Real Progress in Parkinson’s
blogs.sciencemag.org
blogs.sciencemag.org
> Before we get too excited: it could be an epiphenomenon. For example, misfolded Alpha Synuclein leads to poor gut motility and that causes appendicitis, which leads to appendectomy. All retrospective studies are contaminated by that possibility, which is why treatments can’t be based on them. However, retrospective studies lead to hypotheses that can be tested in trials. Perhaps not doing appendectomies in people without appendicitis because they are “at risk” for PD–thats a bit extreme.
https://www.ncbi.nlm.nih.gov/pubmed/?term=0+RESEARCH+ARTICLE...
Additionally, I would characterize this as one of many things to be excited about in the PD research / clinical world today:
For example - things that would be useful to patients - characterization of GBA mutations and new therapeutic compounds in the pipeline. Same with LRRK2.
For more in the gut-brain line of thinking - the use of GLP agonists medicines - first shown to be protective of islet cells in the pancreas in diabetes, in a human randomized control trial that showed decreased decline in Parkinson's disease vs. placebo controls.
All of these are something other than a "Me too" dopamine drug.
Plus RT-QuiC techniques for an actual blood test for Parkinson's....
I don't have to mention deep brain stimulation (DBS), which has been around for 3-4 decades, but the newer devices and techniques have an effect size in blinded trials that equal or exceed the effect size of previous trials that were open label...
Can drugs be developed that can chemically attack the misfolded proteins without harming other ones?
I'm not sure that would be a good idea as you know which ones you don't want in certain situations but you likely have no idea if the same ones are useful elsewhere.
BTW if by "drug" you mean small molecule monotherapy, I rather doubt it.
https://www.worldlifeexpectancy.com/cause-of-death/parkinson...
I kind of skimmed the article and went to the Wikipedia link they included for the protein in question. I don't really understand Parkinson's pathology and I've never heard of this aspect of it previously.
But I have a genetic disorder that involves a defective protein and I can speak generally to pathology of that sort, though I can't say for certain how well this applies in this specific case. What I skimmed sounds vaguely similar to the pathology I have read up on for my own condition.
In my condition, what happens is you have two of, say, 1600 or so different alleles (or two copies of the same one) that impact the coding of the CFTR. The CFTR is a protein that forms a cell channel that manages traffic of specific molecules into and out of the cell. The manner in which it is defective varies, depending upon the alleles.
CF is a progressive condition. In other words, it gets steadily worse over time.
I have never gotten any kind of logical explanation from the medical literature for this well established fact. I did my own digging. (I actually was trying to understand something else when I tripped across the following info, but I'm sure no one cares.)
It turns out that derangement of cell chemistry in terms of pH balance and/or salt causes protein misfolds. CF promotes both of those chemical derangements. My inference is that as the body gets more chemically deranged, you see more misfolds. As you see more misfolds, you have fewer functional CFTR channels. This creates a positive feedback loop, aka vicious cycle. Thus, "The normal progression of CF" -- ie you get steadily worse over time.
The misfold matters because basically the way it is folded is what turns a protein string into a useful tool for the cell. Think of Legos or something like that. I mean, that's not a good example. There are toys out there that can be strung together and then bent or whatever. I just can't think of the right name of a good brand.
But you have protein bits that get strung together and if they bend the way they are supposed to, you have a useful tool to accomplish important work in the cell. If they don't, you have a pile of junk that the body needs to expend additional resources on to melt down and either recycle or dispose of as trash.
So the odds are good that Parkinson's involves some specific vulnerability different from my condition and it is made worse by chemical derangement within the cells. Drugs (or dietary changes) that corrected the chemical derangement or prevented the chemical derangement would likely be a good thing to look at.
Correct the cell chemistry, you should see fewer misfolds. Fewer misfolds enhances performance, if only by not wasting resources on churning out a pile of junk proteins that can't be used and now need to be disposed of somehow.
The paperwork is far from useless, traceability and documentation are important. Try to learn about the medical device approval process and FDA, and you might come to like the required steps, or at the least, understand it.
Immune response in reaction to what? I'm not sure how closely leaky gut syndrome is associated with pseudoscience by the HN crowd, but seeming connections like this make me wonder if there's credence to it.
Foods we're not biologically adapted to eat, for instance?
Autoimmune diseases like Crohn's and colitis?