Malfitano AM, Marasco G, Proto MC, Laezza C, Gazzerro P, Bifulco M. Statins in neurological disorders: an overview and update.Pharmacol Res. 2014 Jun 19. pii: S1043-6618(14)00099-1. doi: 10.1016/j.phrs.2014.06.007. [Epub ahead of print]
Statins have, at present, the potential to provide a new therapeutic target for various neurological diseases. It is well established that statins reduce cholesterol levels and prevent coronary heart disease. Moreover, evidence suggest that statins have additional properties such as endothelial protection via action on the nitric oxide synthase system as well as antioxidant, anti-inflammatory and anti-platelet effects. These properties might have potential therapeutic implication not only in stroke, but also in neurological disorders such as Alzheimer disease, Parkinson’s disease, multiple sclerosis and primary brain tumors. In addition to their potent anti-atherosclerotic and cardio-protective effects, compelling clinical and preclinical studies delineate the neuro-protective efficacy of statins in all these neurological disorders. It is apparent from these studies that most patients with central nervous system disorders probably benefit to some extent from lipid-lowering therapy. But data are not univocal, and we must also consider the adverse effects due to the administration of lipid-lowering therapy. Thus, in these scenarios the effectiveness of statins in treating stroke, Alzheimer’s disease, Parkinson disease, multiple sclerosis, and primary brain tumors have to be conclusively proven in vivo and/or in adequate clinical trials.
So we have had trials and the data don’t tell us enough about dose and efficacy and we need more trials
So the question we have been asking is who are going to fund these trials? and even if they are funded then what? What is the pathway to prescription?.
I think too little thought is given to this critical question, because without the right answer the studies will falter and go nowhere. This is the question that the ethical committees need to ask and not accept some stock-answer
Do academics believe that the regulatory system, they helped create to give pharma a toughtime, will bend for them…
Do we need to talk to pharma to see if they have a new statin on the shelf that they can take into phase III, because this is perhaps part of the benefit of these trials as it shows pharma what to do and what not to do in their trials and it identifies targets.
Will they go down the HMG-CoA pathway to get new drugs. Maybe they are doing this already and we don’t know
Whilst this post may seem directed at Sir Jeremy and related neuros that gave use the statin conundrum, it is not. It is a problem for others (academic neuros) including ProfG who are doing studies with other repurposed drugs.
MS SMART is starting with Amiloride (Patent filed with MRC-WO2008007131…so MRC hopefully have been paying since 2006 to keep that alive); Ibudilast there is company behind this one Medicinova…so interesting that there are two academic led trials going on? The original Japanese patent was from 1998 and, riluzole (There is a patent filed in 1998, but I suspect company interest in this has expired…When ProfG and I tried to get this trialled in progressive MS in about 2001/2002 a certain company (or should I say the accountants of a certain company) weren’t interested…I think this was too early for the approach. If we had gone back 5-10 years later the penny may have dropped. Sometimes you can be too far ahead of the curve. Now it may be too late for the approach.
The purpose of this post is to say that we have to think what’s next. There is not point in starting without this thought.
This requires planning and maybe action, certainly by the medical fraternity, funders of studies but also people power.
Maybe if we can make progressive MS an orphan disease by the time trials are finished you would only need one phase III trial and so lower the hurdle that academic groups face to get drugs to pwMS. This would also help pharma too.