2021 Should be An Informative Year

[jimcaster]

Parkinson’s disease research has ended in numerous dead ends despite substantial efforts over many years. Recently, Biogen and Sanofi scrapped their Parkinson’s candidates, cipanemab and venglustat respectively, owing to lack of efficacy, and a disease-modifying therapy has yet to materialise.

But the push to find drugs that help beyond reducing symptoms continues, and Evaluate Vantage has delved into the pipeline of projects in active late-stage clinical trials. This year is shaping up to be crucial for the field, with 10 studies expected to yield data or to complete in 2021.

One target that crops up multiple times is GLP-1; this approach, traditionally employed in type 2 diabetes, is also being tested in Alzheimer’s. Among other avenues of research, it is hoped that gene therapy could offer a one-time cure for Parkinson’s.

evaluate.com/vantage/articl...

[Hidden]

4 of the 19 trials are Exenatide. There is a lot of hope and money invested in Exanatide.

[pdpatient in reply to Hidden]

@cclemonade, sorry to cast some Coldwater on your enthusiasm and hope for a second time today 🤨

I have been on Exenatide since 2006 and I personally don't think it would have made a difference. I got Parkinson's anyways and it didn't do much to help with my symptoms which is tremor dominant.

RKM

[Hidden in reply to pdpatient]

I did not say I have a lot of hope and money in Exenatide. I said there IS a lot of hope and money in Exenatide. Big destinction.

[WinnieThePoo in reply to Hidden]

It's a disease modifier not a symptom reliever. It might be that with exanatide it takes 20 years to progress to stage 3 instead of the 10. I'd take that as a good start.

[pdpatient in reply to WinnieThePoo]

@winniethepoo, you perhaps do have a point. My diagnosis symptoms have not progressed over nearly 10 years and come to think of it, it is certainly possible.

RKM

[Hidden in reply to pdpatient]

Your symptoms have not progressed for nearly 10 years and you are on Exenatide. I doubt that is a coincidence. I’m perplexed then by your stating that it didn’t do much to help.

[WinnieThePoo in reply to pdpatient]

Exanatide is being trialed as a disease modifier. Something which slows the rate at which your parkinson's progresses. Why would you expect it to do anything for your existing symptoms?

[pdpatient in reply to WinnieThePoo]

@winniethepoo. Your point well taken. Never viewed my plight / fortune with this perspective. However, your position speculates that disease modification and symptoms are synonymous with each other and one is indicative of the other. At least that is the way, I have seen most research being presented or perceived.

RKM

[WinnieThePoo in reply to pdpatient]

I think the way trials like the exanatide one (or my SPARK trial) measure disease progression is to look at symptoms over time, and compare the rate at which symptoms progress (off meds)

Initially it is hard to be sure whether the symptomatic result is due to the drug relieving the symptom or the drug "putting out the fire" that causes the symptoms to get worse.

There are 2 ways of trying to isolate the disease modifying / progression slowing effect from simple symptomatic relief

"Wash out" - after (say) 12 months drug use, stop drug use at month 12 and observe the symptom at month 12 and (say) month 15. If the benefit remains at month 15 it is likely it is due to the disease slowing properties rather than simple symptomatic relief. If you stopped Sinemet on month 12 and assessed symptoms at month 15 - they would be much worse

The 2nd method is to review at multiple points. If you measure the symptom at month 12 and month 24 and the result remains constant, then it is likely to be a progression slowing effect. Especially when you consider the measurement is off-meds (No sinemet, pramipexole etc for 24 hours before the assessment)

[Hidden in reply to WinnieThePoo]

Well said. Thank you.

[bassofspades]

Genomic therapy in 5...4...3....2.....

[Hidden in reply to bassofspades]

Bass of Spades, your upbeat attitude is wonderful and very healthy! Along the path to genomic therapy I foresee a disease slowing treatment of some sort and stem cells and FUS.

[bassofspades in reply to Hidden]

The thing with stem cells is that it doesn't stop the disease process, so those replaced cells might feel good for a while but they eventually die back from the same things as the old ones.

Gene therapy will target the specific defects, in protein synthesis for example. New methods in gene mapping will allow us to see exactly where things are going wrong and target the specific areas of the genome. Cancers will be cured like you've never imagined, too! They're already having success with things like sickle cell anemia and beta thalassemia, which are rare blood disorders. Just trust me , it's totally do-able and it's coming!

[kevowpd in reply to bassofspades]

Will this gene therapy help those that have already lost <70% of their dopamine transporters?

[bassofspades in reply to kevowpd]

I hope so ! That's all of us!

[kevowpd in reply to bassofspades]

Conceptually, I'm not sure why fixing up my genes will help with the damage already done. But i have to confess to knowing absolutely nothing about it.

As for the theories about transplanting new cells into a hostile environment, I'm not convinced that its futile. The death of dopamine transporters is actually fairly slow. If we say you start with 1m DTs, and wr accept the 10 year / 70% estimates, then you lose 7% or 70,000 every year. If you can load up on another 500,000, then that might buy you another 500,000/70,000=7 years.

[Hidden in reply to kevowpd]

A study done in Lund Sweden in the 80’s, proved that the implanted neurons lived and were effective for over 20 years. I am new to understanding the trial process.

Is it reasonable to think that if a stem cell trial is said to take 7 years that in reality it could be 15+ years bc multiple rounds of trials might be necessary? Of course I hope they hit it out of the park in the first go but that seems rather unlikely.

[Hidden in reply to bassofspades]

I understand. But to my knowledge stem cells are farther along and therefore have a greater likelihood of being accessible to us someday. That was my only point. Hopefully I’m wrong. Are there in human trials for gene therapy for PD?

[bassofspades in reply to Hidden]

I dont know of any specific PD trials. All I know is that the supporting technology of that field is growing at an EXPONENTIAL RATE.

[PixelPaul in reply to Hidden]

Assuming that stem cells are proven to be an effective treatment, the problem I see with them is one of scale. It is a highly invasive surgical procedure, and given its current state I don’t see how that realistically scales to the masses.

[Hidden in reply to PixelPaul]

The same can be said of DBS yet it is a viable option for many.

[PalmSprings in reply to bassofspades]

Does gene therapy have potential for those of us with non genetically linked Parkinson’s?

[bassofspades in reply to PalmSprings]

youtu.be/PkukxG6UDvc(Not working as expected?)

The answer is within the first 3 minutes

[PalmSprings in reply to bassofspades]

Thanks, that was super informative and interesting!

[Gioc in reply to PalmSprings]

Hi PalmSprings,

There are various ways to use this discovery, here is a recent one ... and "promising" ... about mice.

nature.com/articles/s41586-...

Here is a more understandable explanation, maybe:

healthdesk.it/ricerca/terap...

[PalmSprings in reply to Gioc]

Thanks, so interesting!

[bassofspades in reply to Gioc]

Yes!!

[MBAnderson]

Thnx. Good info.

[Hidden in reply to MBAnderson]

Hey! What are you doing on here?! Are you in Switzerland?

[MBAnderson in reply to Hidden]

I am. Having my head examined.

[AmyLindy in reply to MBAnderson]

Safe Travels 🇺🇸 🇨🇭 🇺🇸

[MBAnderson in reply to Hidden]

"What am I doing on here?" I am in quarantine with nothing else to do, so you're stuck with me.

[Hidden in reply to MBAnderson]

😁 I’m so glad you are in good spirits Hey, the dog is cute but I miss the baby.

[Canddy]

thank You! Very informative!