Monday, 30 June 2014

Give us more money to throw down the toilet?

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.   

5 comments:

  1. I'm not sure what this post is telling us - that all the UCLP progressive trials are going to be a waste of time? I've followed this blog for the last 4.5 years and was full of hope. 4.5 years on my hope has faded. Nothing Team G has done has benefitted me (or indeed any other MSers). Lots of pretty graphics and slide shows, but what about my walking, my long term ability to remain in work? This has been a good taking shop, but talk is cheap as they say. Unless you guys are doing trials for pharma, you don't seem to be making any breakthroughs - and if you do, you are prevented from getting any further because of the crazy licensing rules. Charcot project - I won't hold my breath. Progressive MS trials - evidence of a minor slowing of progression, but drugs won't be prescribable, repair - we don't do that. This blg has sapped me of hope - perhaps that was its point!

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    1. This group is only interested in what therapies can be marketed, not what works. The notion that trials connot be conducted without pharma support is false. Its a good thing others are willing and able to investigate what can be done in progressive disease:

      http://clinicaltrials.gov/show/NCT01188811

      How are they able to undertake these studies without the backing of Pharma?

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    2. I am afraid that I believe that you are wrong and may have missed the point.

      There are plenty of clinical trials that are done without pharma involvement. Academics are pretty good at going this. We are doing some of our own

      You mention lipoic acid there have been 87 studies in clinical trial.gov and 7 for MS.
      However, the link you post is "active but not recruiting" which may mean they have the idea but have not got funding to do it.

      It also aims to recruit 28 start 2010 end 2016. The question is then what,.. For a trial of such short duration and low numbers I would think they would struggle to show an effect but lets say it works.....then what.. a free for all and wide spread use?

      Are the regulators going to accept this as definitive evidence that justifies use. I think they would say we need a proper phase III trial and two unless they have are changing the rules for academics over pharma. So another trial taking another 6 years and the regulators want disability as outcome so two year trials are too short and then what?.

      Do the academics etc. have $50,000 to talk to the regulators etc etc.

      If I asked can you name trials of drugs that neuros have done without pharma involvement.. The answer is lots.

      but I ask the question please tell me examples where neuros have developed a drug that is used without pharma involvement...I think it is 0

      What drugs have neuros developed for a non orphan, non-rapidly fatal diseases disease without pharma backing? Examples please.

      Pharma have sued NHS trusts when drugs are used outside their licence

      Nutiriceuticals are not what I am talking about as there appears no burden of proof.
      Vitamin D may be the example.

      I ask these questions because the answers need to be clear. so that academics can indeed develop drugs for pwMS

      Delete
  2. http://www.ncbi.nlm.nih.gov/pubmed/23007702 "Maybe make progressive MS an orphan disease........" but doesn't current research indicate that RRMS, SPMS and PPMS are under similar inflammatory processes leading to gliosis and axonal degeneration with time. It seems that progressive and relapsing disease are often treated as separate processes even though both are still driven by inflammation. Is this correct? Maybe the drugs need to get inside the BBB where they can more effectively control inflammation.

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    1. Well spotted I was thinking of this argument when I was writing this comments.

      You could say perhaps that the perivascular lymphocytic lesions are the basis of relapsing MS and the macrophage/microglia are the substrates for progressive MS. So the progressive phase is present in all MS but it is not treated, as you say the drugs may not get into the brain.

      The point is this there may be a political solution to get changes made to help get pwMS access to treatments. The HIV lobby was very effective at encouraging change. Why not MS?.

      We do not have the time to construct a lobby.

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