Progress and Prospects in Parkinson's Research/Therapy/Neuroprotection/Minocycline

"The results of tests on the neuroprotective qualities of minicycine to date are ambiguous."

Background
Minocycline (INN) is a broad-spectrum tetracycline antibiotic,

Research
2001

Du et al tested the neuroprotective properties of minocycline and found that;-


 * It prevents nigrostriatal dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease.
 * It also blocked dopamine depletion in the striatum as well as in the nucleus accumbens after MPTP administration.

2003

Yang et al measured the effect of minocycline on rats with Parkinsonism induced by MPTP.

"We found that although minocycline inhibited microglial activation, it significantly exacerbated MPTP-induced damage to DA neurons. We present evidence suggesting that this effect may be due to inhibition of DA and 1-methyl-4-phenylpridium (MPP+) uptake into striatal vesicles."

2004

Diguet et al tried different doses of minocycline on Parkinsonian mice and monkeys with a range of results. Some improved and some worsened. Their conclusion:-

"Minocycline may have variable and even deleterious effects in different species and models according to the mode of administration and dose."

2006

NINDS NET-PD Investigators Creatine and minocycline were prioritized for testing in Phase II clinical trials based on a systematic evaluation of potentially disease modifying compounds for Parkinson's disease.

The conclusion was that both creatine and minocycline should be considered for definitive Phase III trials to determine if they alter the long term progression of Parkinson's disease.

Quintero et al observed the effects of treatment of 6-OHDA Parkinsonian rats with timed doses of minocycline. Their conclusions:-

"These data suggest that the therapeutic potential of minocycline may depend on the time of drug administration relative to neuropathogenic event."

2009

Faust et al reported on a series of tests with fruit flies.

"In the present study, a Drosophila DJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection in Drosophila DJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level."

2010

Radad et al Treated mice, who were rendered Parkinsonian with the application of rotenone, with minocycline. Their conclusions:-

"Minocycline has neuroprotective potential against the progressive loss of tyrosine hydroxylase immunoreactive neurons induced by long-term rotenone toxicity in primary dopaminergic cultures."