Parkinson's: Understanding its more than a movement disorder may speed a cure

[p-oui]

It is increasingly evident that Parkinson disease (PD) is not a single entity. PD is a heterogeneous disorder, meaning no two individuals have the same symptoms, disease course or treatment response. Defining subtypes of PD further helps understand underlying mechanisms, predict disease course, and help design personalized management strategies.

For example, 4 core Parkinson's disease subtypes:

(1) younger disease-onset,

(2) tremor dominant,

(3) non-tremor dominant, and

(4) rapid disease progression.

The common denominator? Alpha-synuclein protein clumps (Lewy bodies) appear to be as they are seen in the brains of nearly everyone with Parkinson's. This provides new insight and could change how Parkinson's is treated.

consultqd.clevelandclinic.o...

[CPT_Helen Partner]

This is a hugely important topic for discussion. It would be amazing if we could find a way to explore this even further, making sure that non-movement symptoms are included too - but that PwP help define the condition. How can we do this? Advice would be much appreciated.

Helen

[Hikoi]

"It may be best to view Parkinson’s as multiple diseases with different underlying causes and manifestations,” he concluded. “If we focus on developing specific treatments for each of these ‘PD variants’ rather than trying to find the silver bullet that will eradicate all of them at once, we may have more success.”

Good article p-oui, thankyou for it. Using the 4 categories you have outlined i wonder if there are papers on the differing symptoms and treatment approaches for each type. Using those types for exploring peoples experiences of pd might be a place to begin. Im not sure if that is in line with what CPT-Helen is looking for.

[Serenity_finaly-1 in reply to Hikoi]

YES YES YES. This is what I have been trying to say for a long time now. Parkinson's is more of a communication disorder. Communication with the brain and the body, the brain and the brain ( those things that should be automatic ), and the brain communicating with other brains.

[Opt8 in reply to Serenity_finaly-1]

Yes! I've been told it is also like muscle illness that the brain controls

[Serenity_finaly-1 in reply to Opt8]

I asked my Doctor if they looked at it as a mental illness because they both have a chemical deficiency as the base. Her response was that she considered it a neuro illness.

[Motal in reply to Hikoi]

Hikoi, agreed. It's beyond frustrating to think of trials that throw one subgroup's baby out with the this-doesn't-work-for-the-entire-group's bathwater.

Do we have any idea how often this happens?

Is there some governing body that could set the standard so the trial results were broken down by subgroup?

Is that something CPT and MJFF could back?

[Hikoi in reply to Motal]

Motai

I think these categories are just our beginnings. Dumplekin gives the source of the research paper and its dated 2006.

These categories use stand out features, observable data. I dont think that they have been developed or become universally used.

There is no world governing body setting standards for trials. I think organisations like CPT are in the fore front of change and they would back initiatves, to advance this, see CPT- Helen's post above.

So what can we do to build up a bigger picture of subtypes? How can pwp progress this? To begin by getting pwp to give their ideas and experience of symptoms and so develop the knowledge of categories? When the caegories are generally accepted, probably through the Movememt disorder Society, then we can lobby for their use.

Also it would be helpful to have guidelines / criteria we can use when reading reports on therapies for pwp to see if the therapy would be likely to work on us.

BUT first we need the agreed categories!

[aspergerian in reply to Hikoi]

Perhaps someone could post the name of the UK presenter who gave such a powerful presentation in video Hikoi posted recently.

[Motal in reply to Hikoi]

Hikoi -

Thanks for laying that out.

Am still a bit hazy about "a bigger picture of subtypes." Would it mean, for example, specifying affected sides of the body -- left side tremor or right side tremor and left side rigidity and right side rigidity? Similar distinctions within the subgroup of Young Onset?

I recognize further distinctions beyond L, R, Tremor, Non-Tremor, YO might be useful - though I'm unclear what they might be. Particular non-motor symptoms? Any suggestions?

With the clock ticking and no reporting requirements by subgroup now in place, that line about "Perfection being the enemy of good enough" comes to mind. How granular do those standards need to be?

Helen, can you provide any guidance on this?

Cheers, Motal

[Hikoi in reply to Motal]

My guess is this

perspectivesinmedicine.cshl...

nature.com/nrneurol/journal...

[grower]

That was really interesting, thanks for posting

[johntPM]

As I see it, one of the reasons why so little progress has been made is that trial design has been poor: we think that we get more accurate clinical trial results by having larger groups. In the world of sub-groups the opposite is often the case.

To illustrate this, let's look at a trial (OK I know the numbers are ridiculously low, but they illustrate the point) with two people, A and B. The treatment benefits A by 10%, whereas B loses 10%.

Old way of interpreting the results: we take the average of the results of A and B, which is 0%, and declare the treatment a failure for everyone.

New way: we asses each individual separately, the treatment is a success for A, but a failure for B.

Treat the individual, not the group.

John

[Motal in reply to johntPM]

I'd be happy if the trials spelled out how each subgroup fared...

[p-oui in reply to johntPM]

John, as I read your comment it seems to be a great missed opportunity to run a trial without considering subtypes. I also agree with the person who said "Perfection being the enemy of good enough", it doesn't look that difficult to categorize yourself. For example, younger disease-onset, is defined as anyone diagnosed before age 50 (as I recall), tremor dominant implies that tremor is your main symptom, etc.,

[Marcomando]

Agreed - I'd be interested to know which group I'm regarded as being in, and how the prognosis for that group differs from the others. Hopefully not the rapid progression group!

However the treatment of subgroups is generally about mitigation of symptoms. Which is helpful, of course, but what we really need is that big breakthrough in attacking the underlying cause which would benefit all sufferers regardless of their variety of symptoms.

I'm hopeful that busting the Alpha-Synuclein clumps is the key. The latest research I've seen suggests there may be a prion (think CJD/mad cow disease) that is the root cause of the mis-folding and subsequent clumping of the proteins.

I understand that trials are on the way for a vaccine to prevent ASN clumping.... Fingers crossed.

[p-oui in reply to Marcomando]

Marcomando, trials are starting the US and I see they are launching in parts of Europe. It feels like we are on the cusp of a break through. I just wish we could speed the process.

[lempa_nik]

"Source of the 4 Subtypes of PD"

p-oui, It may be enlightening for folks to know where the discovery of those 4 subtypes of PD (young onset, tremor dominant, non-tremor dominant, rapid progression) came from. Someone didn't just pull it out of his left ear after having one beer too many, but these researchers used a statistical method of "cluster analysis" (of symptoms) to let the data speak for itself. Here's the source paper:

ncbi.nlm.nih.gov/pmc/articl...

[p-oui]

That is a very good link dumpelkin, here are 2 others:

journals.plos.org/plosone/a...

medscape.com/viewarticle/77... and this is 2017

mdscongress2017.org/Congres...

the pdf cites different studies and states "'The mean age at onset in PD is nearly 70 which is both about ten years older than usually stated and about 10 years older than the mean age at onset in research participants. Many published studies have therefore used unrepresentative patient groups. This selection bias may have an important impact on the accuracy research findings as well as generalisability and further research should assess its influence." and another referenced study cites: Old-age onset PD were, on average, 80 years old at the time of PD onset while middle age onset were 59.

[Hikoi in reply to p-oui]

This may be of interest p-oui

sciencedaily.com/releases/2...

[p-oui in reply to Hikoi]

Thank you Hikoi, PD definitely requires a precision approach, or a highly individualized approach.

[Serenity_finaly-1]

We just keep fighting :

youtu.be/trDsXlDJIbM(Not working as expected?)

[M1tz1]

I got my husband through Alzheimer's using protocols developed by Dr Dale Bredesen, Dr David Perlmutter and Dr Mary Metcalf. My husband's cognitive function was restored. Sadly, he also had PD, as some of you know. The reason why I'm telling you this, here, is that Dr Bredesen and his team found that there are more than 36 possible causes for Alzh Disease. My husband had some of these and correcting them brought him back. At its conclusion, the current article submitted by p-oui makes a similar supposition for Parkinson's. I find this promising, especially if PwP consider all possible developments on an ongoing basis and act on those that seem feasible--while continuing with their PD meds, of course.