Three distinct brain circuits in the thal... - Cure Parkinson's

Cure Parkinson's

21,274 members22,750 posts

Three distinct brain circuits in the thalamus contribute to Parkinson’s symptoms

jackedmonston profile image

Targeting these circuits could offer a new way to reverse motor dysfunction and depression in Parkinson’s patients.

Parkinson’s disease is best-known as a disorder of movement. Patients often experience tremors, loss of balance, difficulty initiating movement. The disease also has lesser-known symptoms that are non-motor, including depression.

In a study of a small region of the thalamus, scientists at the McGoverm Institute at MIT.). identified three distinct circuits that influence the development of both motor and nonmotor symptoms of Parkinson’s. Furthermore, they found that by manipulating these circuits, they could reverse Parkinson’s symptoms in mice.

The findings suggest that those circuits could be good targets for new drugs that could help combat many of the symptoms of Parkinson’s disease, the researchers say.

“We know that the thalamus is important in Parkinson’s disease, but a key question is how can you put together a circuit that that can explain many different things happening in Parkinson’s disease. Understanding different symptoms at a circuit level can help guide us in the development of better therapeutics,” says Guoping Feng, the James W. and Patricia T. Poitras Professor in Brain and Cognitive Sciences at MIT, a member of the Broad Institute of Harvard and MIT, and the associate director of the McGovern Institute.

The Institute was founded by Pat McGovern, Chairman of International Data Corporation (IDG) for whom I worked for nearly 20 years, Pat was a socially reponsible high tech entrepreneur. He built a world-wide high tech publishing company (100 magazines in 70 countries). But IDG is probably best known for the highly successful "For Dummies": books. . Instead of going public, Pat started an employee ownership plan.

17 Replies

Yay! Another cure for mice!

wriga profile image
wriga in reply to stocktiki

Stocktiki, the problem is not mice. This is a research article, done on mice because at a certain level mice brains behave like people's brains. Mice are inexpensive and you can do experiments on them (creating the PD and trying out a therapy). Nobody is allowed to do these experiments on real people. If experiments like these work (on mice) and they enable the researchers to identify a therapy, then the next stage is to run a clinical trial. For a stage 2 trial, the costs are multiplied by about 200 and for a stage 3 trial they are multiplied by about 100,000. Academic researchers cannot afford that, only the Big Pharma companies can. If, as you say, it could lead to a cure (not for mice but for men) then Big Pharma won't touch it, because it would kill their profits. See my other post today

kevowpd profile image
kevowpd in reply to wriga

The revenue from all global CL sales probably wouldnt be material to the books of one of the big 3 or 4 pharmaceutical companies.

Also, didnt coq10 go to phase 3? Someone funded that, no?

wriga profile image
wriga in reply to kevowpd

You may be right for both of your statements, Kevowpd, but a phase 3 that could lead to an approved therapy for PD, given all the symptoms and degrees of progression would involve a very large number of patients. The general principal for Pharma remains the same : "Don't kill the goose that lays the golden eggs"

Slide 16 : "Reflections ..." Breaking stage 2 can stop PD, Pharma profits are at stage 6.
WinnieThePoo profile image
WinnieThePoo in reply to wriga

Utter nonsense. Big pharma make buttons out of the gold standard remedy. We are talking only MSD and they can hardly bother in most markets to try to make a few bucks out of branding. If a cure replaced C/L it would hurt a few small pharmaceutical manufacturers (who are production only operators not involved in research.)Big pharma are investing billions to find a new cure, or significantly better treatment because the profits would be of the type that they look for.

How does your self-pitying paranoid theory of big pharma square with the millions spent (and almost always as a simple loss) on new therapies like monoclonal antibodies, or repurposed drugs like isradipine. Biogen spent over 20 million on BIIB054 - the trial I participated in for a drug to slow progression. Nearly twice that was spent on isradipine.

Note, isradipine was a drug out of patent. Patents are for applications not chemicals. So isradipine as a treatment for PD would have been patentable.

And as for natural substances there are worldwide patents held for ps128 and true niagen.

wriga profile image
wriga in reply to WinnieThePoo

Thanks Richard, at least my post creates a debate. If you think you can write a strong patent to protect the process I am using, then I'm all for it, not to make money but to get the product out to the people that need it in a way that they can use it. That's what I'm trying to do, help others. And please don't call me self-pitying, my PD is now very well controlled. That's not the case for many others. As for the cost for patients, ask Jack.

WinnieThePoo profile image
WinnieThePoo in reply to wriga

I was careful with my language Albert. I played the ball, not the man. It was the proposition that big pharma was a conspiracy to keep pwp suffering for their profit that I described as self pitying.

wriga profile image
wriga in reply to WinnieThePoo

Richard, I recognise that you played the ball, but balls like that leave a hurtful mark, so I sent you a curling ball back. I see that you dodged it, so lets stick to the observations. I also agree that PD drugs should only be worth pennies to big Pharma and it's the small players who are getting most of the pennies. I also agree that it makes no sense to mount a Pharma-wide conspiracy (where A keeps PD territory in exchange for not touching AD territory held by B) just to keep this smallish amount of cash flowing to those in the levodopa business or its repackaged variants.

I know that you have a lot of experience in the Pharma business and I have none. I have tried to find an explanation for the black hole in pharmacological research to address the vicious circle of oxidative stress and mitochondrial dysfunction that the research community has pointed to for more than a decade. I can't find one.

Cuadrado did the definitive work on that in 2010. MJFF refused to fund a phase 2 trial because there was no money in it for Pharma. Patient benefit vs patient suffering was not an issue. Cuadrado saw that the road was blocked and decided to go elsewhere.

Nothing has changed in 12 years.

My analysis is that this black hole is still there and nobody wants to go near it.

Why ?

wriga profile image
wriga in reply to wriga

Meanwhile People with Parkinson's keep on signing up to The Broccoli Seed Tea Research Group...

WinnieThePoo profile image
WinnieThePoo in reply to wriga

Ok. My (limited) patent expertise is HiFi at Pink Triangle and Funk Firm. We patented the use of acrylic for a turntable platter, and later a foam sheet for an accessory mat (the material was marker-board sheet). Cut into a circle and put it on a turntable, and that was patented. Note - we didn't patent acrylic

I need a bit of time for a fuller response, and I have a lot on (work, wife in for knee surgery, new fruit-loop of a rescue German Shepherd dog). Pharma has a business model for profits - the same as housebuilders, banks, car manufacturers, food retailers and Apple iphones. little pharma make small margins out of manufacturing generics. Big pharma like to make big money out of discovering something new and exclusive and are prepared to invest millions in research for it. They are not fussy - if they can make money helping pwp, they will fill their boots.

Pharma are only going to invest in research if they think there is a profitable outcome. To repeat the above, that's just normal business. Why do so many on this forum seem to think because their business is health care, they should be not-for-profit research charities?

I am not really up to speed with your academic papers and very limited human trials, but what I had previously seen was not persuasive. To list a few points at random

I think the home-brew tea idea is a large part of it going nowhere. There are 10 million people worldwide with PD. 1 million in the USA. How do you envisage this therapy rolling out if it proves successful? Neurologists for 1 million US pwp counselling them on brocolli tea production? If sulfuraphane can be extracted, stabilised , and put in capsules, you have a much more deliverable , consistent, therapy, and a very easy option for a placebo control. Why the tea fixation?

Not only have your trials not included a placebo control, they have included a tiny handful of participants (I appreciate you are recruiting for a larger participation). And last I saw, results were modest improvements in some non-motor symptoms. "Pick your success". Apart from the possibility of coincidence - I can't see how it fits with a cohesive model of the disease.

To repeat something we discussed - we both had chronic urinary urgency. My sat-nav still has all the public toilets around Burgess Hill programmed in. Yours was cured by sulphuraphane. Mine just got better (or maybe it was red light hat, or something else). When we went to collect "Mad Louis" (Ludo has had a name change) I went 6 hours without a pee, or even giving a thought to one. How can we be sure sulfuraphane was responsible for yours? Can you describe the mechanism for urinary urgency, and how your solution addresses it? Or do we have a theory of PD and inexplicable random responses with no consistent, repeatable results ?

The hall-mark of this disease is lewy bodies on autopsy. If you have a comprehensive model for the evolution and progress of the disease, how does this integrate alpha synuclein aggregation? How can your "solution" fail to improve all disease symptoms - in particular, apparently, not benefit motor symptoms?

Like I mentioned, you produce a high volume of reading matter, and it is a while since I glanced at it, and I may be missing truck loads. I'm a bit busy now. I'll try to find some time

kevowpd profile image
kevowpd in reply to wriga

The coq10 ph3 trial was 600 pwps over 67 centers. How big were you thinking?

There is money around for testing promising non patentables. You just need to convince the right people

There is also pretty significant (current) private investment into a DMT.

Can you clarify which entities you think are making rivers of gold from PD at the moment?

Jack, can you provide a link to the original article ?

jimcaster profile image
jimcaster in reply to wriga

wriga profile image
wriga in reply to jimcaster

Thanks Jim.

That is good news but, Pd patients would rather hear that they are looking for a cure!

The medical world only appear to look for cures for illnesses that kill us. It is far more lucrative for them to treat illnesses that don't kill us. They are human. We would all do that if we were in their shoes.

But Pd causes patiernts and their families to suffer a life which is worse than death. It gets progressively worse and everybody suffers, both physically and financially.

I understand the medical world only looking for cures for illnesses that kill us. They make nothing out of those, but treating an illness for many years is very profitable for the whole medical world.

It only took a few months to find a cure for COVID-19, because it was killing millions of people. Having Pd is worse than dying, especially for the families. Covid happens once and if it kills us, then our families get on with their lives. But with Pd, it affects every member of that family for many years and often leads to severe financiial suffering, as well as the misery that comes with it.

There is a way to reverse Pd symptoms, which the Mayo Clinic proved in their recent studies. For those who do not undersand what High Intensity Aerobic Exercise is and don't know that it produces a natural chemical that repairs the damaged brain cells, which causes us to get better, I say to you all - until a cure is found, if they are actually looking for it, then you can slowly get better by doing fast walking and producing the GDNF that repairs our damaged b ain cells.

It is in your hands. Don't tell yourself you can't walk fast. Everybody who isn't an invalid, can walk. You can therefor learn how to walk as fast as YOU POSSIBLY CAN! It is up to you! Instead of bemoaning your bad health, get on and do something about it.

As many of you will know, I was diagnosed with Pd in 1992 and by 1998 I was free of most of my symptoms and have lived a good life ever since. I still have Pd and it is getting more debillitating as I get older. I am now nearly 88 and still walking.

Great news. Let’s get that medication for the thalamus.

Brain Hack

We used a roving microelectrode to record vagal-evoked potentials in the thalamus of the macaque monkey. In addition to the anticipated activation in the gustatory/visceral thalamic relay nucleus, we found an unexpectedly larger and earlier response focus with multi-unit discharges in the adjacent >>>parafascicular nucleus.<<<< These data reveal a potent vagal input to this intralaminar nucleus, which is normally considered to be involved in motor control.

Vagal nerve stimulation can be done with a simple TENS unit.

You may also like...