Parkinson's Disease Tulip


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Old 05-04-2017, 09:52 AM #1
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Default Doxycycline For Treatment Of PD

https://www.sciencedaily.com/release...0503134119.htm
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Old 05-06-2017, 12:42 AM #2
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From the research paper:
"The results presented herein reveal potential protective side effects for doxycycline in the pathogenesis cycle of synucleinopathies that could be exploited repurposing an old safe drug."
"This data strongly suggests that doxycycline in subantibiotic doses (20–40 mg/day) would be enough to exert neuroprotection."

From the ScienceDaily article:
"This treatment could stop Parkinson's from progressing, and we therefore plan to start a clinical trial shortly."

Could this be another clinical trial worthy of a fast-track process?

Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species : Scientific Reports

(this is an open-access research paper)
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Old 05-06-2017, 03:32 AM #3
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An impressive piece of biophysics and cell biology.

I think that the comments in the link are worth considering.
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Old 05-06-2017, 07:22 AM #4
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Well spotted, kiwi33. I missed those comments, and they are significant.

It would seem that a fast-tracked clinical trial would not be appropriate.
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Old 05-06-2017, 09:09 AM #5
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Quote:
Originally Posted by jeffreyn View Post
From the research paper:
"The results presented herein reveal potential protective side effects for doxycycline in the pathogenesis cycle of synucleinopathies that could be exploited repurposing an old safe drug."
"This data strongly suggests that doxycycline in subantibiotic doses (20–40 mg/day) would be enough to exert neuroprotection."

From the ScienceDaily article:
"This treatment could stop Parkinson's from progressing, and we therefore plan to start a clinical trial shortly."

Could this be another clinical trial worthy of a fast-track process?

Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species : Scientific Reports
Interesting that you feel this way. When I first read this article back in February I wasn't overly impressed. Certainly no more than with the dozens of other pre-clinical studies that have "cured" PD. I was surprised when it received so much press recently. When I saw your post, it made me go and reread the research. I still don't see why this study would call for a fast-designation on future research anymore than the dozens of other drugs, both new and repurposed, that have shown pre-clinical success. I also would have some concern about a treatment which requires the long term use of an antibiotic. What am I missing here?
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Old 05-06-2017, 09:11 AM #6
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Quote:
Originally Posted by jeffreyn View Post
Well spotted, kiwi33. I missed those comments, and they are significant.

It would seem that a fast-tracked clinical trial would not be appropriate.
Thanks Kiwi. Sorry jeffreyn, I guess I should have read through all of the posts before making my comments.
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Old 05-06-2017, 10:15 PM #7
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No worries, Tupelo3.

When I wrote those words, I had in the back of my mind the recent discussions about the desirability of speeding up the clinical-trials phase for PD drugs in general. So it wasn't that this one stood out particularly (although it did seem like a good candidate), it was more that I'd lowered the bar!

The question mark at the end was (secret?) code for "I'm interested in a discussion". :-)

But after that, kiwi33 alerted me to some expert comments, which shed new light on things.
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Old 05-09-2017, 08:49 AM #8
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Default Curcumin

From the same paper, curcumin is mentioned. While everyone waits for re-purposed drugs to make it out of these trials, maybe curcumin could help now.

Curcumin (diferuloylmethane) also reduces significantly cell toxicity of α-Syn aggregates by binding to preformed oligomers and fibrils46 with effectiveness comparable with doxycycline (1:1 molar ratio)47. However, the instability, low solubility, little oral bioavailability of curcumin limit its clinical applications and to overcome this drawback, some structural curcumin analogues with antiaggregation properties are been developed. In this context, no human long-term toxicity studies have been reported until now with curcumin structural analogues48. On the contrary, oral administration of doxycycline proved to be a safe and effective drug for dermatologically long-term treatments49,50. Moreover, it was also reported that sub-antibiotic doses of doxycycline have no effect on the composition or antibiotic resistance of different microflora51.
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Old 05-09-2017, 05:31 PM #9
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Quote:
Originally Posted by ashleyk View Post
From the same paper, curcumin is mentioned. While everyone waits for re-purposed drugs to make it out of these trials, maybe curcumin could help now.

Curcumin (diferuloylmethane) also reduces significantly cell toxicity of α-Syn aggregates by binding to preformed oligomers and fibrils46 with effectiveness comparable with doxycycline (1:1 molar ratio)47. However, the instability, low solubility, little oral bioavailability of curcumin limit its clinical applications and to overcome this drawback, some structural curcumin analogues with antiaggregation properties are been developed. In this context, no human long-term toxicity studies have been reported until now with curcumin structural analogues48. On the contrary, oral administration of doxycycline proved to be a safe and effective drug for dermatologically long-term treatments49,50. Moreover, it was also reported that sub-antibiotic doses of doxycycline have no effect on the composition or antibiotic resistance of different microflora51.
http://www.longvida.com/story.html might be the answer to low bioavailability curcumin.
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Old 06-04-2017, 04:34 PM #10
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I started taking 20 mg a day of Doxy about a week ago. So far, no observable effects.
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