Nobel Prize, Jackpot Winner or just Savior?

RxISK is not all about bad news. We ask anyone who is having a problem on a drug to think of a possible use to which this problem could be put. We also want people to keep alert to anything they notice after starting a new treatment.

It is entirely possible that the right set of observations could lead to a Nobel Prize, or might allow someone to take a use patent out on an old drug or might produce a treatment that would save someone else’s life. The best way to discover new drugs is to look very closely at the full range of things that are happening on a drug already on the market.

Come in benztropine

Which is where benztropine comes in.

Many people being treated for Parkinson’s disease or the Parkinsonian side effects of antipsychotics and many nurses of doctors treating them all the way back to the 1970s will know about benztropine – perhaps by its trade name Cogentin. It was one of those drugs everyone knew by its trade name. Technically it’s an anticholinergic drug.

Once it went generic, several companies produced versions of it. There are also many other anticholinergics out there such as procyclidine. The market for these drugs must have shrunk a lot in the 1990s when we stopped prescribing antipsychotics in doses 50 to 100 times what is used now.

So I wasn’t completely surprised when I went to check it up in the drug directory a few weeks ago and found Cogentin was no longer there. Googling it made it clear it had been removed from the market a little over a year ago. Removed in all European countries.

When is an anticholinergic not an anticholinergic?

Except this is not likely to be the full story. A team at Scripps Research Institute a little over a year ago reported that benztropine had some extraordinarily interesting properties – nothing to do with its anticholinergic actions.

They were studying multiple sclerosis. This is the disease that medical students find most confronting – the one they hope they will never get. It’s an horrific and degrading destruction of nerve cells that strips away dignity slowly over years, confining its victims to wheelchairs and worse.

The problem is that some kind of inflammatory process attacks and destroys the protective myelin covering around nerves. Most treatments aim at suppressing this inflammation. The latest treatments are high cost monoclonal antibodies that come not only with a price tag of tens of thousands of dollars per year but also a high cost in terms of lethal side effects.

But another aspect of MS is that something goes wrong with the normal repair mechanisms. When myelin breaks down in the rest of us, it is usually repaired by oligodendrocyte cells. But in MS this group of cells are not present or doesn’t swing into action.

Taking a different approach to everyone else, the Scripps team screened banks of old drugs to see if anything has an effect on oligodendrocytes and to their surprise found that benztropine did. Tested in animal models of MS, benztropine reversed the defects found in MS and drastically reduced the amount of anti-inflammatories needed. No other anticholinergic does this – so this is nothing to do with benztropine’s anticholinergic action.

The disappearance of Cogentin

Given this, it’s perhaps not surprising to find that around the time this research was first heard of Merck removed Cogentin from almost all markets – even China. The suspicion has to be they and others spotted a fortune to be made by introducing a variation on Cogentin and a fortune to be lost if the sales of Monoclonal Antibodies dropped.

Some forms of benztropine are however still on the US market. The Land of the Free and the Home of the Brave may also be the House of Hope.

What we need to find out is whether patients taking benztropine are less likely to get MS, whether patients with MS who go on benztropine have noticed any difference in their MS and whether this treatment is useful for anything else.

One of the surprising aspects of all this though is that its apparently not hot news in American MS circles. It may be the fact that the studies reported so far have been in animals – but in fact benztropine is pretty safe as these things go. And its available – in the US. I have to say if I had MS I would begin taking it in the morning.

And if I had a relative or friend outside the US with MS, I’d want to get benztropine to them. But it’s not clear how this can be done. Medicines put in the post are liable to be confiscated in the absence of a prescription. So another question is whether there is a legitimate way to get a medicine like this from the US to someone living elsewhere.

Input needed

We need:

• comments from anyone with MS who is using benztropine and figures its making a difference to their MS
• comments from anyone who is using benztropine and figures its making a difference to something.
• comments from anyone outside the US whose benztropine was stopped and finds they have developed new complaints since it was replaced by another anticholinergic.
• comments from anyone who knows the inside story on benztropine’s removal
• comments on how to get benztropine legitimately to people living outside the US

There is a real chance for someone here to win a Nobel Prize, get to take a use patent out on an old drug or just save someone they love or others from an awful fate.