Artificial Enzyme May Be First Step Toward Treatment for Parkinson’s Disease

[Sapeye2020]

Wow, if this works.....

neurosciencenews.com/artifi...

[parkie13]

Thank you for posting. I for one believe it is a viral, slow moving infection. And look at the similarities in loss of smell and taste in covid-19 and Parkinson's.

[WinnieThePoo]

Alpha synuclein as culprit seems to be on a roll again

[glenandgerry in reply to WinnieThePoo]

You don't sound convinced Winnie?

[WinnieThePoo in reply to glenandgerry]

On the contrary. I still think the SPARK trial is going to have a positive outcome. Alpha synuclein is still a probable candidate for disease cause. I am sitting waiting for my week 100 perfusion as I write this

[redhawk1 in reply to WinnieThePoo]

Hello Winnie . . . do you feel infusions are helping? Any change you can recognize in PD symptoms? Are you going to continue with trial after two years?

[WinnieThePoo in reply to redhawk1]

Hard to say. I feel really good this week. But sifrol titration has stabilized and I have stopped B1 again, which was aggravating tremor. Hard to know how it would have developed. But i get a feeling there are good feelings about the trial. And the pendulum seems to have swung back to A syn being involved in the pathology.Unfortunately I don't think we are going to get the opportunity to continue with the trial.

[redhawk1 in reply to WinnieThePoo]

Well, Winnie, a lot of time and money has been poured into the idea that A -syn is a major culprit in PD! However, i also think the disposal of the misfolded a-syn and such may be just as big.

At the trial center i attend they are also sponsoring the Denali Therapeutics D 151 drug as well! As I understand it this medication speeds up autophagy of that waste. Anyhow, the five people in the phase 1 trial have felt very positive results! Biogen must have seen something very good to invest 1/2 to 1 billion in Denali!! Stock has tripled in the last few months!!!

[WinnieThePoo in reply to redhawk1]

For sure Biogen are investing heavily in this area. D151 is one to watch. Of direct interest to me, the SPARK trial (In which Biogen have invested equally substantial sums) is of an antibody which has proved effective in vitro, mice and humans in general metabolism. The study effectively asked "can it cross the blood brain barrier at an effective dose, AND is A-syn the culprit"?

If as this topic implies, A-syn misfolding is the cause, AND its transmission via the vagus nerve is responsible for the spread in the brain AND controlling mis-folded A-syn in the gut prevents disease effects in the brain...

(Some pretty big "IF's")

THEN - a monoclonal antibody which binds to mis-folded A-syn in the general metabolism including the gut, like BIIB054 (Cinpanemab) is likely to be another candidate for a therapy - regardless of how little crosses the BBB

I feel that following a period in which the pendulum seemed to be swinging to A-syn as artefact rather than pathogen, recently the pendulum has swung back the other way.

SPARK is due to publish findings Q2 2021. And Biogen have accelerated development of Aducanumab

Let's hope there are some useful developments sooner rather than later

[redhawk1 in reply to WinnieThePoo]

In regards to the Roche / Prothena trial . . . the phase 2b I am in may last up to 5 years! So, apparently, “overnight” results are not expected.

And, I think Biogen may see their monoclonal antibody working in tandem with the DNL151!

[Astra7 in reply to WinnieThePoo]

What is in the transfusion?

[WinnieThePoo in reply to Astra7]

BIIB045- and the french "perfusion" translates to "infusion" - it's an hour long intravenous drip

[jeffmayer]

I can't ever imagine being cured got used to the daily battle if it works wow amazing

[MarionP]

Truly amazing potential here.

[Despe in reply to MarionP]

When would it come to fruition, that is the question!

[Sapeye2020 in reply to Despe]

When and if they can pull off the second part of the Hypothesis I would believe based on the last paragraph of the article:

“We know that the nanoenzymes work when injected directly into the brain,” says Mao. “Now, we’d like to see if the nanoenzymes can block the disease progression induced by pathogenic alpha-synuclein traveling from the gut, across the blood-brain barrier and into the brain.”

NOTE: It appears that this group believes that

a-syn goes Gut > to blood > Brain ,

not the reverse ,as others proffer.

That may settle that puzzle.

[rescuema in reply to Sapeye2020]

The relevant backdrop for the gut->brain hypothesis, but it ultimately comes down to protein/detox dysregulation that comes with age-related decline.

parkinsonsnewstoday.com/202....

[Sapeye2020 in reply to rescuema]

Looks like this next step is almost the same experiment in your link , but to show the method of transport of a-Syn is it the blood or the vagus nerve.... Or maybe there are 2 ways for misfolded a-Syn can travel?

[rescuema in reply to Sapeye2020]

This should answer that, at least for the a-synuclein of gut origin -

"Upon examination at seven months, the researchers found that mice with severed vagus nerves showed none of the signs of cell death found in mice with intact vagus nerves. The severed nerve appeared to halt the misfolded protein's advances"

technologynetworks.com/neur...

[Sapeye2020 in reply to rescuema]

So right. And if there is no signs of a-Syn clumping it means that their PtCu nanozyme has cleaned-up all the ROS and other oxidative ? things ? or does the nanozyme wear down over time?

[rescuema in reply to Sapeye2020]

That's a good question. ROS has its own critical functions in normal physiology but it becomes problematic when antioxidants such as SOD, catalase, and glutathione fail to kick in against oxidative damage when it gets too high. The question is how well the foreign synthetic enzyme will be able to contribute to optimal homeostasis without overcompensating.

[Williemom]

Amen. Wouldn’t this be wonderful. It’s good to know research is going on. Our daughter has PD and I’m always telling her there is HOPE!