Addressing the Blood Brain Barrier Permea... - Cure Parkinson's

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Addressing the Blood Brain Barrier Permeability Issue

Bolt_Upright profile image
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TL500 posted an article "Researchers Link Vascular Defects to Progression of Parkinson’s Disease" tangoherbs.com/2021/11/17/r... that talked about the Blood Brain Barrier Permeability issue with PD.

I have long believed that attempting to improve the BBB should a big part of my protocols. 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...

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Discogs_discogs profile image
Discogs_discogs

The article which you posted seems to be saying that the answer is the repurposed drug NILOTINIB. Has there been any other research stating this drug halts PD or fixes the blood brain barrier?

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Discogs_discogs in reply to Discogs_discogs

frontiersin.org/articles/10...

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Discogs_discogs in reply to Discogs_discogs

This author wrote on Sept 2022: "When treated with 150 mg nilotinib, it failed to provide an improvement in motor ability and CSF biomarker levels, possibly because the low concentration of nilotinib accumulated in the brain is not sufficient to inhibit c-Abl. Previous preclinical studies found that low doses of nilotinib had the ability to inhibit c-Abl, improve motor outcomes and CSF biomarker levels (Hebron et al., 2013a,b, 2014; Pagan et al., 2016). However, nilotinib does not appear these effects clinically because only a maximum of 10% of the concentration thought to be adequate to inhibit c-Abl was detected in the brain of PD patients (Pagan et al., 2019; Werner and Olanow, 2022). This may be interpreted by ATP-binding cassette (ABC) transporters which facilitate nilotinib removal from brain, therefore, nilotinib hardly achieves effective concentration to inhibit c-Abl. In addition, the duration of nilotinib to inhibit c-Abl in the brain is 6 hours, (Pagan et al., 2016) once-daily administration can not sustain the effect throughout the day.

When treated with 300 mg nilotinib, we found a conflict result that nilotinib could significantly worsen motor ability but significantly decrease α-synuclein levels and increase DOPAC levels, which was inconsistent with previous studies. These studies had demonstrated that nilotinib could accelerate autophagic clearance to degrade α-synuclein accumulated in the cells, protect dopaminergic neurons, increase dopamine and its metabolity DOPAC levels, and result in a motor improvement (Hebron et al., 2013a, 2014; Karuppagounder et al., 2014; Lonskaya et al., 2014; Wu et al., 2021). This confounding result between dose-dependent motor disability and improvement in CSF biomarker levels in our study may be due to the fact that all patients in three included studies were diagnosed with PD over 10 years with least H/Y stage 2 and all of them were treated with the concurrent chronic levodopa therapy. The ELLDOPA study, which aimed to assess the effect of levodopa on the progression of PD for a period of 42 weeks, found that levodopa significantly improved UPDRS scores in a dose-dependent manner, but this effect gradually diminished, eventually, UPDRS III worsened compared with baseline (Fahn et al., 2004). One of the potential mechanisms related to this variable effect may be the dopamine neurotoxicity caused by dopamine metabolites 2,4,5trihydroxyphenylalanine (TOPA) and TOPA-quinone, (LeWitt, 2015) which may counterbalance the neuroprotective effect of nilotinib. Nilotinib enters the brain through the blood-brain barrier in a dose-independent manner, and its inhibition of c-Abl is equivalent to that of 150 mg (Pagan et al., 2019). It is possible that the detrimental effects of chronic levodopa therapy on motor outcomes may conceal the minor clinical benefits of nlotinib on the inhibition of c-Abl, which may be an interpretation for this conflict."

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Discogs_discogs in reply to Discogs_discogs

... And:

"Conclusion. 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 bad efficacy on motor outcomes indicated that nilotinib had no advantages in the clinic. These findings from three small sample-size trials should not be applied to a larger population. And stronger evidence from large-sample, well-designed trials in patients without chronic levodopa treatment is needed in the future."

PDWarrior1900 profile image
PDWarrior1900

wow! fun! more supplements to add to my 40+ now! LOL

thanks for the post bolt (no sarcasm, there)

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