weeks time point. These individuals were classified as “high responders”.
But some of the other participants in the exenatide treatment group had little or no response to exenatide."
I agree that its encouraging: some number of people (probably 20 something, as an educated punt given the data we have) out of 31 did better the placebo group. But evidently some did not.
my advice is to add a little ldopa to the b1 and nothing else, you will feel "almost normal" for about ten years, meanwhile you will have time to do some sport and try things without the "we will all die" anxiety.
Exenatide or the other glp-1 products that are currently being tested are the most promising area of research at the moment. A very common side effect is initial weight loss when you first take it so add a few pounds to your body weight before you take it.
I'm not convinced by ambroxol at all. The current trial evidence is weak and the science behind taking it is based on it working if you have a gba mutation which is pretty rare. The Dosage is also extremely high which has almost zero testing at that level.
As someone also said, there is a decent amount of evidence that nac is beneficial. There has been 3 phase 2 trials of it including placebo based ones which have been positive so start taking that if you're not already.
I did not know about the NAC trials. I’m taking it. Just heard today it’s best to take at night. High Intensity Health on YT just posted a video about it.
For Ambroxol, you do not need to have the GBA mutation although that was initially thought.
What I mean is that all the preclinical studies that got the human study approved was based on gba research. The trial was tiny and not double blinded so no assumptions can really be taken from it other than it seems to be safe at the Dosage and that maybe just maybe it might have some effect.
My choice will be Ambroxol. The reason is that Ambroxol has been used for many years without any safety issues. I am unable to find it in my country, otherwise I would have started it.
Bydureon is much less scary to me. It just mimics the actions of a hormone that is in your body already: slows digestion (good for Type II), increases insulin output and decreases glucose (if I remember it all correctly). More natural.
Bydureon is the brand name for exanatide once weekly injection and was used in the phase 2 ucl exanatide trial and is due to be used in the phase 3 trial.Actually, since astrazeneca have ceased production of bydureon they will have to use bydureon bcize, assuming AZ can solve their production problems
Bydureon is not cheap, even if you can get an off label prescription. And how does it work? Like red light therapy it is best for non motor symptoms. Like red light therapy it is thought to rescue mitochondria and have anti-inflammatory properties, improve energy production, and switch on cell survival signals.
Parkinson's disease is complicated. But maybe a fairly simple model of it works. There is broadly the disease process, which directly causes all the non motor stuff, and also destroys irreparably dopamine neurons, which in turn causes the motor problems. If you consider that model, you can maybe affect the process and (say) rescue the mitochondria by taking bydureon, or wrigas brocoli tea, or with FMT or with red lights. It is not necessarily the case that you will cumulatively rescue the mitochondria a bit more by doing more than one of them
I understand the urgency you feel, but a bit of personal experience suggests it helps to take a few deep breaths.
In the UK I could talk about corporal Jones of Dad's army, but I guess in the USA you wouldn't get the joke
Results from this phase 2 clinical trial of exenatide were published in August 2017. The initial analysis showed positive signs that exenatide may slow the progression of Parkinson's, but the researchers found the treatment had no significant effects on non-motor symptoms and quality of life.However, this latest analysis, which focused only on symptoms related to mood, suggests that exenatide may improve mood, apathy and emotional-wellbeing when compared to a placebo treatment.
The early trials found more benefits for non motor symptoms. The phase 2 was a bit wooly in truth, with results only a little better than placebo.
The placebo group at 60 weeks were only 2 updrs points worse than at baseline. Normal would be 8 or 9 points. As so often with PD research that's one heck of a placebo effect and makes placebo the number 1 currently available Treatment for slowing PD progression
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