OBJECTIVE: To determine whether statins affect type 1 interferon responses in RRMS.
DESIGN: Study effects of atorvastatin on type 1 interferon responses in Jurkat cells, mononuclear cells (MNCs) from therapy-naive MSers with RRMS in vitro , and MNCs from interferon-treated RRMS MSers in vivo in 4 conditions: no drug, statin only, interferon-beta only, and statin added on to interferon-beta therapy.
PATIENTS: The study examined clinically stable MSers with RRMS: 21 therapy-naive MSers and 14 MSers receiving interferon-beta with a statin.
INTERVENTIONS: Statin effects on in vitro and in vivo interferon-beta-induced STAT1 transcription factor activation, expression of interferon-stimulated proteins in MNCs, and serum type 1 interferon activity.
RESULTS: In vitro, atorvastatin dose dependently inhibited expression of interferon-stimulated P-Y-STAT1 by 44% (P = 0.001), interferon regulatory factor 1 protein by 30% (P = .006), and myxovirus resistance 1 protein by 32% (P = .004) compared with no-statin control in MNCs from therapy-naive RRMS MSers. In vivo, 9 of 10 MSers who received high-dose statins (80 mg) had a significant reduction in interferon-beta therapy-induced serum interferon-α/β activity, whereas only 2 of 4 patients who received medium-dose statins (40 mg) had reductions. High-dose add-on statin therapy significantly blocked interferon-beta function, with less P-Y-STAT1 transcription factor activation, and reduced myxovirus resistance 1 protein and viperin protein production. Medium doses of statins did not change STAT1 activation.
CONCLUSIONS: High-dose add-on statin therapy significantly reduces interferon-beta function and type 1 interferon responses in RRMS MSers. These data provide a putative mechanism for how statins could counteract the beneficial effects of interferon-beta and worsen disease.
“Statins are a group of drugs that are prescribed to lower cholesterol. They have a wide range of biological effects outside of cholesterol and lipid metabolism.”
“This data provides experimental evidence why and how statins interfere with the action of interferon-beta and reduce its efficacy.”
“There is a lession here. When the data emerge that statins may be beneficial in MS a lot of MSers went onto statins off label, i.e. added a statin onto their existing therapies. This data indicates that this was not a good idea. This principle should apply to all add-on combination therapies; unless we have data we should assume something is going to be effective until we have studied the combination in the clinical and lab.”
Is it a coincidence that all non-DMT related studies are also run compared to DMT effect? As an early-stage MSer, after checking latest studies conclusions on poor long-term EDSS change improvement compared to no treatment at all (Dr. H. Tremlett seems to be the only one in the world daring to publish such studies), I would much appreciate studies not compared to DMT (eg. Curcumin or Green Tea Extracts current clinical trials are also compared to Interferons. It seems now the australians also dared to run a clinical trial on CIS treated only with D-Vitamin supplements (which by the way a recent study also discussed by you showed that interferons increase D-Vitamin bioavailability in serum blood level- maybe this is their main effect on the disease?)
Its an ethical dilemaYou have a drug that is active albeit modestly active therefore is it ethical to refuse people who would go on placebo something that you know works. This is why add-on to DMT is increasingly likely the way to go.Whilst this can give you a marketing advantage such as campath and beta interferon there is a problem in the pipeline.Problem is once one of the current new DMT (post-interferons) becomes established as a first line it will be then very difficult for someone else to show that a new drugs works better because better efficacy is likely to have more side effect potential.
I can't see why anyone once they manage to get one of the emerging new DMTs would be willing to add-on an injectable without a lot of proof of the benefit (nevermind NICE and the cost). The possibility of adding on one of the oral DMTs with good safety profiles such as teriflunomide or BG12, or a neuroprotectve agent must be the way to go
Yes you are right what I said should have been the way it will go…you are right to say the way to go
Re drug combinations: symptomatic treatments and drugs being given for other conditions could also interfere with DMT action, and these combinations will never be tested