..it was also demonstrated, in a primary neuronal-astroglial co-culture system, that the overexpression of α-syn significantly decreased the levels of glia-derived neurotrophic factor (GDNF) and partly inhibited neurite outgrowth. Although direct evidence is currently lacking, it was proposed that dysfunction of the ER-Golgi compartment in astrocytes overexpressing α-syn may lead to a decline of GDNF levels, which in turn would suppress neurite outgrowth.
From:
α-synuclein induces apoptosis of astrocytes by causing dysfunction of the endoplasmic reticulum-Golgi compartment : GDNF : 2018.
Woof. Is there a simple version? I kinda thought I got the gist, and that bodes well for the drug I am trialling.
I also, kinda thought I got the (very complicated) conclusion that A-syn blocks, inhibits, or results in reduced levels of GDNF.
This fits with the Bristol research teams Mir-7 results (although the 2 appear not to have heard of each other or their work), and again , if I have not got the wrong end of the stick, is going to be a good thing for BIIB054.
The case for placebo is absolutely no adverse effects whatsoever (apart from feeling like a pin cushion - 8 blood samples plus the infusion each visit. And the full body wax - I am quite hairy - ECG's and infusion catheter adhesives cause a few bikini wax moments)
I get phoned the day after an infusion, and a week after, by my supervising doctor, and she just gets "nothing, completely normal" in response to her enquiries.
I'm well aware how easy it is to imagine things, and how variable and subjective some things are, and how the original theory was this drug slows progress, and isnt expected to show symptomatic relief - the measure of success will be slowed progression at the end of 2 years.
But...
Today is my birthday and the one year and two days anniversary of my diagnosis, and my wife commented "I don't think its progressed at all - I think you are improved". Pooing (my specialist subject) is fully normal , and I am sure my sense of smell is improving (although not normal). Both of those were much improved on last year following the microbiome diet, but seemed more so (progressively in the case of smell) since starting the trial.
A really bizarre apparent effect , which seems to fade over the 4 weeks, is the eyelids round my right eye. I injured my eye playing badminton as a kid and have had more than 6 major operations which have stretched the surrounding eyelids, and caused them to be puffy and the eye closed. My wife commented how completely open my right eye is now - and she's right. Just not sure it started with, or is anything to do with the trial.
Oh OK, even if I am imagining it, pain is reduced, I dismantled 2 sheds with a builder mate with no tremor (hard graft, and a lot of wobble inducing use of a cordless drill to remove hundreds of screws), I am completely still at night, and seem steadier more of the time. Tremor still fluctuates, but seems less often, and less severe , and I could nearly have forgotten I have PD for the last few days.
There - bet that's jinxed it and it all goes tits up now
The researchers seem to have identified participation of endoplasmic reticulum and astrocytes but are so busy reporting what they haven't found that their findings becomes lost in their verbiage.
Just wondering if you can translate this into simple English for people who have not studied science at a tertiary level. Not a knocker so please don't take offence.
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