This is one of the posts I removed when I got pissed and left the board after a serious disagreement. I think it suits this thread well, so maybe it's worth reposting:
It is not just hype, and it has not come out of nowhere. The research history of minocycline as a neuroprotective agent is a combination of creative thinking, hard work and a bit of luck:
1998 - Minocycline is found to be neuroprotective in an animal model of stroke
In 1998 a group of Finnish researchers finds out that "lipid-soluble tetracyclines, doxycycline and minocycline, inhibit inflammation and are neuroprotective against global ischemia in gerbils"
. In 1999 group leader Jari Koistinaho
states in a major Finnish newspaper that minocycline is effective in preventing disability caused by stroke in an animal model, and it should be tested in a clinical trial. Unfortunately - as far as I know - no such trial has been conducted in Finland yet.
2001 - Minocycline is found to be neuroprotective in a cell culture of ALS
Finnish researcher Tiina Tikka, who worked in the team that studied minocycline in ischemia stroke, also studies minocycline in cell cultures of cerebrospinal fluid from patients with ALS. Her doctoral thesis is based on the positive findings of the study, and is titled "Neuroprotective Effects of Tetracycline Derivates in Primary Cell Culture Models of Excitotoxicity and Inflammation"
(abstract is only in Finnish, sorry).
2001 - Minocycline reduces the severity of EAE in mice
A team of American and German researchers lead by Dr Ian Duncan
discovers that minocycline can reduce the severity of EAE in mice
. Duncan says that his team considered trying minocycline to treat MS because "Finnish studies had shown the antibiotic stopped the activation of microglial cells, which patrol the brain and respond to immune events, in stroke patients".
2001 - First clinical trial of minocycline in MS is to be started in Canada
"The Canadian Institutes of Health Research (CIHR) announced funding of more than $5 million over five years for a study of the role that enzymes called matrix metalloproteinases (MMPs) have in multiple sclerosis. This interdisciplinary study headed by Dr. V. Wee Yong of the University of Calgary will focus on all aspects of MMPs from the environmental, biological and therapeutic aspects and involve researchers at five different universities. Part of the study will be a Phase I clinical trial of the common acne medication minocycline in relapsing-remitting MS."
(MS Society of Canada, Medical Update Memo
"We chose minocycline since it anecdotally appeared to improve the condition of MS patients who were using it for acne relief and later determined the important effect of minocycline as an MMP inhibitor."
(MMPs in MS, Canada
2002 - First clinical trial of minocycline in ALS is conducted in the USA
is conducted at California Pacific Medical Center in San Francisco. Its results show that high doses of minocycline appears to be safe and well tolerated by patients with ALS. The study was not designed to test effectiveness of the drug in ALS. Larger, multicenter study of minocycline for ALS is started in 2003 and is under way.
2003 - Minocycline is now studied in a broad range of neurological disorders
A team of Harvard Medical School researchers
states that "minocycline, a semisynthetic tetracycline, has demonstrated remarkably broad neuroprotective properties in experimental models of ischemic stroke, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, multiple sclerosis, and Parkinson's disease".
2003 - Preliminary results of the MS trial are presented at the AAN meeting
"At the AAN meeting, scientists reported on the first clinical trial of minocycline in MS (3). Ten patients with active relapsing-remitting MS were enrolled in the study. After a three-month observation period, treatment was initiated with minocycline by mouth twice daily. Whereas prior to treatment, 80% of patients had active MS by MRI scanning, none of the treated patients have shown subsequent MRI evidence of activity, as much as nine months later. There have been no safety concerns. It is likely that larger MS trials of minocycline will be initiated over the next year."
2004 - Minocycline is found to produce neuroprotection in MS
Dr V. Wee Yong
, who is responsible for the Canadian minocycline trial together with Dr Luanne Metz
, suggests in an article "the prospect of an experimental treatment, minocycline, in producing neuroprotection in MS"
. In the article he also evaluates "the possibility that glatiramer acetate (Copaxone) enables neuroprotection in MS through beneficial inflammation".
2004 - Results of the MS trial are presented in the may issue of Annals of Neurology
Selected quotes from the letter titled "Minocycline Reduces Gadolinium-Enhancing Magnetic Resonance Imaging Lesions in Multiple Sclerosis"
"We report a trial of minocycline in people with relapsingremitting multiple sclerosis (RRMS) that evaluates safety and estimates its effect on magnetic resonance imaging (MRI). Ten subjects with active RRMS received oral minocycline 100mg twice daily for 6 months after a 3-month run-in period. A 30-month treatment extension is ongoing."
"During the trial, there were no serious adverse events or laboratory abnormalities and no change in EDSS."
"There were no active scans after month 2 (Fig) and no new active lesions after month 1. Although five patients accounted for all MRI activity before and after treatment, all patient data were included in all analyses."
"Small sample size and short trial duration limit conclusions, but reduced MRI activity is encouraging and calls for definitive studies to establish minocycline efficacy in MS."
(Annals of Neurology, page 756)
2004 - Minocycline will be tested in a clinical trial together with Copaxone
Teva Pharmaceutics, the manufacturer of Copaxone, is sponsoring the future trial. Maybe the combination therapy will be more effective than either of the drugs alone, but hopefully the researchers get a change to test minocycline also as monotherapy.
Is minocycline a novel way to treat MS?
In my opinion, yes. It has anti-inflammatory properties like all current treatments, but the key issue with minocycline is neuroprotection. According to an Australian study
the first sign of new MS attack could be the death of oligodendrocytes (myelin making cells)
, and it is the programmed cell death that triggers the autoimmune reaction shown as active MRI lesions. It might be possible that during the clinical trial neuroprotective properties of minocycline were even able to lessen the amount of dying oligodendrocytes, which then showed as a lack of new autoimmune reactions and MRI activity in all
It won't be a miracle drug, but it might as well be able to protect our body from further damage caused by MS better than any of the current treatments. Unfortunately it probably will take years before we know it for sure.
(originally posted may 2004)