[reverett123]

One week ago I began exploring the possibilities of antibiotics such as the tetracyclines. Doxycycline hyclate, in particular. At 100 mg 2X daily I have 30 days worth. Some of you oldtimers may remember a few discussions when PWP reported a great improvement in their PD symptoms while taking particular antibiotics, only to have them return once the antibiotics wore off. You may also remember The Strange Case of Ron's Tooth. It sounds like a Sherlock Holmes story but is, in reality, the tale of a simple abcess that caused Ron pain and was removed for its temerity. Its removal was expected to cause the toothache to quickly fade away but, while the pains passed the PD did anything but and Ron was bed ridden for two weeks for no apparent reason.

These are hints at the true nature of PD as an inflammatory condition IMHO. The antibiotics that seem to work lead a rare double life as BBB penetrating, fat (brain) soluble anti-inflammatories completely divorced from their anti-bacterial role. As a result they go deep into the CNS and quench the fire there.

At least that's the theory. I have suspended other experiments with green tea extract for now and will continue this for the month. So far it looks promising. Meds down about 25%. Function up, particularly in the afternoon, a bad time for me. And something a little unusual. I had two teeth extracted last week. The dentist, on the followup visit Friday was a little surprised to find that my gum tissues was doing so well. No swelling at all and no pain. Rapid healing. I'll keep you posted.

[sim00]

Thank you so much for sharing your experience.

[johnt]

Coincidently I've been on antibiotics for the past week:
1x500mg, Flucloxacillin four times a day;
2x250mg, Penicillin V, four times a day.
(I'm taking them to help fight a foot infection.) The last week has been one of my best PD-wise for months: looser, more lively, better balance (but, still bad tremor).

My side-to-side tap test scores, at least 12 hours after my last dose of levodopa (but still benefitting from the controlled release agonist) have averaged about 36, as opposed to my normal 30.
( The results come from:
http://www.parkinsonsmeasurement.org...eToSideTap.htm
The figures given are the sum of left hand and right hand movements, with each measured over 30 sec.)

I find it difficult to reconcile the reports of reduced symptoms following antibiotic treatment with the idea that a major part of the aetiology of PD is the death of dopaminergic neurons: if they were dead, how can the antibiotic lead to more dopamine?

It seems to me to fit a continuous assault theory better: bacteria in the gut produce toxins which get through to the brain, where for some time before the dopaminergic cells die, they reduce the amount of dopamine produced. Here, by killing bacteria, the antibiotic reduces the amount of toxin being produced, leading to better dopamine production.

When my course of antibiotics is over I intend to take large amounts (about a litre per day) of homemade probiotic yogurt, in order to replenish some of the damage done by the antibiotics.

John

[reverett123]

[QUOTE=johnt;868199]Coincidently I've been on antibiotics for the past week:
1x500mg, Flucloxacillin four times a day;
2x250mg, Penicillin V, four times a day.
(I'm taking them to help fight a foot infection.) The last week has been one of my best PD-wise for months: looser, more lively, better balance (but, still bad tremor).

My side-to-side tap test scores, at least 12 hours after my last dose of levodopa (but still benefitting from the controlled release agonist) have averaged about 36, as opposed to my normal 30.
( The results come from:
http://www.parkinsonsmeasurement.org...eToSideTap.htm
The figures given are the sum of left hand and right hand movements, with each measured over 30 sec.)


Thanks for adding to the data and its interpretation. First, the dead neurons view is, as I understand it, by no means the slam dunk that we are told it is.
Second, the bacterial theory requires the presumptions of an unidentified bacterium in the gut producing an undetected toxin capable of penetrating the BBB and interferring with dopamine for an indefinite time before being either neutralized or killing only neurons in the SN etc. Too messy. Contrast it with a hyper immune response beyond the BBB (known) that originated in the womb (known) and once started ran for months longer than it should (known). Add in that a similar sensitivity can start later in life from exposures to flu (known) or at middle age due to a natural increase with age (known). The observed reaction adds a dozen inflammatory chemicals to the brain environment (known) which lead to cell death (known) rather than killing cells outright and therefore more subtle. Most importantly from our standpoint is that these chemicals are themselves neuroactive and are neurotransmitters affecting behavior in major ways (known). Finally, all this chaos is tamped down or even eliminated by antibiotics, but only those known to have the ability to pass the BBB and counteract the chemical cocktail.

The reason I harped on that so much is that if a large part of our symptoms are the result of inflammation then PWP can go to the pharmacy tomorrow and choose a whole new way of relieving them just as you have done. Not five years - tomorrow! And not some high dollar side effect laden mess but instead some of the oldest and most studied and cheapest things on the shelf.

So. Is it possible for us to use our experiences in some way to prove or disprove any of this? To actually take a big step against PD that others can expand on?

I find it difficult to reconcile the reports of reduced symptoms following antibiotic treatment with the idea that a major part of the aetiology of PD is the death of dopaminergic neurons: if they were dead, how can the antibiotic lead to more dopamine?

[reverett123]

If you have a good relationship with your GP (preferred) or neuro and would `consider asking his help in doing this, I would be happy to put together a package of scientic reports explaining the whole thing and why he or she should help. Just a month of an antibiotic that is handed out by the handful everyday to treat kid's pimples. If it works for you then you can discuss a refill. It is long past time that we took responsibility for "our" disease.

[Jim091866]

Rick are you suggesting amoxicillin for a trial or tetracycline for its anti inflammatory properties? I'm thinking of trying this.

[reverett123]

Originally Posted by Jim091866

Rick are you suggesting amoxicillin for a trial or tetracycline for its anti inflammatory properties? I'm thinking of trying this.

Jim-
I won't suggest anything since I honestly don't know at this point. However, it would seem that a sensible strategy would be to follow me down the doxycycline trail which would allow the comparison of our individual experience of a common phenomenon. We can let future generations work through individual compounds themselves. Doxycycline is one of the tetracycline family and is very similar to minocycline, another family member frequently mentioned in this context. While side effects are rare, the possible ones for the latter are more intimidating than those for the former. Both cross the BBB and are fat-soluble and anti-inflammatory and cheap. Here is some home work for you-
On the role of inflammation in PD-

1. Neurobiol Dis. 2010 Mar;37(3):510-8. Epub 2009 Nov 10.

Neuroinflammation in Parkinson's disease: its role in neuronal death and
implications for therapeutic intervention.

Tansey MG, Goldberg MS.

Department of Physiology, Emory University School of Medicine, 615 Michael
Street, Atlanta, GA 30324, USA. malu.tansey@emory.edu

Parkinson's disease (PD) is the second most common neurodegenerative disease,
after Alzheimer's disease. The potential causes of PD remain uncertain, but
recent studies suggest neuroinflammation and microglia activation play important
roles in PD pathogenesis. Major unanswered questions include whether protein
aggregates cause the selective loss of dopaminergic neurons in the substantia
nigra that underlies the clinical symptoms and whether neuroinflammation is a
consequence or a cause of nigral cell loss. Within the microenvironment of the
brain, glial cells play a critical role in homeostatic mechanisms that promote
neuronal survival. Microglia have a specialized immune surveillance role and
mediate innate immune responses to invading pathogens by secreting a myriad of
factors that include, cytokines, chemokines, prostaglandins, reactive oxygen and
nitrogen species, and growth factors. Some of these factors have neuroprotective
and trophic activities and aid in brain repair processes; while others enhance
oxidative stress and trigger apoptotic cascades in neurons. Therefore, pro- and
anti-inflammatory responses must be in balance to prevent the potential
detrimental effects of prolonged or unregulated inflammation-induced oxidative
stress on vulnerable neuronal populations. In this review, we discuss potential
triggers of neuroinflammation and review the strongest direct evidence that
chronic neuroinflammation may have a more important role to play in PD versus
other neurodegenerative diseases. Alternatively, we propose that genetic
deficiency is not the only way to reduce protective factors in the brain which
may function to keep microglial responses in check or regulate the sensitivity of
DA neurons. If chronic inflammation can be shown to decrease the levels of
neuroprotective factors in the midbrain, in essence genetic haploinsufficiency of
protective factors such as Parkin or RGS10 may result from purely environmental
triggers (aging, chronic systemic disease, etc.), increasing the vulnerability to
inflammation-induced nigral DA neuron death and predisposing an individual to
development of PD. Lastly, we review the latest epidemiological and experimental
evidence supporting the potential use of anti-inflammatory and immunomodulatory
drugs as neuroprotective agents to delay the progressive nigrostriatal
degeneration that leads to motor dysfunction in PD.

2009 Elsevier Inc. All rights reserved.

PMCID: PMC2823829
PMID: 19913097 [PubMed - indexed for MEDLINE]

Note: Free full text is available.

---------------


1. Prog Neurobiol. 2009 Nov;89(3):277-87. Epub 2009 Aug 15.

The influence of microglia on the pathogenesis of Parkinson's disease.

Long-Smith CM, Sullivan AM, Nolan YM.

Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Parkinson's disease (PD) is characterised by degeneration of dopaminergic neurons
in the substantia nigra pars compacta (SNpc). Inflammation may be associated with
the neuropathology of PD due to the following accumulating evidence: excessive
microglial activation and increased levels of the pro-inflammatory cytokines
tumour necrosis factor-alpha and interleukin-1beta in the SNpc of patients with
PD; the emergence of PD-like symptoms following influenza infection; the
increased susceptibility to PD associated with bacterial vaginosis; the presence
of inflammatory mediators and activators in animal models of PD; the ability of
anti-inflammatory drugs to decrease susceptibility to PD; and the emerging
possibility of the use of microglial activation inhibitors as a therapy in PD. In
this review, we will discuss the role of inflammation in PD. We will focus on the
influence of microglia in the pathogenesis of PD and discuss potential
therapeutic interventions for PD, that target microglia.

PMID: 19686799 [PubMed - indexed for MEDLINE]

---------------


1. Br J Pharmacol. 2007 Apr;150(8):963-76. Epub 2007 Mar 5.

Inflammation as a causative factor in the aetiology of Parkinson's disease.

Whitton PS.

1Department of Pharmacology, The School of Pharmacy, London, UK.
peter.whitton@pharmacy.ac.uk

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting
mainly the elderly, although a small proportion of PD patients develop the
illness at a much younger age. In the former group, idiopathic PD patients, the
causes of the illness have been the subject of longstanding debate with
environmental toxins, mitochondrial dysfunction, abnormal protein handling and
oxidative stress being suggested. One problem has been that the epidemiology of
PD has offered few clues to provide evidence for a single major causative factor.
Comparatively recently it has been found that in both patients and experimental
models of PD in animals neuroinflammation appears to be a ubiquitous finding.
These cases present with all of the classical features of inflammation including
phagocyte activation, increased synthesis and release of proinflammatory
cytokines and complement activation. Although this process is vital for normal
function and protection in both the CNS, as in the periphery, it is postulated
that in the aetiology of PD this process may spiral out of control with over
activation of microglia, over production of cytokines and other proinflammatory
mediators as well as the release of destructive molecules such as reactive oxygen
species. Given that dopaminergic neurons in the substantia nigra are relatively
vulnerable to 'stress' and the region has a large population of microglia in
comparison to other CNS structures, these events may easily trigger
neurodegeneration. These factors are examined in this review along with a
consideration of the possible use of anti-inflammatory drugs in PD.

PMCID: PMC2013918
PMID: 17339843 [PubMed - indexed for MEDLINE]

Full text available

[ScottSuff]

I was feeling the effects of the heavy East TN pollen and it got down in my chest. A trip to the doc got me a 10 day supply of Cipro and a steroid. For over two weeks now I've had the best on time with meds than I've had in a long time. Got to be something to the inflammation theory!

[moondaughter]

Originally Posted by ScottSuff

I was feeling the effects of the heavy East TN pollen and it got down in my chest. A trip to the doc got me a 10 day supply of Cipro and a steroid. For over two weeks now I've had the best on time with meds than I've had in a long time. Got to be something to the inflammation theory!

Ditto with pollen presence in eastern OR - Kyolic garlic , astragalus and vit C are also extending my med - quercitin coming in the mail!

[reverett123]

The past two days the GI factor has made itself known and the PD symptoms have worsened slightly (poorer quality of on time). I am going to back off a day or two and let all the bugs settle down. Presumably that will also improve the PD symptoms.

It still looks promising in that I had a week of moderate improvement of on time. It would be interesting to know what a different antibiotic might do, as well as a different rat. I also think that the exploration of other anti-inflammatories that can get past the BBB might be rewarding.
Gotta go..........