Researchers link vascular defects to progression of Parkinson's disease. nilotinib may help

[TL500]

Has anyone seen this?And what do you think?

tangoherbs.com/2021/11/17/r...

[MBAnderson]

It's an article and they should never be taken literally. A nutrition magazine writing about an exotic cancer drug (for Chronic Myeloid Leukemia.) Nilotinib didn't halt the decline. ("...the drug nilotinib was able to halt motor and non-motor (cognition and quality of life) decline..." There has been a lot written about it - the upshot of which it is highly unlikely it will ever make it to prime time.

[TL500 in reply to MBAnderson]

Thanks

[Bolt_Upright]

That article is odd. It seems to run counter to trial results.

Nilotinib in Parkinson's disease: A systematic review and meta-analysis 2022 frontiersin.org/articles/10...

"Conclusions: Although our study demonstrated favorable tolerability and safety of different doses of nilotinib, and improvement in part of CSF biomarker levels of 300 mg nilotinib, the poor efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic."

[kaypeeoh in reply to Bolt_Upright]

My understanding is Nilotinib can stop BBB leakage. For MS my MRI showed leakage at the ventricles, that is, leakage at the BBB. I wondered if that was my case. I don't have signs of PD although the DAT scan shows loss of alpha synuclein through the BBB.

[Bolt_Upright in reply to kaypeeoh]

I agree the BBB repair should be a target. I was just reviewing my protocols for what can help fix the BBB. I did not deep dive on them, but first glance shows most of my supplements should help the BBB:

1: Berberine: researchgate.net/publicatio...

2: Broccoli Sprouts: ncbi.nlm.nih.gov/pmc/articl...

3: If you can fix your microbiome you might be able to fix your BBB: tandfonline.com/doi/pdf/10....

4: Licorice: cabdirect.org/globalhealth/...

5: Lithium: ncbi.nlm.nih.gov/pmc/articl...

6: Magnolol: researchgate.net/publicatio...

7: Niacin: sciencedirect.com/science/a...

8: Nigella Sativa: brieflands.com/articles/jjn...

9: Palmitoylethanolamide: sciencedirect.com/science/a...

[Little_apple in reply to Bolt_Upright]

This excellent list deserves its own post

[Bolt_Upright in reply to Little_apple]

Thanks, I will do that.

[Bear1927 in reply to Bolt_Upright]

what kind of Lithium supplement would you recommend?

[Bolt_Upright in reply to Bear1927]

There is a lot of info in this thread: healthunlocked.com/cure-par...

I use Lithium Orotate myself, but that does not mean it is the best. Please read that other thread.

[Victor1975 in reply to Bolt_Upright]

Interesting same 7study tell that 300 mg Nilotinib help ng.neurology.org/content/7/...

[Bolt_Upright in reply to Victor1975]

Thanks for the link. Results seem a little mixed.

"This study primarily demonstrates alteration of CSF miRNAs, which regulate collagen, ECMs, and angiogenesis—as well as autophagy-lysosome pathways—over 12 months in patients with moderately severe PD, suggesting impairment of these pathways in disease progression of these patients. Previous cross-sectional studies suggest that CSF biomarkers of angiogenesis34 or autophagy4 are increased in PD. No longitudinal analysis was performed to demonstrate vascular impairment in Parkinson disease, thus this report represents novel findings that vascular defects may be present in the disease. We previously showed some changes in UPDRS over 12 months,15 but these changes were not statistically significant because of optimization of PD therapies in the placebo vs the nilotinib (150 mg and 300 mg) groups. Indeed, the present data show that UPDRS II + III worsened 2.39 points over 12 months in the placebo group, whereas nilotinib, 150 mg and 300 mg, did not change. In addition, statistical significance between groups was not seen after 12 months of treatment primarily because the phase 2 study was statistically underpowered (by design) for clinical outcomes.15 However, long-term treatment with nilotinib 300 vs 150 mg over 27 months showed significant clinical differences between the groups.21 When placebo was switched to nilotinib, 150 or 300 mg, for the second year, UPDRS II + III worsened 7.8 points in 150 mg, whereas it improved −5.7 points in nilotinib, 300 mg. The observed longitudinal changes of miRNAs and the correlation between miRNA changes and clinical outcomes suggest a disease-modifying effect of nilotinib, 300 mg."

[TL500 in reply to Bolt_Upright]

Thanks

[Victor1975]

ng.neurology.org/content/7/...

[Boscoejean]

some of the potential side effects seem a little concerning

[MBAnderson in reply to Boscoejean]

I consider it a dangerous drug. PWP participants are carefully screened (for long QT syndrome) so the results don't apply to everyone with PD. Also, they cannot ingest anything, food, supplements, other drugs, that are metabolized by CYP3A4 (which is a lot of stuff.) M.J. Fox Foundation halted a trial.

[TL500 in reply to MBAnderson]

So it's not like what it says in the article.

[MBAnderson in reply to TL500]

right

[TL500 in reply to MBAnderson]

☹️