Exanatide


#21

Bastyr University are doing (ongoing) research into diet and Parkinson's progression with some interesting results: http://bastyr.edu/news/general-news-home-page/2017/06/bastyr-launches-parkinsons-program

 


#22

2013 to 2017 for a drug already widely used.

Fills those of us on the Parkinson's roller-coaster with no end of confidence.

The lack of funding will stop many a promising therapy reaching the shelves.

Sigh.


#23

Hi TeeHee, 

Exenatide, as well as other diabetes drugs, stimulate the GLP-1 receptors in the pancreas. This causes insulin to be released and so regulates blood sugar levels. 

GLP-1 receptors are also found in the brain, and lab-based experiments have suggested that activating them can boost the function of dopamine connections, have anti-inflammatory properties, improve energy production, and switch on cell survival signals.

At the moment, there is little evidence to suggest that dietary changes can significantly influence Parkinson's symptoms. Eating a balanced diet will improve general wellbeing, and may help people to manage some of their symptoms. 

Hope that helps, 

Annie

Parkinson's UK Research Team 

 


#24

Bastyr published the primary conclusions of their ongoing research earlier this year ...

Materials & Methods:

The goal of this ongoing natural history study is to identify modifiable lifestyle variables associated with rate of PD progression. The Patient-Reported Outcomes in PD (PRO-PD) is the primary outcome measure, ranging from 0 (asymptomatic) to 2500 (severe) to assess PD severity.

Pragmatic Results
After adjusting for age, income, Hoehn & Yahr, and gender, the mean score at diagnosis was 574, with an annual increase of 16 points per year. The FFQ revealed an association between improved outcomes and intake of fresh vegetables, fruits, nuts & seeds, non-fried fish, olive and coconut oil. Canned fruits and vegetables, cheese, ice cream, beef, chicken, and pasta were associated with statistically worse outcomes over time.There was a dose-dependent association between days per week of exercise and reduction in PRO-PD score over time, the benefit becoming statistically significant with three or more days per week. Of the activities listed, yoga was the most beneficial form of exercise. That “other” was also significant suggests individualized programs may also be effective. Supplements used by >10% of participants are listed here. After adjustments for age, income, HY, and gender, fish oil, coenzyme Q10, and vitamin D were the only three supplements to be associated with fewer PD symptoms over time. Iron and melatonin supplementation were associated with faster PD progression. Because poor sleep has been associated with PD progression, an exploratory analyses was performed to differentiate the impact of insomnia from melatonin, a common treatment for insomnia. The association with the melatonin went away after adjusting for insomnia.

CONCLUSIONS:

The foods most protective against PD progression are staples of the Mediterranean diet. While previous studies have linked dairy and beef intake to PD incidence, this is the first study to demonstrate an association between dairy and beef intake and PD progression. Patients should be encouraged to exercise 30 minutes per day for maximum benefit. Whether yoga can be standardized and exploited to slow PD progression deserves further attention. Individuals reporting consistent supplementation with fish oil, coenzyme Q10, and vitamin D have improved outcomes in a naturalistic setting.
This pragmatic natural history study offers the first evidence base for prescribing a Mediterranean diet, daily exercise, and targeted nutritional supplementation to patients with PD.


#25

https://bastyr.edu/news/general-news-home-page/2013/05/unusual-parkinsons-study-seeks-learn-positive-deviants-0

 


#26

With the incredible good results from the clinical phase I and II trials of exenatide, I wonder why I have the feeling that it will still take a very long time before people will get this. I even have the feeling that exenatide will never be given but that we will lose another 20 years in trying to find another drug that works similar to exenatide and we will test it for another 15 years before giving it to people ... all in the name of safety. I mean, safety is good but aren't they exagerating here ? In 2 years of trials nobody had any problem with exenatide. PD patients are taking real crap meds for anxiety and sleep disorders that are really dangerous longterm but they don't seem to care for that. But when it comes to something already being used by people with diabetes for more than a decade, why do we need to test longterm effects in such detail ? PD patients are suffering. They need all the help they can as soon as possible. 


#27

I think we all know it is not about safety...it is about profits and greed.

Exenatide is cheap and out of patent....makers of Parkinson's meds will make sure that it does not get into the lucrative market...

They will bring  new drugs out,probably not as safe or effective, under patent, at vast expense to the NHS and trouser millions.

Like all new drugs, there will be a post-code lottery...we can't have Opicapone in Leeds.

Patient welfare is not really important when profit is their God.

Read Ben Goldacre's 'Bad Pharma'.


#28

Hi Everybody, hope you are all not too bad today.

I share your general concerns about whether Exenatide or other GLP-1 agonists will ever be generally prescribed for PD. It all seems to have gone very quiet since the phase 2 trial results were announced in August 2017. So what is actually happening with regard to a phase 3 trial which I accept is needed? It would be good to hear from PDUK on this topic. Has anyone out there heard anything about a phase 3 trial?

Thanks,

Dave.


#29

Very interesting and promising.....can research give more information about progress..?

Thanks

GG

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31585-4/abstract


#30

But ey, they keep begging people for money to perform their research. I am really done giving money for any kind of medical research. Last time I was approached by someone for cancer funding. I said: "Why would I sponsor that ? If I sponsor it now and 20 years from I get cancer I will probably need to pay 20.000 euro a year for a cure that has been found with my sponsoring. And if I can't pay it then they will let me die.". If this med isn't given to patients, I will stop any PD funding. Because these PD associations that receive funding are as guilty as the greedy pharma industry.


#31

Hi all

We completely agree that it takes too long for people to benefit from research into new medications. That's why our Research Vision is to make new and better treatments available in years not decades. Let's take a look at some of the issues in the pursuit of repurposed drugs.

Why is more research needed?

For exenatide, a phase 3 trial would be needed to establish the drug works and check for any adverse effects in a large number of people. This is particularly important in Parkinson's where people experience very different symptoms. It could be that some people with certain symptoms won't benefit from the treatment, or worse could experience side effects.

Another consideration is how long someone will need to take the drug for. Some drugs may be safe to take short term but have side-effects, or become less effective when taken for longer periods, which would likely be needed to treat Parkinson’s. Drugs may also interact with each other — reducing the effectiveness of other medications or causing unwanted side-effects.

So even approved drugs need to go through the clinical trial process to make sure they are safe for people with Parkinson’s. However, for repurposed drugs, this can be a much quicker process that those developed from scratch. We already know much about these drugs so they may skip earlier stages and move into the later phases of trials more swiftly, and be made available quicker.

So, where are we at with exenatide?

The latest results came last August. There's a brilliant review of where we are so far from Parkinson's researcher Simon Stott https://scienceofparkinsons.com/2017/08/08/exenatide-an-editorial/ and also our blog on these results here https://medium.com/parkinsons-uk/exenatide-latest-trial-results-explained-ef72fbee3c44 if you haven't already seen them. 

But briefly, results so far are looking good and the next stages are being planned. We believe the academics are in discussions with regulators for a phase III study. Like you we are eagerly awaiting more news and, as further research will likely require many more participants, hope to be able to share opportunities to take exenatide by taking part in the trial

But will these drugs ever be made available?

The issue with profitability of repurposed drugs is undoubtedly a major hurled for bringing these often 'off patent' drugs to market (i.e. into the hands of the people who need them). But it's not just an issue for Parkinson's.

We are doing all we can to improve the pathway to making drugs like exenatide available - you can read about how we are working with the Government and other charities to do this in our latest blog post: https://medium.com/parkinsons-uk/making-repurposed-treatments-a-reality-5c811d0b413b

And there has also been progress in speeding up the delivery of new breakthrough treatments: https://www.parkinsons.org.uk/news/fast-track-route-medicines-and-technology-announced

If you would like to help support this kind of activity, I would recommend finding out about our policy and campaigning work. This is a different way you can help support the charity that does not require a financial donation https://www.parkinsons.org.uk/get-involved/campaign

In summary

Despite the hurdles, there are successes in the history of drug repurposing – such as sildenafil, an angina medication developed in 1989 now more commonly known as Viagra, and azidothymidine, which failed as a chemotherapy drug but because a HIV medication in the 1980s. Both industry and academic researchers are devoting more resource in the pursuit of repurposed drugs and progress is being made to help these drugs get to market.

We will continue to do all we can to deliver new and better treatments faster, and, as everything we do is led by people affected by Parkinson's, I hope that you will continue to engage in conversations like these to make sure we are addressing the issues.

With very best wishes for 2018,

Beckie

The Research Team


#32

I understand you have to follow the procedures but I am highly critical of them. Farmers can poison our food with pesticides without decades of testing what will be the effect of pesticide usage on people but when it comes to testing medicines on people decades of testing is needed. Imagine you have ALS and you know you will die in the coming 6 months and there is a treatment being tested in clinical trials that might help you .. why would you prohibit such a person to take it ? Who cares about the longterm side effects. If you take nothing you die in 6 months which is the worst side effect there exists. Makes no sense at all. In case of Exenatide, given the strong results, people with PD all over the world (at least those that want) should be getting treated with it while being very strongly monitored by their doctor. PD is not something like having the flu. PD is a horrible disease that leads to a horrible condition eventually if you don't stop its progression. Maybe if you take Exenatide for 10 years you will have some nasty side effects. But if you take nothing you will suffer from horrible side effects even sooner. At least, that is my view on the matter. 

 


#33

If I may ask a question ... what is the biggest bottleneck for getting these meds approved as fast as possible ? Is it money ? Is it people volunteering ? Regulators ? ...


#34

Hi Mister_X

This is a great question, but unfortunately there is no simple answer or single bottleneck.

More funding is required for Parkinson's research at all stages of the pipeline, but a lack of investment in the later stages of clinical trials, which can cost billions of pounds, is one of the bottlenecks.

This stems from Parkinson's being seen as a complex condition in which to carry our clinical research, partly due to the lack of measurements to monitor its progress. Researchers around the world are actively looking for ways to detect and monitor the progression of the condition, so we can identify drugs that may slow it. At the same time our Critical Path for Parkinson's initiative is smoothing out the path for all future drugs by making clinical trials smarter and faster, and working directly with regulators to do this. We hope that this will encourage future investment in clinical trials for Parkinson's.

Another bottleneck is that while early stage, 'basic' scientific research has increased our understanding of the process inside brain cells that lead to their loss in Parkinson's, this knowledge is not always taken forward into drug development. The Parkinson's Virtual Biotech aims to take the best ideas forward toward clinical trials, so filling this gap.

Finally, recruitment can impact on the success of clinical research, particularly in later stages of trials that require many people to take part. We are engaging with researchers to share participation opportunities and reduce the likelihood that research will fail due to a shortfall of participants.

But as well as quantity, finding the right participants is vital. Researchers are beginning to understand that there are multiple types of Parkinson's, which likely respond to drugs in very different ways. Currently we don't know enough about these possible types of Parkinson's to identify those participants who would benefit from a new therapy and those who would not. This means, when it comes to clinical trials, we are not testing the drugs in the most effective manner. This fact could be responsible for previous Parkinson's clinical trials failing in the late stages.

To combat this, researchers are developing our knowledge of the different types of Parkinson's, and how they respond to drug therapies. At the same time, the Critical Path for Parkinson's aims to improve the way participants are selected for trials to give new therapies the best chance of demonstrating effectiveness. This is essential for trial success, which is necessary for new and better drugs to be made available to the people who need them.

While this is not an exhaustive list, it highlights the complexity of the situation and the progress that is being made to speed up the delivery of new and better treatments. I hope it helps to answer your question.

All the best,
Beckie

The Parkinson's UK Research Team


#35

Thanks for your reply. I have following remarks on them.

  1. You probably heard about Bitcoin, right ? Bitcoin and other cryptocurrencies are a big hype lately. There are even cryptocurrencies used in order to fund scientific projects. To give an example:

https://www.emc2.foundation/

The purpose of this project is to fund general scientific research. Maybe your foundation could launch something similar for parkinson's disease or neurodegenerative diseases. This could help with the lack of funding maybe ?

  1. Are people in your trials doing genetic testing ? With statistics or AI techniques it is possible to identify subgroups for which a certain treatment might have helped, and for which it doesn't.

  2. I was actually a little bit dissapointed with the Exenatide preclinical trials. It was only tested on mice that got poisoned. It was never tested on mice carrying a specific gene mutation related to PD. Wouldn't it be wiser to test all these meds on several mice carrying each a different PD mutation gene so you can design better clinical trials ? In the past this wasn't possible but nowadays it is possible. After reading a lot about PD research if there is 1 thing that I realized it is that poisoning mice is not really imitating the disease and that's why until now science never managed to slow down or stop the disease. At least, that is my opinion. The same is true for Alzheimer where the focus is all concentrated on beta amyloid but the clinical trials according to me only reflect that their focus is completely wrong.

  3. Are you also considering to test the effectiveness of J147 ? Maybe you could work together on this with that research group ? That could also solve the problem of participation because you could do tests in the UK and in the US. Maybe there is a need of research groups to work together.

I am just brainstorming here, not trying to sound like a smartass or anything. I want to avoid that maybe one of my comments is something you didn't thought about but would be helpfull and that you don't do it in the future because I was too scared to mention it. In the end, I just want to help as much as I can in finding a cure, even if my input is limited to donations and posting ideas here.


#36

i was on the exenatide phase 2 trial and i received the placebo. however at the end of the trial i approached my neurologist and requested the drug , as it is a diabetes drug it is classed as off label for pd, anyway i have been using it 2mg injection every week for two years, Is it making a difference? I have no idea. I suppose that another brain scan would reveal any re- population but i have not had any requests to have one and i will bring it up with my nuero next month, I am now on the accordion pill ph3 trial plus i have been assessed for dbs, i have postponed the dbs until i see what difference the accordion pill makes. i will keep you posted


#37

J1347 appears too be derived from turmeric ( circumen). Large body of data on these in PD you can check out. I search on http://europepmc.org/
Peter


#38

This recent study showed that curcumin does benefit the brain. It was tested on a group of 40 people. Memory was boosted with 28 % in 18 months. Curcumin was also able to reduce amyloid accumulation. This amyloid formation is linked with Alzheimers disease. Curcumin’s anti-inflammory effect reduced brain inflammation which is considered as one the driving factors of all neurodegenerative diseases.

The article didn’t say anything about PD. However, this article gives me a very positive outlook about curcumin for PD. First of all, it is anti-inflammatory. From what I have read about neurodegenerative diseases brain inflammation is present in all these diseases and they play an important role in the progression of the diseases. People with PD have brain inflammation so from that respect it looks like this curcumin formulation would also be beneficial for PD patients.

Besides that I also encountered other studies about Curcumin’s interaction with alpha-synuclein, the hallmark of PD:


There is evidence that curcumin interacts with toxic alpha-synuclein clumps decreasing its toxicity which would of course again be positive for PD patients. Besides that the article also states that Curcumin induces neurogenesis. According to this article a huge amount of other possible benefits can be found for curcumin with PD.

The results of the first article I posted can also be found here:

However, in this article they don’t reveal which curcumin formulation was used. They only state that curcumin with a better absorption was used. In the first article they claim they used theracurmin. I don’t know if this is true. I need to look further into this.

Edit:

I found the original research paper: http://www.ajgponline.org/article/S1064-7481(17)30511-0/pdf

They did indeed use theracurcumin in this study. I really think this deserves to be studied as a treatment for PD patients.

Can someone make a separate thread about these findings ? I am not able to make a thread (I don’t know why).


#39

Hi Everybody,

hope you are all not too bad today.
So has anybody heard any news about Exenatide recently? This is one of the most promising areas of research in the last year. It would be good to get some up to date information about a phase 3 trial etc.

Thanks,
Dave.


#40

well as i have posted before, i have been on exenatide since the trial ended, weekly injection. i could not tell if it works or not. i will continue to take it just in case. i am on a trial now for the accordance drug. at the moment i am titrating from stalevo to sinemet then to accordance in a couple of weeks.