Why progress is so slow in finding a solution to Parkinson's Disease

[FMundo]

Why is our research effort for PD so SLOW? Are we barking up the wrong tree? I found this broadcast most interesting

What are the most promising potential treatments for Parkinson's? Professor Peter Jenner at Kings College London gives a unique overview of the science which offers the potential for a cure or better treatments . . .

youtu.be/CuXF-ABDFXo(Not working as expected?)

His thoughts about the problem:

Needed is focus on discrete patient groups when doing research. Right now

we're too focused on "one disease", "one cause", "one cure"

He Suggests repurposing of drugs . . . shorter time, less risk, less cost, side effects known, rapidly explored hypothesis

Anti-diabetics: glitazones, exenatide

Cholesterol lowering drugs: simvastin

Anti-hypertensives: isradipine

Anti-cancer drugs: nilotinib

Anti-malarials: chloroquine, amodiaguine

Iron chelators: desferrioxamine

He suggests - Parkinsons is a syndrome

Differing patterns of pathology and biochemical change

Different subtypes

No single cause or pathogenic mechanism

Classical clinical trials design ignores subtypes

unlikely to find that 'one size' drug fits all

Gene therapy and stem cell approach

Neuroprotection seems a more difficult and longer term objective

Modification of processes linked to gene defects may provide modifying

treatments

Treatment must be started early

All these approaches must be aimed at the complex pathology of Parkinsons

What are your thoughts. Is he on track ?

[Maja54]

Hi FMundo.The reason for scientists are not finding cure for PD because pharmaceutical companies do not imyciaye any it is more profitable for them to have us sick then heaving us healthy .Healty people do not spend money on dugs. It has been 50 years sense Snamet vas discovered nothing sense .Just think ,so much money is donated so many brith people on the job and nothing. I know this sounds very conical but that is the way I feel.I have the pleasure inducing this disease for 16 years ,At first I vas so hopeful l I pray and prey. Even afrer mY DBS , I indur the procedure hoping there be something. Now I come to this conclusion and stop hoping for miracle .

[FMundo in reply to Maja54]

Don't give up hope.... yet. I am involved in the a Clinical Trial (participant - with "skin in the action" - literally). My belief is that with a deeper more committed approach (like was done for HIV) , recognition of PD as a syndrome and not a particular disease. . . adoption of running clinical tests that are more sophisticated in grouping participants based on genetic &etiological factors with the perspective that we're not dealing with a single disease so that effective therapies for particular types of Parkinsons can be detected. When I consider that the Trial that I'm involved in (and which is costing $100,000 for each participant, which is typical) collects little information on me (other than the fact that I'm 72, male, diagnosed four years ago, Stage 2.5) . . . I have to shake my head in wonder.

If we're going to get serious about finding a solution to PD, we need to refocus our efforts, stop looking for "silver bullet cure". Yeh, it might not fit the model of drug companies and their stockholders who are seeking the magic pill that they can charge $500K for. Maybe the solution to PD is a custom designed cocktail of drugs that control the disease similar to how HIV is controlled. That one therapy does not fit all. The customized approach - as we see going with oncology.

[jeffreyn in reply to Maja54]

Hi Maja54,

For another point of view, you might like to consider this recent interview with a former pharmaceutical executive, who is now a patient advocate and PwP.

tmrwedition.com/2018/05/15/...

[FMundo in reply to jeffreyn]

Thanks Jeff for this article. I read it with interest. I do not subscribe to the idea that pharmaceutical companies are not interested in treating sick people ongoing rather than curing them. I do believe that many, if not most people who work in research and even in marketing for drug companies do that with a motivation to do good things and care for people. And I can kinda look the other way as the industry pocketed 18 billion dollars of tax refunds by buying back their stock and giving fat bonuses to management rather than lowering exorbitant drug prices. Washington - those idiots in the Trump administration asked nothing of corporate America in general for the tax relief. What I do object to is the fact citizens of the U.S. pay three or four times MORE for drugs than citizens of foreign countries. We underwrite drug development and do a fair share of being guinea pigs in Clinical Trials (excepting the really dangerous human testing which we have done on people in desperately poor countries). However rich western countries "negotiate" with drug companies. Lobbyists make sure prices stay real high in the U.S. Its time to level the playing field and have everyone pay their fair share of costs. Nilotinib (the drug trial I'm in) costs $120,000 a year in the U.S. In Canada its less than $20,000

[MBAnderson in reply to FMundo]

Frank & Jeff,

I agree with you, Frank, that many of the people who work in drug companies are well-intentioned and care for people not unlike many of the engineers who work in the automotive industry actually want to make their cars safer, but 1) those people aren't making the big decisions, and, 2) the purpose of an automotive company is not to get us from point A to point B, the purpose of a corporation, for which they are legally obliged, is to make money. They've just chosen to make money by making cars like the drug companies have chosen to make money by making drugs.

So for that reason, I don't have anger toward the drug companies for not finding cures for diseases, because that's not why they exist. (I do have anger though, but for other reasons, such as in their quest for profits, top-level executives are perfectly happy to withhold and distort data knowing they will be killing people.)

I'm also ambivalent about their pricing of drugs because as long as we embrace unfettered free enterprise, a company is entitled to charge what the market will bear. The fault lies with the government's declination to negotiate drug prices as do the governments of all other advanced democracies. Notice that the VA pays a fraction of what individuals and insurance companies pay for the same drugs because at the VA, the cost is being borne by the taxpayer and politicians don't like to spend money on things like drugs -- because the cost of drugs is not a problem for politicians. (I know with certainty they use to afford themselves single-payer and if they don't still, you can be sure they're not paying for their own healthcare.)

There are often smaller cohorts within these drug trials that benefit significantly from the drug being tested, but by themselves they are too small a market.

Capitalism will not ever find a "cure" for Parkinson's (because there is no such thing and) for the reasons Mr. Jones explained, so were stuck with re-purposing which, likewise, will not find a "cure," but will find therapies in varying degrees of success for various subsets. Unless or until private funding comes up with several billion dollars to build on basic research, there will always be some PWP who find little, if any relief.

The only relief for people with chronic illness is government and private funding and a public option or single-payer -- the way the rest of the developed world does.

That f*ck head Mitch McConnell keeps saying, "Well, we don't want to be like them, like Scandinavia, like Europe." Actually Mitch, we do, we want to be exactly like them.

Jeff posted a good article on re-purposing a couple weeks ago.

link.springer.com/epdf/10.1...

[wriga in reply to MBAnderson]

Hi Marc,

HU brought up this thread on response to a post I made. Maybe you saw it. The politics is the same.

patientresearcher.com/2020/...

[PixelPaul]

I found this very interesting, thank you for posting.

[Farooqji]

reason is lack government interest

[M1tz1]

Excellent. He sounds like US neurologist, Dr Dale Bredesen, who is bringing many people back from Alzheimer's (AD) not with one drug but with a holistic and individual approach. He says there are 36 possible causes of Alzheimer's that are not necessarily the same in each patient. It's like having 36 holes in a roof. Close one (using a single drug) and the rain still comes in. Close many and we're getting somewhere. He asks why each patient has PD and after many tests, treats each as a unique case. Following this protocol, I gratefully got my husband's cognitive function back here in South Africa. I've also wondered whether PD could be approached in the same way. Sounds so promising--and (to me) convincing. Wish it were not too late for my husband. Thank you FMundo.

[JennyBies]

Research is conducted by different types of labs:

1. Pharmaceutical companies have to make a profit to enable them to keep doing what they do. They also have the best resources for clinical trials.

2. The National Institutes of Health (NIH) are federally funded by taxpayers' dollars. They have extensive research facilities and provide grants to other outside research labs especially in academia.

3. Academia/Universities and colleges teach and train scientists at all levels. They are typically responsible for the research that identifies individual genes and molecules, characterized pathways and mechanisms. They receive some funds from the schools. But most of the funding comes from outside sources like the NIH or the Michael J Fox group.

4. There are nonprofit groups like St Jude and Mayo who receive donations and apply for NIH grants.

5. And there are Biotech companies who are for profit and research topics with promise in the near future. If they find something they often collaborate with pharmaceutical companies to get it into clinical trials.

Individual scientists don't become scientists for the money. It's not a financially lucrative profession especially in comparison to the years of education required. And the lab coat fashion is a smidge mundane. These people are motivated by other factors: fascinated by the topic, the challenge, a wish to make the world a better place, and/or someone close to them has/Had a similar disease. They truly WANT to help find the cures. They are frequently very dedicated to and passionate about their work. They go where they are most likely to get the funding to do the research they are interested in. The Michael J Fox group has been helpful in getting funding and resources to these people.

[FMundo in reply to JennyBies]

Perhaps also scientists are motivated by fame and the chance to lead in the competition to find a solution. I understand from NP's that there is a lot of ego involved.

[JennyBies]

On a side note, I was a molecular biologist before I retired on disability thanks to the Parkinson's. I never worked in the area of Neurology. When I was in graduate school working on a Master's in Microbiology I was very interested in prions. (Prions are infectious proteins that form plaques similar to the plaques found in other neurological disorders.) However I was advised to avoid Neurology because many students were not successful and had to either switch projects or give up on their graduate school degree. Their research assistanship would be at risk of running out before completing the study. The students who were successful required much more time to complete their research. At that time (circa early 1990s), there weren't very many cell culture models for Neurology. The research tools that were available were either very challenging or just weren't in place or easily accessible to ensure success in Neurology and prions. Michael J Fox group has probably been very helpful in ensuring the scientists in training and dedicated to their work in Neurology had the funds to complete their work.

I had a peak at an article discussing the cellular models that are currently in use. Link below. (Please note that reading 1 article should NOT imply experience with or expertise on my behalf with these particular cellular models.) The cells in use were not the traditional, easy to use cell lines. The article mentioned using primary cells. Generally primary cells are more delicate than their counterpart immortalized cells. And neurons have traditionally been slow to grow in tissue culture as well as in nature. In addiction these cell culture models appear to have been developed after 2000.

ncbi.nlm.nih.gov/m/pubmed/2...

The progression of any research and (hopefully) a subsequent cure is very dependent on the tools available and their ease of use. These considerations typically have a greater impact on the progression and success of the work in a field than the egos of of a few researchers.

[WinnieThePoo]

I think your post, and many of the comments interesting and pertinent. I think Pharma bashing per se achieves nothing. But it is true that their participation is limited to an interest in marketable solutions (the yellow pill). So there is a need for broader research - and some supply of it.

There is a need for a synergistic holistic approach to PD research which is alien to a culture based on segregation, categorisation and specialisation. Hence my frustration elsewhere with the lack of PD neurologist prepared to step outside the brain and look at the gut.

And as I noted on that post - its not like repurposing is that quick (Initiatives like the FDA fast track may improve the situation). Exanatide is a repurposed drug - its phase 1 trial completed in 2013 (five ****ing years ago) and it has yet to start a phase 3 trial which means formal licencing for PD patients is probably going to be 2025. So not as fast as Professor Jenner implies.

But broadly - he is right. I just wish he or someone else would focus a bit of serious research effort on the microbiome, since it has the potential for really rapid delivery. My sort of timescale rapid. Not 12 years like Exanatide.

[FMundo]

I think a healthy contempt for the Pharma industry should be encouraged. The broader the better. Pricing of drugs in this country, often 3-4 times more than it is in foreign countries is a national scandal. What do you think of the Epipen 500% price increase? When asked by a Congressional investigation committee for the justification for the increase the CEO of the company stated "We do so because we can" (and then smirked). The industry makes for a good case study of how an industry can buy what they want with our government. Just for chuckles, why don't you explain to me why Medicare, by law, is not allowed to negotiate drug prices. Interesting law. I wonder who sponsored that one.? Certainly doesn't benefit Joe Q. Taxpayer. Thanks but I'll bash the industry at every opportunity. From the Pharmaceutical industry perspective their 186 million for lobbying is money well spent.

[Maja54]

Hi. evrione next month I am going for surgery to insert tube in my small intestine to start Dodopa drip.

drip.I am at the end stage of the disease.That is my last resort. There is nothing else. After that stop working , I am done. I sees to exist.So talk to me about the resurg and the new things they doing . I am very interested.