[ZucchiniFlower]

We've talked before about PD perhaps being a group of syndromes, with different causes, different pathologies, different symptoms. Researchers need to take that into consideration when they plan their experiments, or drug trials.

Add to that the whole placebo fiasco, I tend to think that only basic research will come up with the answers we need.

Take for example the LRRK2 mutations, only discovered a few years ago. They are the most common mutations, too. My Dad had PD and we are ethnically Ashkenazi Jews, so I probably have the LRRK2 mutation along with my Dad.

There are several LRRK2 mutations, but with our ethnic background it's probably the G2019S mutation.

So, I'm reading an article about LRRK2, and I find something very interesting to me. ....

"In conclusion, our studies suggest that LRRK2 is expressed and localized to a variety of neuronal populations in human brain regions directly implicated in the neuropathology of PD, including the nigrostriatal dopaminergic pathway and especially the dopamine-innervated neurons of the caudate–putamen.

In the caudate–putamen, LRRK2 is primarily localized to cholinergic, calretinin- and GABAB R1-positive interneurons, suggesting that LRRK2 may be associated with extra-pyramidal movement functions of the basal ganglia. In addition, LRRK2 occasionally localizes to brainstem LBs but not cortical LBs or Lewy neurites in PD brains.

It will be of fundamental interest to determine the molecular mechanism(s) by which pathogenic variants of LRRK2 give rise to basal ganglia pathology leading to PD."

Well, lo and behold, the two drugs that I take are right on target. Artane (trihexyphenidyl) is an anti-cholinergic, and baclofen is a GABAB agonist.

Plus, the symptoms troubling me the most are the extra-pyramidal motor problems, with lack of coordination, over activation, spasms, dystonia, bradykinesia. I take as little artane and baclofen as possible, because of side effects.

Plus, in two SPECT scans, I had hypo-perfusion in the left putamen.

So, it's making sense to me now.

I tell you this, because my experience with symptoms and causes is probably different from yours. We're probably all different.

Heck, even my Dad had different symptoms. He had tremor; I don't. My bradykinesia is worse than his was. That's a common occurance in families with LRRK2. LRRK2 is known for pleomorphic pathology. At autopsy, our brains look different, with different areas affected.

How to plan a clinical trial when we're so different and are prone to react to placebo?

Localization of Parkinson’s disease-associated LRRK2 in normal and pathological human brain
2007

http://www.sciencedirect.com/science...b05abc7c606708



LRRK2 G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews
2006

http://content.nejm.org/cgi/content/extract/354/4/424

[BEMM]

Zucchini Flower,
You would help research by taking advantage of the DNA PD project on 23andMe, and find out if you do carry the LRRK2 mutations. You most likely do.
Yes, we are all different. There are no indications in my DNA that would have predicted PD, I even have less than average chance for having PD - but I do, and it started in my early 50s so it is not brought on by an abundance of years.
As an extra treat is has been fascinating to find out that my maternal genes are not Danish at all. Through the maternal line I am related to the Basques, the Berbers and the Finnish Lapps ......... I would never have known that - I thought I was completely generic.

[ZucchiniFlower]

Your genetic surprise is very cool.

Thank you for the nudge! I'll send my spit test this weekend. I always think of Labor Day, as the beginning of a new year. I need to turn over many new leaves. I"m hoping the fall leaves will inspire me. Anyway, I'll stop procrastinating my life away. First up: S P I T

~Zucchini