Irish drug cures Parkinson’s in mice, gets Michael J. Fox backing

[MBAnderson]

This has probably been posted.

irishcentral.com/news/dubli...

Still, it's a long way from there to here.

[ion_ion]

it does not give too much details how it cured the PD in mice.

[WinnieThePoo]

Isn't this yet again the famous Ozzie"stops Parkinson's disease in its tracks" again?

google.com/url?sa=t&source=...

[MBAnderson in reply to WinnieThePoo]

Yes, the news media has a self-interest in hyping the results as does the sponsor of the trial.

Honestly, I don't know why I posted it. This drug has a one in 1,000 chance of making it.

Normally, I don't pay attention to any trials anymore unless they've completed a phase II trial in humans, is compelling and unless I can have a compounding pharmacy make it -- otherwise I'm not much interested in anything more than 2 years out.

Too many false alarms.

If it deserves attention, I'll learn of it before it goes to market anyway.

[WinnieThePoo in reply to MBAnderson]

Chin up Mark. I am interested in this drug, and whilst it has a long way to go I'm just amused how it keeps turning up as news in a slightly different guise. It's groundhog day. There's another thread barely 2 days old about it completing a successful phase 1. As i commented on that one it could launch after a thorough phase 2 but that's got to be a 4year wait. Still good to have things in the pipe

[MBAnderson in reply to WinnieThePoo]

True enough, more so those who have time and less so for those who have less time. 10 years in, I want to know what can help me NOW.

[WinnieThePoo in reply to MBAnderson]

So any joy with the inhaler?

[MBAnderson in reply to WinnieThePoo]

inhaler?

[WinnieThePoo in reply to MBAnderson]

We discussed you not benefiting from dopamine meds maybe due to gut bacteria and I suggested you try the new inhaler as it bypasses the gut for dopamine delivery

[MBAnderson in reply to WinnieThePoo]

Oh, right. Excuse me, I have PD. I made an appointment with my neurologist at the VA for this week for just that, so I haven't started yet.

[MBAnderson in reply to WinnieThePoo]

I saw my neurologist Wednesday I'm going to take a pass on the inhaler. It's pure levodopa, i.e., no carbidopa. I'm not interested in straight levodopa.

[WinnieThePoo in reply to MBAnderson]

I'm not sure I follow your logic regarding pure levadopa. Parkinsons Movement, in HealthUnlocked is the land of pure levadopa in the form of the great god Mucuna...

Despe apparantly obtains generic carbidopa for her husband, so you could look at that route depending on the exact reason for your concern(I can't find any sources of generic Carbidopa in Europe - but apparently it exists in the USA)

However, I suspect your decision rests on a different interpretation of the adverse consequences of levadopa to mine.

Just so we're on the same hymn sheet there are broadly 3 issues on my radar. (Started with 2, and then like a Monty Python sketch , started climbing)

1) (the newbie) is possible interference in the microbiome - but I always assumed that applied to ingested due to presence of the basic compound in the gut with food - rather than impacting the microbiome from the bloodstream of the gut.

2) Nausea - caused by high pure levadopa levels in the bloodstream - carbidopa or benserazide (or vitamin C, green tea and doubtless others) help prevent this breakdown of levadopa into dopamine outside the BBB

3) Dyskenesias (+other suggested neurodegeneration issues) caused by prolonged / excessive / unbalanced levadopa doses in the brain (and conversion to dopamine there). It's mainly, I thought, the converted surplus dopamine which is the issue.

Broadly, I assume from your profile, your concern is with No3. But Carbidopa really doesn't impact that. Carbidopa only exists outside the BBB (it can't cross it) and prevents LD being converted (decarboxlated) outside the brain, leaving more of the total administered LD to cross the BBB and be converted to dopamine there.

I realise that the inhalers intended use is as a "gap plug" between LC doses, but worst that could happen without the carbidopa "sandwich" is it won't work very well. (Dose in inhaler too small at permitted levels to get sufficient LD to the brain to be of much use, without a decarb inhibitor to prevent decarboxylation of the inhaled levadopa)

Did your neurologist suggest the lack of Carbidopa was an issue, and if so, did he further explain why?

[MBAnderson in reply to WinnieThePoo]

Winnie,

Boiled down, it was number 3.

I'm not yet convinced levodopa metabolites and carbidopa are not damaging to a degree which might aggravate symptoms or progression. With my feeble understanding as it is now, I give it about a 70/30 that it doesn't.

I didn't understand that it's intended use is to cover off periods and I don't have off periods because I don't take C/L on a regular basis.

I am more resistant to levodopa therapy, perhaps, than many because, for one thing, most of the time, it does nothing for me - which concerns me, because that might mean when I finally need it on a daily basis, I might need higher doses. What are your thoughts on that? I am thinking that when I'm finally ready for daily therapy, I would look into the duo pump if it allows for a 'starter' dose.

Marc

[WinnieThePoo in reply to MBAnderson]

Hope the FUS goes well. I think it makes sense to focus on that. Karen Raphael has been on Sinemet for more than 8 years, and doesn't imply delaying initiation has any benefit, in her interview

I remain a bit confused about why you rejected the inhaler because it DIDNT contain Carbidopa. The No3 issues are almost certainly (read - certainly) due to levadopa and not Carbidopa. Carbidopa can't cross the BBB so is never in the brain. It just lets more Levadopa get there, and so reduces the side effects that decarboxylation of levadopa OUTSIDE the brain causes. But Carbidopa offers no protection for the No3's - quite the opposite. If those troubles are due to levadopa supplied to the brain - Carbidopa increases the amount of levadopa in the brain.

And the idea with the inhaler was not to plug the gaps (which I appreciate is its purpose). I knew you didn't take C/L. It was in response to your comment that maybe the reason you didn't respond to C/L therapy was poor absorption of Levadopa due to breakdown by bacteria in your microbiome. IF that were the cause, THEN the inhaler offered a route for getting levadopa into the blood and hence the brain, that couldn't be confounded by gut bacteria.

Or it maybe is NOT a problem with gut bacteria. It may be like Karen Raphael

"However, when I was diagnosed at 55, my PD was probably more advanced than most who first get diagnosed. I had to take far more than the normal amount of levodopa to get myself back to an acceptable level. "

But finger crossed the FUS will make an important difference to you, and like you say, it makes sense to focus on that at this stage. I am doing likewise with SPARK.

[MBAnderson in reply to WinnieThePoo]

Thank you for reminding me the purpose was absorption, which escaped me during my visit, so I'm going to call my neurologist back and revisit the issue with him.

Perhaps the 'no reason to delay initiation' school of thought is because of their belief (as per the sub-Saharan African study or whatever) that it is the ever-increasing dose and not the duration that induces dyskinesia. Even if that is true, the logic totally escapes me.

Since there is no shortage of studies which conclude the opposite and since studies do not apply to every person, I believe we would all concede that some people have gotten dyskinesia without a dose increase, so the question becomes, what percent will that happen to? Even if it's only 10% to 20%, that would justify delaying therapy, for me, because once a person is wrestling with dyskinesia, there is no going back, i.e., there is only the struggle as to how to reduce the dose.

Why not take as long as possible to get to that point?

Perhaps 1 of the more important surveys we could do among ourselves on this forum would be to ask people to describe their experience with dyskinesia, i.e., at what duration and dose it occurred.

I just took a call from the FUS people and they want to schedule me 2 weeks hence. Oh God, what have I done? I'm going allow someone to heat up the center my brain!!

Marc

[JAS9]

OK, check me on this. First, here's an article with a much fuller explanation of what might be going on: parkinsonsnewstoday.com/201...

Next, here's a quote from that article:

"The NLRP3 inflammasome is a multiprotein complex believed to drive chronic inflammation in Parkinson’s and other neurodegenerative diseases. A recent study in postmortem brains from Parkinson’s patients and mouse models of the disease showed that this inflammasome is activated by aggregated alpha-synuclein, the main component of Lewy bodies, and loss of dopamine-producing nerve cells. Both Lewy bodies and death of dopaminergic neurons are hallmarks of Parkinson’s.

Then, the researchers found that MCC950, an oral small-molecule blocker of the NLRP3 inflammasome, completely suppressed inflammasome activation in microglia, a key cell type in immune responses in the central nervous system (brain and spinal cord). MCC950 also inhibited alpha-synuclein clumping, prevented the loss of nerve cells, and eased motor deficits in a mouse model of Parkinson’s disease."

Finally, I went in search of MCC950 and found many sources. This is not a brand new discovery that makes it impossible to find. Inflazome isn't the only company on this track. MJFF is funding their development of a "tracer" device that will let them check the level of inflammation non-invasively. This should speed up testing.

Now, we all know how this works with other drugs; the big pharma won't touch something found in nature unless they can modify it slightly and patent that. Otherwise there's nobody to fund the studies.

But what's stopping someone from getting hold of MCC950 and trying an off-the-books test of their own? I'm not saying that I would: there are tons of unknowns. Still, if someone was desperate enough, what would stop them?

Just one of many sources: tocris.com/products/crid3-s...

Another source with more info: invivogen.com/mcc950?gclid=...

[JAS9 in reply to JAS9]

This article describes Inflazome's approach and what they're hoping for:

endpts.com/novartis-backed-...

This sums it up: "tough conditions like Parkinson’s and Alzheimer’s, where tamping down on longterm inflammation could pay solid benefits over time... Like his biotech rivals — a group that includes NodThera and IFM — Cooper is pursuing the belief that rather than tackling the entire IL-1 beta pathway, it’s possible to much more safely single out the “lone wolf” that they believe is the prime suspect for the laundry list of conditions it may trigger."

[WinnieThePoo in reply to JAS9]

No. We know all this. Groundhog day. There are earlier threads, links to a video news feature, john pepper sharing his wisdom that it is designed to fail because the pharma industry only exists to ensure he has a chronic illness...

The new story is the phase 1 trial. It IS interesting. It's just that it regularly pops up as new, when in fact the sites servers must be 50% filled with old threads about it

[WinnieThePoo]

healthunlocked.com/parkinso... was the original post

[JAS9 in reply to WinnieThePoo]

OK, I've gone over that entire discussion and I don't see an answer to my main question: Given that MCC950 is available from many sources (albeit for experimental use), what's stopping someone who's desperate from getting hold of some and experimenting on themselves?

To repeat myself again: I wouldn't do it - not yet; there are many unanswered questions and I'm not desperate enough. Also, it seems that things are finally ready to begin to start to move forward with one of these slightly modified molecules, so I'll wait. But I might not be willing to wait another 4 years.

[WinnieThePoo in reply to JAS9]

I think you'll find as a punter it's not as easy to get hold of as you imagine. And as for the urgency, believe me,as someone with PD myself I understand the frustration. But I remember thalidomide too