adssx
#382
Interesting! A trial of azathioprine (common alternative to methotrexate) has just ended in Parkinson’s disease. Results will be published soon…
3 Likes
adssx
#383
There’s only one old small Brazilian trial of riboflavin in PD: High doses of riboflavin and the elimination of dietary red meat promote the recovery of some motor functions in Parkinson’s disease patients 2003
19 patients, no placebo:
riboflavin orally (30 mg every 8 h) plus their usual symptomatic medications and all red meat was eliminated from their diet
All 19 patients who completed 6 months of treatment showed improved motor capacity during the first three months and most reached a plateau while 5/19 continued to improve in the 3- to 6-month interval. Their average motor capacity increased from 44 to 71% after 6 months, increasing significantly every month compared with their own pretreatment status (P < 0.001, Wilcoxon signed rank test). Discontinuation of riboflavin for several days did not impair motor capacity and yellowish urine was the only side effect observed.
There’s also this ongoing trial: Validation of a Novel Functional Food Designed to Meet the Nutritional Needs of People Living with Parkinson’s Disease (Food4PD). Twice daily: “An enriched functional drink containing chicory inulin (10g), folic acid (100µg), vitamin B12 (5µg), vitamin B6 (5mg), riboflavin (2.5mg) and vitamin D (5µg).”
On the other hand: Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson’s disease: a case–control study in Japan 2010
After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0·87, 0·70 and 0·11, respectively).
2 Likes
Rapan
#384
At least one epidemiology study suggests that MTX (methotrexate) doesn’t increase risk for Parkinson (for RA patients although RA is correlated with higher risk for Parkinson).
Interestingly, chloroquine and hydroxychloroquine reduced risk by about 25% for Parkinson.
https://www.neurology.org/doi/10.1212/WNL.0000000000013303
2 Likes
Satchel
#385
Perhaps it’s been brought up, but Klotho is mediated through Platelet Factor 4 in the brain and Dana Dubol has shown that PF4 is almost completely protective in PD neurons (not motor neurons). Unlike Klotho, PF4 is readily available for human use for 20+yrs.(used in a surgery setting). Human doses are already published; safety is excellent and I think Dubol was using 1 sq inj every 2-3 wks. I will dig up the paper, but if I had PD I would certainly consider PF4. Lots of different suppliers
3 Likes
adssx
#386
Do you have a link to the source?
A quick search on Google Scholar points to… zero evidence in favor of PF4 for PD. Do you have some sources?
1 Like
Satchel
#387
You have to read a couple of papers to put it together, -which I will list. In a nutshell Klotho via PF4 abrogates alpha-synuclein affects on cognition to 70% of normal. - but does not help motor difficulties (which they have established treatments for). I have to search again but i had found a clinical trial a few months ago- I will hunt it down as well. Basically why bother with Klotho when an established treatment is already approved now-all be it for a different disease process.
https://www.nature.com/articles/s43587-023-00468-0
Quote from Dena Dubal talk with Peter Attia -“PF4 to mice as a shot in the belly (just like they had given klotho), and found it enhanced cognition in young mice, and in an aging mouse it reversed cognitive defects ‒ it was totally remarkable”
1 Like
Satchel
#388
The top link doesn’t seem to connect so here is the title
Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice
adssx
#389
That’s the first paper in mice?) We don’t even know if alpha α-synuclein causes PD, same issue with beta amyloid in AD…)
What does this mean? There’s no disease-modifying treatment for motor symptoms in PD. There’s only levodopa that reduces the tremors but after 5 years it gives you dyskinesia that is even worse.
It does seem aberrant splicing is part of PD.
I started playing around with coversations with 01 about splicing, cancer, PD etc.
I do this in the dark because it enables my superchiasmatic nucleus to think it is the end of the day (which it is) whilst still processing information.
What I really need to do is to put together something from o1 where I have checked the references and tracked things down to avoid hallucinations that looks at aging, cancer, diabetes, PD and aberrant splicing.
What seems to be the case is that acetyl-CoA shortage causes both splicing changes and otherwise long genes not to be transcribed.
This is quite rational, but appears to drive the phenotypes of aging which includes PD. It would be good to do some biohacking trials with younger PD sufferers to see if this* can fix it.
*this being increasing cytosolic acetyl-CoA through a range of biohacking techniques.
1 Like
adssx
#391
And klotho and/or PF4 would fix that @John_Hemming? (I don’t know enough about klotho…)
adssx
#392
We have @TomParkinson here who is doing a lot of biohacking on himself.
Dr. Laurie Mischley is doing biohacking with her PD patients. See for instance: Parkinson Symptom Severity and Use of Nutraceuticals
And you might find people willing to try on Reddit or on HealthUnlocked.
1 Like
I am wondering if CureParkinsons would be up for this.
1 Like
adssx
#394
@Pender: Interview from #CTAD24, Charbel Moussa of Georgetown presents the findings of the Phase II trial of nilotinib in patients with dementia with Lewy bodies: A Phase II trial of nilotinib in patients with dementia with Lewy bodies | VJDementia
tl;dr:
- Stabilization of the motor symptoms in PD
- Nilotinib increases dopamine levels in the brain
- No adverse effects (the placebo group actually had more adverse effects)
- In AD, at 300 mg, some mood swings. Not at 200 mg.
- In Lewy body dementia, with the current drugs, when you treat motor symptoms, you increase the non-motor symptoms and vice versa.
- Improved biomarkers (Aβ and tau phosphorylation)
- As early as 3 months, improvement in ADAS-Cog14 (cognitive scale) that continued to 6 months
- No motor improvements but 70% reduction in falls
- It’s hard to measure but it seems that motor fluctuation reduced
- His conclusion: Nilotinib 200 mg is safe, doesn’t worsen motor symptoms, lowers the number of falls, improves cognition and probably motor fluctuations
- Next step: larger multi-site phase 3 trial in Parkinson’s disease dementia and Lewy body dementia
2 Likes
adssx
#395
TKI look interesting indeed: Use of Receptor and Non-receptor Tyrosine Kinase Inhibitors Is Associated with Lower Risk of Developing Parkinson Disease 2024
All 11 TK inhibitors were inversely-associated with PD. Beneficiaries taking tyrosine kinase inhibitors targeting ERBb (Erlotinib, RR 0.51, CI 0.35–0.74), TEC (Ibrutinib, RR 0.60, CI 0.49–0.74), or PDGF, VEGF, FGFR, and/or SRC, i.e. Sorafenib (RR 0.48, CI 0.27–0.84), Imatinib (RR 0.59, CI 0.46–0.75), Pazopanib (RR 0.58, CI 0.39–0.88), Nintedanib (RR 0.67, CI 0.50–0.90), Sunitinib (RR 0.64, CI 0.41–1.00), and Dasatinib (RR 0.54, CI 0.35–0.83) tended to have the most marked inverse associations. The nrTKIs inhibiting JAK, i.e., Ruxolitinib (RR 0.81, CI 0.60–1.10) and Tofacitinib (RR 0.88, CI 0.68–1.14), exhibited more modest inverse associations, as did the ABL/PDGF inhibitor Nilotinib (RR 0.71, CI 0.47–1.09).
@DrFraser: might be worth an article on your blog 
(I still think there’s not enough data, but we’ll soon have the results of risvodetinib in PD and baricitinib and dasatinib in AD: Parkinson's disease - #341 by adssx )
1 Like
adssx
#396
Another positive phase 2 trial in DLB: Cognition Therapeutics Announces Positive Results in Phase 2 Study of CT1812 in Dementia with Lewy Bodies
Importantly, there was an 82% slowing in the total neuropsychiatric inventory (NPI) with particularly strong reduction in anxiety, hallucinations, and delusions in the CT1812 treated arms. In addition, there was a marked reduction in caregiver distress, which suggests a positive impact on the day-to-day lives of those receiving the drug. Participants treated with CT1812 experienced a slowing of decline across all three cognitive measures compared to placebo, including fluctuations in attention which declined by 91%.
Very impressive. Markets were positively surprised:
CT1812 is an experimental orally delivered small molecule oligomer antagonist that penetrates the blood-brain barrier and binds selectively to the sigma-2 (σ-2) receptor complex, which is involved in the regulation of key cellular processes. These processes are disrupted by toxic interaction with Aβ or α-synuclein oligomers, oxidative stress and other disease drivers. The ensuing damage to sensitive synapses can progress to a loss of synaptic function, which manifests as cognitive impairment and disease progression.
It’s also tested in Alzheimer’s disease and dry age-related macular degeneration.
(poke @Pender)
5 Likes
DrFraser
#397
The one I have the most access to (and have even taken myself) is Dasatinib, which taken short term (e.g. a few days) seems probably safe. But taken long term daily, I have concerns.
Do we know anything about the doses/duration they were looking at. Off shore, Dasatinib is cheap, and most folks are taking with Quercetin/Fisetin.
3 Likes
adssx
#398
Yes I think it’s way too early to tell for now given how risky this drug is: List of adverse effects of nilotinib - Wikipedia
3 Likes
adssx
#399
Laurie Mischley has just published the 10y summary report of her “Modifiable Variables in Parkinsonism (MVP) Study”: 10 YEAR SUMMARY REPORT
5 Likes
cl-user
#400
Interesting stuff in that report. Melatonin seems bad for PD and CoQ10 is good (low dose lithium too) to just look at 2 favorites here.
Obviously exercise but also yoga is goo
The usual good and bad food. BTW only look at those with confidence intervals not crossing 0 so basically discard anything from egg to beef.
4 Likes
The report itselt notes that if you correct for the use of melatonin for insomnia then it is the insomnia that is mainly the issue.
This is the essential problem of studies of this form. The details really matter.
I will stick with my hectodosing (slightly higher now) of melatonin.
1 Like
