New Hope: It looks like we have something... - Cure Parkinson's

Cure Parkinson's

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New Hope

Eliza-Jane profile image

It looks like we have something positive.

"A new therapy that appears to stop Parkinson’s disease “in its tracks” will begin phase-one clinical trials in humans next year.

The therapy, developed by researchers at the University of Queensland – and partly under-written by the Michael J Fox Foundation – is a world first because it stops the death of brain cells in Parkinson’s sufferers rather than managing symptoms.

If human trials echo the stunning results in animal testing, the inflammation of the brain that causes so much of the progressive damage in Parkinson’s disease (PD) could be halted by taking a single pill each day.

UQ Faculty of Medicine researcher Associate Professor Trent Woodruff said the key to the new therapy is a small molecule, MCC950 – a compound developed and abandoned 10 years ago by a big pharma company that didn’t understand how it actually worked.

At that stage, though, inflammation in the Parkinson’s brain was less well understood.

Parkinson’s disease, said Dr Woodruff, is characterised by the loss of brain cells that produce dopamine, a chemical that co-ordinates motor control – and it’s the loss of dopamine that has been the focus of treatment. But it is also accompanied by this chronic inflammation that occurs as an immune response gone haywire.

It works like this: Inflammation is activated in our cells by complex proteins called inflammasomes. About five years ago, Dr Woodruff and his team found that the immune system causes the NLRP3 inflammasome to light up in Parkinson’s patients, with signals found in the brain and even in the blood.

They then found that the tiny molecule MCC950, given orally once a day, in experiments with mice, “blocked NLRP3 activation in the brain and prevented the loss of brain cells, resulting in markedly improved motor function”.

UQ Institute for Molecular Bioscience researcher Professor Matt Cooper – who initially experimented with MCC950 in the treatment of an auto-inflammatory disease called Muckle-Wells syndrome that can cause deafness and kidney failure – said drug companies had traditionally tried to treat neurodegenerative disorders by blocking neurotoxic proteins that build up in the brain and cause disease.

“We have taken an alternative approach by focusing on immune cells in the brain called microglia that can clear these toxic proteins,” he said.

“With diseases of ageing such as Parkinson’s, our immune system can become over-activated, with microglia causing inflammation and damage to the brain.”

The NLRP3 inflammasome (green) is expressed by immune cells (red) in the brains of people with Parkinson’s disease. Photo: University of Queensland

He said MCC950 effectively “cooled the brains on fire”, turning down microglial inflammatory activity, and allowing neurones to function normally.

This was achieved with three different models of Parkinson’s on mice. It took a further two years of tests in order to convince the editors of the prestigious journal Science Translational Medicine of the efficacy of treatment. The researchers’ paper was published on October 31.

The progress of MCC950 to market appears to be happening rather quickly. Both the Michael J Fox Foundation for Parkinson’s Research and the Ireland-based drug company Inflazome are keen for human trials to start as soon as possible.

Dr Woodruff said much of the preclinical work was already completed.

The biggest hurdle, apart from funding, is that MCC950 came off a patent. This means the researchers have had to develop variations of the original drug for intellectual property reasons. Those new drugs are currently being tested and, according to Dr Woodruff, proving to be even more effective.

There are 10 million people with Parkinson’s disease worldwide. They still have a few years to wait and see if the magic in the lab can be replicated in people.

The phase-one tests next year will determine whether or not the drug is safe in healthy people. All going well, volunteers with Parkinson’s will be recruited for phase-two testing in 2020.

Whether Michael J Fox himself will be one of those volunteers is not yet known."

9 Replies

Good to see that something positive is happening and possibly within reach fairly soon, if it actually proves to be effective and not have ugly side effects!

Thank you Eliza-Jane for reprinting the article that appeared a day or two ago in The New Daily published in Australia. There are 5 other articles about MCC950 in PARKINSONS ONLINE (database of all internet available information on Parkinsons):

Jan 2016 "Blocking inflammasome-induced neuroinflammation in PD . . ."

Oct 2016 "MCC950 - a potential therapeutic for NLRP3-associated syndromes . .

Jan 2017 "NLRP3 and Pyrin inflammasomes Implications in pathophysiology "

Sep 2017 "New AD target: silencing the LRP3 inflammasome with Boron ? . . .

Nov 2018 "For Parkinsons specific protein complex Potential Therapeutic Target

Here is a video clip that accompanies the article in The New Daily :

youtube.com/watch?time_cont...

Contrary to the impression created in the article, this University in Australia is not alone in working with this drug, nor has "interest been dropped" by others. Oxford, for example, is working with it. Starting clinical trials in 2020 means we (or others) are likely to see it available by 2030, assuming it proves to be efficacious. Truth is I hate appearing to be a "nattering nabob of negativism" . . . . but I've been around this rodeo for some time.

Every December Michael J. Fox Foundation does a Webinar on where PD Research is headed each year. Since they are in control of most research funding Its worth a watch. Researchers world-wide are hard at work.

Eliza-Jane profile image
Eliza-Jane in reply to FMundo

Thanks for your reply FMundo, although you rained on my parade. 😥

I felt better thinking something was on the horizon so I will hold that thought. I will continue to feel optimistic as I don't like the alternative. I will check out Parkinson's Online.

ElliotGreen profile image
ElliotGreen in reply to FMundo

Hi,

Could you please post a link to the Parkinson's Online database that you mentioned? I can't find it. Thanks!

FMundo profile image
FMundo in reply to ElliotGreen

Hi,

Unfortunlately it's not possible to simply send you a link, you need to download a free program called Evernote to your computer and then you can access PARKINSON'S ONLINE. The database, which resides in the cloud, currently has 2, 800+ items all Related to Parkinson's indexed into 200+ subjects. Basically I've built it over the past three years. If you have interest I''ll send you an Operator's Manual if you send me your email. Frank.mundo@gmail.com.

We hear so often about dug trials, which get us all excited, but I have yet to hear about a drug that actually stops the progression of Pd. As it takes up to ten years for drugs to make it to the market and we mere mortals don't remember what was put on trial ten years ago, this appears to be something that will never happen.

Why not work on something that really stops the progression of Pd?

Thank god. I don't want to get my hopes up but they are already SKY HIGH!

Does it really bother anyone else that trials are not being run right now on MCC950 itself? FMundo stated above that researchers at Oxford are working on it, but there are no trials listed in ClinicalTrials.gov on it - and the scope of the database is global.

So there's CliniCrowd for nutriments / natural products / supplements, but what about something for off-patent drugs? I have to say, I find this situation rather upsetting.

Speaking of natural products / supplements, I've been having a flare-up in my joint pain and inflammation, probably due to having a bad copy of the Familial Mediterranean fever gene - a mutation in the gene for pyrin which can cause uncontrolled NLRP3 activation. I was trying to figure out why I'm having a flare-up and realized that I had not been taking vitex since I ran out (waiting for delivery); I take it to regulate my menstrual cycle. Apparently, it also acts on NLRP3. Other supplements better known for controlling NLRP3 activation are feverfew (parthenolide) and luteolin.

Are they as good as MCC950 appears to be? Probably not, or we'd have heard about them being useful for PD or other neurodegenerative diseases already; it seems there are often bioavailability and blood-brain barrier issues with natural products (to be fair, the BBB thing is often a problem for synthetic drugs, too).

Yeah, it bothers me.

(I found this post again searching HU/PM for posts discussing microglia.)

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