Short answer: Of the hundreds, perhaps thousands, of compounds studied in mice over the past 50 years, all with reports hyping the results, not a single one has turned out to be disease modifying.
“PD does not … develop naturally in any animals except humans.”
“The standard models for PD are designed to produce nigrostriatal dopaminergic lesions usually with 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat or, rotenone. Most of these models inhibit mitochondrial function and/or create reactive oxygen species, but none of them completely reproduces the clinical symptoms and pathology of PD seen in humans.”
“Part of the problem with most of the toxin models is their acute nature, which is completely different from the insidious progression of PD observed in patients. Compensatory changes may arise in patients over the course of the disease that would not have an opportunity to occur in the acute animal models.”
“Although both 6-OHDA models reproduce the major behavioral deficits seen in PD, the effect of the 6-OHDA toxin does not mimic the progressive loss seen in PD. … The MPTP mouse models (as with the other toxin models of PD) fail to encompass the wide assortment of motor impairments seen in PD patients. Perhaps the current rodent models of PD would be more predictive of what will translate into human studies if the time course of dopamine neuron degeneration could be mimicked and behavioral tests were designed to assess the more subtle symptoms ... ”
“… Perhaps one of the most relevant examples … with regards to PD research is the distinction between how humans and rodents metabolize MPTP. Rats and mice are relatively resistant to MPTP, whereas humans are quite sensitive to this toxin.
"Conclusions"
"Rodents and nonhuman primates are an important resource for the study of PD, but the limitations of these models must be kept in mind when interpreting results. Rats and mice are widely used for modeling PD, but no toxin or genetic model completely reproduces the pathophysiology seen in humans."
The problem is even worse than that set forth in the quoted text. The vast majority of rodent studies pre-treat or simultaneously treat with the test substance when applying the toxicant. There are any number of ways the test substance can interfere with the toxicant and as a result the Parkinson's toxic cascade does not even get started. So these studies end up not modeling anything like Parkinson's disease at all.
Any researcher serious about using an animal model to test Parkinson's treatment will use something like the A53T mouse which is genetically modified to produce defective human alpha synuclein. The A53T mutation is known to cause young onset Parkinson's in humans. Such was the case for the study that demonstrated cinnamon to be helpful, and which I and others have found to be so: healthunlocked.com/cure-par...
And so was the case of mannitol experiment in mice, which a number of people - including myself - were sensitive to
Shaltiel-Karyo R, Frenkel-Pinter M, Rockenstein E, Patrick C, Levy-Sakin M, Schiller A, Egoz-Matia N, Masliah E, Segal D, Gazit E. A blood-brain barrier (BBB) disrupter is also a potent α-synuclein (α-syn) aggregation inhibitor: a novel dual mechanism of mannitol for the treatment of Parkinson disease (PD). J Biol Chem. 2013 Jun 14;288(24):17579-88. doi: 10.1074/jbc.M112.434787. Epub 2013 May 1. PMID: 23637226; PMCID: PMC3682557.
The researcher gets recognition by the news industry ( mouse research shows possibility smoking protects against PD ) which gets him some research money from one of the PD associations, enough to buy some more mice. Parkys and care givers get excited and post copies of the research and feel better knowing that somebody somewhere is doing something somehow until some big spoil sport like you and me come along and spoil everything with a cold shower of truth.
The research done in neurology is just for sake of improving the doctor's individual credentials on the basis of which they are able to get jobs and promotions. There is only a limited research which is genuine. I have a deep faith-like opinion that the neurologists and the movement disorder specialists don't know about the origin and root cause of the disease. They have only learned about the symptoms and how to titrate levodopa to manage those symptoms. They don't know about the root cause and how to bring the genuine relief to the patients. They don't know about the useful supplements (B1 for example) neither are they aware of the deficiencies caused by the use of disease or the medication (for example B6 deficiency). I think a good AI tool will be better than a neurologist. In such situation patients have better understanding than the doctors. I have a firm belief that unless the governments do not intervene financially and technically in the field of neurological research nothin will be changed for the next 100 years
While I'm at it, there are two other truths I need to unburden myself of.
1. No internet/video doctor or health guru gets everything right, and, 2. There is no supplement, drug, or compound that does not have conflicting data -- so take everything with a grain of salt.
I didn't know they did FMT people to animals, but I assume it would come closer or would actually duplicate PD, especially if PD does indeed start in the gut.
' In a final set of experiments, the researchers obtained fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients. '
I will volunteer to get mouse poop from a lucky PD-free mouse transplanted to my microbiome to see if the reverse is true! Does that study include free cheese?
At least some Parkinson's syndromes have psychological components to them. It seems to me that the method of producing a Parkinson's like pathology in mice is too basic, therefore not reflecting the multifactorial causes in humans. The model is too simple, wasting time and money as well as potentially disregarding treatments that could benefit a subset of PWP.
Do you get the feeling that it's like a thousand researchers in a huge dark room groping around for a door. No one in charge, all bumping into each other. No coordinated effort.
Ugh, you are so right. I think the problem is, researchers are basically NOT ALLOWED to test their drugs on humans unless they can show some effect on animals.
I have not read the research on Loin’s Mane, but regardless of whether rodents were used, the claim that Loin’s main promotes nerve growth should be of interest to PD. So what if no known species other than humans are believed to get PD; so what if chemicals are used to mimic PD; nerve growth is nerve growth and should be beneficial to PD.
The "what" is that the tested compounds are performing in conditions that are not Parkinson's, in beings that are not, i.e., different than humanoids, and therefore irrelevant to pwp.
That nerve growth happens in a mouse does not mean it will happen in a person
"...chemicals are used to mimic PD." That's the point, they don't mimic PD.
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THC/Marijuana: Why/how does it work for PD?
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Why do only humans get PD?
