Parkinsons disease - A complex multisystem disease likely to be multiple diseases

Article from 2017 but very interesting.

"
Much more than a movement disorder
PD is now recognized to affect just about every system in the body, causing dermatologic, urologic, musculoskeletal, gastrointestinal and psychiatric symptoms.

Early signs and symptoms of PD — including hyposmia, impaired color vision, constipation, genitourinary dysfunction, depression, anxiety, restless leg syndrome and REM sleep behavior disorder — reflect the progression of synucleinopathy and can manifest decades before motor symptoms appear.

REM sleep behavior disorder appears to be a marker for a specific subtype of PD with a high prevalence of cognitive disturbance and is a strong risk factor for developing dementia. Insights like these are especially important for identifying people more likely to develop PD for recruitment for clinical trials of preventive therapies."

"
Environmental factors are critical
Only 5 to 10 percent of PD cases can be attributed to genetic mutations. The overwhelming majority are believed to be due to a combination of genetic susceptibility and environmental insult. Head trauma — particularly with loss of consciousness — especially increases risk, as does exposure to the pesticides paraquat and rotenone.

Other factors have been found to reduce risk (smoking, coffee, high uric acid levels, calcium channel antagonists), offering an important focus for research. Isradipine, a calcium channel blocker, and inosine, a uric acid elevator, are currently undergoing large-scale clinical trials as neuroprotective therapies."

"
Biomarkers for diagnosis, progression on the horizon

The lack of a definitive test for PD hampers clinical care and research progress. Efforts are underway in a number of avenues to remedy this. "

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I had no idea that there was no biomarker for PD.

eta: when anyone says 'well there is no test for ME' we can say 'well there isn't for Parkinsons either but no-one questions the validity of PD as a 'genuine disease''.

 

Interesting than inosine (which is part of inosine pranobex or Imunovir) is being studied as a neuroprotective in PD. Maybe it's that that has helped ME patients, rather than (or in addition to) its immune properties.

 

Its true that there is no biomarker. The only way to be sure is an autopsy, even brain MRI/spect does not always show abnormalities. Also it does affect more then Dopamine, which is not commonly known, many patients experience deficiencies in Acetylcholine, Serotonin, Orexin and several other neurochemicals. REM Behaviour Disorder carries something like an 80% chance of Parkinsons developing in the next 10 years and dementia affects about 75% of Parkinsons patients after many years with the disease. Also some patients actually have lewy body dementia and not Parkinsons though the two conditions are considered related.
There are other diseases with no biomarker, narcolepsy (thought to be psychosomatic till 2001) and a few others i know of that i can't extract from my brain right now.
Oh and there is a phase 2(?)drug trial on a chemotherapy drug (Nilotinib) that produces dramatic improvement in Parkinsons by blocking a protein called ABL1 which seems to keep alpha synuclein from forming clumps and killing brain cells but it was only designed for short term use and was never tested on humans for indefinite use (withdrawal from the drug causes symptoms to return in a few months).

As for multiple diseases, i don't buy it

 

Could it be one disease which manifests slightly differently depending on the individuals genetics?

 

Of course, in most diseases everyone presents a bit differently based on genetics, environment and even things like diet, activity and so on.
Also in Parkinsons there are ways to change the disease progression, exercise can slow the progression significantly. Whether thats heavy exercise or continuous low impact exercise. There was an article in the NYT showing heavy exercise could affect progression and there was also evidence somewhere that i don't remember that dancing therapy can help preserve motor control (perhaps by the brain rewiring itself?)

Some of the drugs used for symptoms control are also believed to be disease modifying, Rasagiline for example

 

Ah yes, I remember seeing PW PD dancing, it was quite amazing and it really seemed to help some.

Yes what I was meaning was, is it not a bit daft to assume there are several diseases until they've looked at people's genetics to see if there is a correlation there which can explain the differences?

 

Yes, its been done, iirc some sequences have been found to increase risk, some cases are directly genetically caused and likely some slow or quicken the progression rate.
Research is always continuing since they get a lot more research money then we do and more will probably be learned about its genetics in future.
There is also secondary Parkinsons, usually caused by things such as stroke, brain tumour, concussion, that sort of thing, which responds well to some therapies used on regular Parkinsons, but usually the prognosis is different, some cases never advance because the cause has remained static or the progression can be very sudden or even resolve because the brain damage was caused by a different mechanism or the brain repaired itself or maybe even neuroplasticity