A tetracycline called minocycline has pulished research (300+ papers) going back over ten years with very positive results. Yet, no one seems to use it. PLM doesn't list a single soul on it. It seems to have a good safety profile, gets past the BBB, and is a great anti-inflammatory (prevents microglial activation).

So why do we never hear of it? No money to be made?


1. Curr Pharm Des. 2004;10(6):679-86.

Minocycline: neuroprotective mechanisms in Parkinson's disease.

Thomas M, Le WD.

Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
weidongl@bcm.tmc.edu

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
cardinal features of tremor, bradykinesia, rigidity and postural instability. In
addition to the motor symptoms patients experience cognitive decline eventually
resulting in severe disability. Pathologically PD is characterized by
neurodegeneration in the substantia nigra pars compacta (SNc) with
intracytoplasmic inclusions known as Lewy bodies. In addition to the SNc there is
neurodegeneration in other areas including cerebral cortex, raphe nuclei, locus
ceruleus, nucleus basalis of meynert, cranial nerves and autonomic nervous
system. Recent evidence supports the role of inflammation in Parkinson's disease.
Apoptosis has been shown to be one of the pathways of cell death in PD.
Minocycline, a tetracycline derivative is a caspase inhibitor, and also inhibits
the inducible nitric oxide synthase which are important for apoptotic cell death.
Furthermore, Minocycline has been shown to block microglial activation of
6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned
parkinsonism animal models and protect against nigrostriatal dopaminergic
neurodegeneration. In this review, we present the current experimental evidence
for the potential use of tetracycline derivative, minocycline, as a
neuroprotective agent in PD.


PMID: 14965330 [PubMed - indexed for MEDLINE]


1. Behav Brain Res. 2009 Jan 23;196(2):168-79. Epub 2008 Oct 11.

Minocycline and neurodegenerative diseases.

Kim HS, Suh YH.

Department of Pharmacology, Seoul National University, College of Medicine,
Seoul, Republic of Korea.

Minocycline is a semi-synthetic, second-generation tetracycline analog which is
effectively crossing the blood-brain barrier, effective against gram-positive and
-negative infections. In addition to its own antimicrobacterial properties,
minocycline has been reported to exert neuroprotective effects over various
experimental models such as cerebral ischemia, traumatic brain injury,
amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment,
Huntington' disease and multiple sclerosis. Minocycline has been focused as a
neuroprotective agent over neurodegenerative disease since it has been first
reported that minocycline has neuroprotective effects in animal models of
ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J.
Tetracyclines inhibit microglial activation and are neuroprotective in global
brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T,
Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative,
minocycline, reduces inflammation and protects against focal cerebral ischemia
with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500].
Recently, the effect of minocycline on Alzheimer's disease has been also
reported. Although its precise primary target is not clear, the action mechanisms
of minocycline for neuroprotection reported so far are; via; the inhibition of
mitochondrial permeability-transition mediated cytochrome c release from
mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression
of microglial activation, involvement in some signaling pathways, metalloprotease
activity inhibition. Because of the high tolerance and the excellent penetration
into the brain, minocycline has been clinically tried for some neurodegenerative
diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic
lateral sclerosis, Hungtington's disease and Parkinson's disease. This review
will briefly summarize the effects and action mechanisms of minocycline on
neurodegenerative diseases.


PMID: 18977395 [PubMed - indexed for MEDLINE]

Rick, they did a trial with this for ALS some time ago and it appeared to shorten life span, so they nixed it. Now, perhaps if they used a lower dose, or higher, or whatever, the outcome may have been different. We can always learn from the failures and totally scrapping something may not always be best.

Aside from that, though, I think there is a lot of hesitation to look at things that, over time, can have some pretty serious side effects. I know, I know, like sinemet doesn't, but we don't have an Rx alternative to sinemet, and current thinking is that PWP don't have a choice in taking it (kudos to those who are strictly going the alternative route and I really hope it works for you), but those folk are not the majority. Heck, most neuros haven't even heard of most of the stuff talked about here.

I wish someone would look at exactly WHY minocycline helps and go at it from that angle. Has anyone used it and noticed an improvement with their PD symptoms?

We have discussed a few times the "amazing" effect of short term antibiotic use as reported anecdotally. Penicillin VK has been mentioned. The action seems to be anti-inflammatory.

What puzzles me is why there is no effort to reproduce these short term results as a stepping stone toward a long term use. If we go to our GP tomorrow with a UTI, he won't hesitate a second to whip out his prescription pad and give us a couple of weeks worth. Yet, they don't seem to see any value in doing exactly the same thing to move this onto the board.

Yep, we're saying the same thing. They (researchers) need to look at the fact that anti-inflammatories seem to help more than a coincidental few PWP and then look at why, what is the mechanism? I seem to remember, however, that after awhile, the "amazing" effects seemed to wear off...leaving one to wonder, what happened, and why? Did the body build up an immunity to the anti-inflammatory? Did things get as uninflamed as they could get?

Along this line, haven't they now shown than NSAIDS are not as helpful to PWP as once thought? We read some articles awhile back indicating they might even be neuroprotective, ha. If inflammation were IT, I would think NSAIDS would have shown a lot more potential than they currently have.

Maybe we have just not found the right anti-inflammatory in the right dose yet. Still, the fact that so many PWP have had pretty remarkable symptomatic relilef while on this or that antibiotic does scream for more inquiry.

And yes, we can all get a script for one of these, but for how long? That's the problem. Anyone know a doc who would be willing to give you a prescription for minocycline for six months (to see if things improved) when you don't have a known infection?

The problem of initial success that then dissipates is one that crops up repeatedly with PD. I suspect it is a case of the Western view of if a little is good then a little more is better. Many things don't adhere to this rule. Turmeric, DXM, ashwagandha, ginger - all show this effect. There may be something about the CNS that responds to a nudge but not to a shove.

There are some preliminary trials being done by NIH but we'll be history before that bears fruit. Living in farm country I have the option of buying tetracycline off the shelf and may do so at some point.

I would urge anyone who takes a round of antibiotics and notices any change to post the details.

ScienceDaily (Sep. 9, 2010) — One of the antibiotics most commonly prescribed to treat adolescent acne can increase attention spans and communication and decrease anxiety in patients with fragile X syndrome, the most common inherited cause of mental impairment, according to a new survey study that is the first published on parents' reports of their children's responses to treatment with the medication....
"Minocycline Treatment in Patients with Fragile X Syndrome and Exploration of Outcome Measures" is published in the September 2010 issue of the American Journal of Intellectual and Developmental Disabilities. In the study, parents relate that after being treated for an average of three months, their children showed improvements in their use of language, attention levels and behavior, while experiencing mostly mild side effects....
http://www.sciencedaily.com/releases...0908160352.htm