Biovista and CAA identify candidate drug for repurposing

[taniaaust1]

"Neuroleptics are psychiatric medications that are used to treat the symptoms of
certain types of mental illnesses, including bipolar disorder "

A list of neuroleptics http://en.wikipedia.org/wiki/Antipsychotic
...................

Some neuroleptics too thou I think are are used to treat epilepsy and seizure disorders... in my case I probably could of done with that kind of drug maybe? (dont know if they help us) when my ME was very neurological in its presentation.

A doctor did put me once on a anti-seizure/antipsychotic drug..but he did at a time I didnt have the shaking and seizure like incidents going on, I do know from that thou it didnt help any of my other symptoms. This doctor was a jerk, he told me he was giving me an epileptic drug when I wasnt even having shaking, tremors and stuff at that time and try to pass the drug off to me under that guise, saying it was for that even when I told him I wasnt getting those symptoms. I know thou he just wanted to give it to me as he thought ME/CFS was a psych illness (he told me I wasnt to look up online what that drug was for.. and the drug just made me quite ill and even worst functional).

Why am I doubting thou that they are finding drugs for neurological ME? When I see the term "neuroleptic" it just makes me think that they've probably just gone from looking at SSRIs for us into psych drugs instead?

One issue thou with these drugs is they seem to be rather toxic and some of these drugs can cause permanent damage in the body.
.............

Im going to take a guess that one of the drugs is going to be gabapentin (Neurontin) a.. but I wouldnt be surprised is its Topiramate (I think thats a neuroleptic and it scored quite high as being positive on that precription drugs being used in ME survey at the other site, only 1 out of the 8 who tried it finding it wasnt helpful..so maybe that would be a good one for many of us?).

I hope it isnt going to be - olanzapine (zyprexa) (another drug a different doctor put me on once, that drug sucks causes a complete wipeout, hard to function state in me).

 

[Carts1]

I am very interested to know whether Cort has some inside knowledge on the nature of the two candidate drugs as twice on his Health Rising blog he has mentioned that they are serotonin affecting.

 

[Nielk]

Maybe they will try a CNS stimulant in the morning and a CNS depressant at night. This will insure that we are constantly drugged up?

 

[Sing]

Those of us who have "been around the block" may try these drugs but stop them quickly if they don't help or cause worse symptoms, but those who are newly diagnosed are apt to be more naive. Having a large patient forum like this is going to be very useful to "compare notes".

 

[urbantravels]

Well, it's a dead lock that regardless of what drug/drugs are being proposed, some people won't be able to tolerate the proposed treatment. That's pretty much true of any drug ever in all time, and we are an especially intolerant group. Of DRUGS, I mean. I think you can also guarantee that some people won't be helped by it, even if it turns out to be helpful for enough people that it gets approved. But we must start somewhere. And this is what clinical studies are for - to correct for anecdotal reporting bias, and to find out whether X side effect is rare, common, or somewhere in between - or isn't a "side effect" at all but something with equal prevalence in the control group.

I hope that once we learn what the drug(s) being proposed are, people will stay level-headed about whatever "statement" they think is being made by the particular choice of drugs.

 

[SOC]

Let's not forget that once we have a medication officially designated for us, we will suddenly have a "real" disease. Remember - not so long ago - when fibromyalgia was an imaginary illness of bored neurotic women? It's got to be some help, in a silly illogical, but surprisingly useful way. Nothing in our physical condition will change, but suddenly our GPs will consider us "real" sick people because they have something to prescribe.

I'm not expecting any huge step forward in the treatment realm with this, but patients who are lacking knowledge or access to specialists will get something. It's a start.

 

[urbantravels]

I agree, SOC. Pharma companies are very big on "educating doctors" about medical conditions when they've got something to sell for said condition. Sometimes this leads to overprescribing shenanigans, as everybody knows.

But here's a disease where doctors really ARE profoundly un-knowledgeable and also believe that there's nothing to be learned. Sure, there have been some outreach efforts but their reach is extremely limited. Now send out an army of sales reps. Have you met pharma sales reps? They're NUTS. They're very, very good at pushing a foot into closed doors. And it's in their interest to emphasize to the doctor, at some length, how serious the disease is.

 

[WillowJ]

and likely same pharma companies were at FDA workshop, where they heard about how serious the disease is. more such workshops to come.

 

[Snow Leopard]

I'm willing to bet that neuroleptics will do nothing for us, but we still need to do the trials to find out. At the very least so we can rule out this line of reasoning...

 

[SOC]

Why is it when I look up "neuroleptic" I get "an antipsychotic drug"? Even if there is an alternative use to these meds, this just doesn't sound good. Please tell me I'm missing something.

 

[Valentijn]

Why is it when I look up "neuroleptic" I get "an antipsychotic drug"? Even if there is an alternative use to these meds, this just doesn't sound good. Please tell me I'm missing something.

It seems that the symptoms such a treatment might help with are rather limited - hard to imagine how they might help better than some simpler and less risky alternatives.

Practicing your psychotic face?

 

[urbantravels]

Now mind you, the mention of neuroleptics in the slide does not necessarily mean that actual neuroleptics are included in the drugs under consideration. The comparison of the three different classes of drugs may just be there to illustrate a point about brain chemistry and modes of action of different drugs.

Can anyone tell me where to find all of the slides? Pecking this one slide to death may also be misleading without some more context. Is there archived video of the meeting available yet? A transcript?

 

[SOC]

Now mind you, the mention of neuroleptics in the slide does not necessarily mean that actual neuroleptics are included in the drugs under consideration. The comparison of the three different classes of drugs may just be there to illustrate a point about brain chemistry and modes of action of different drugs.

Ah, that makes a lot more sense than anything I was thinking.

 

[jspotila]

Can anyone tell me where to find all of the slides? Pecking this one slide to death may also be misleading without some more context. Is there archived video of the meeting available yet? A transcript?

All the meeting resources are here: http://www.fda.gov/Drugs/NewsEvents/ucm319188.htm

Slides Day 1: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM352775.pdf
Slides Day 2: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM353570.pdf
Transcript Day 1: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM354951.pdf
Transcript Day 2: http://www.fda.gov/downloads/Drugs/NewsEvents/UCM355406.pdf

 

[urbantravels]

Thanks JS! I knew if I kept asking plaintively enough someone would come along eventually

 

[urbantravels]

WOW, interesting. (This was one of the many FDA meeting segments I was not able to watch live, so this is the first time I'm seeing this)

If you want to look at Dr Vernon's presentation it starts on p. 53 of the Day 2 transcript, and Slide 37 of the Day 2 slides.

They seem to be suggesting here that serotonin-increasing (serotoninergic) drugs may actually be the exact opposite of what you want, that they are more likely to increase fatigue. [That includes most all of the antidepressants that have been thrown at us for years!] The Central Fatigue Hypothesis has to do with ordinary, healthy-people fatigue being mediated by a natural process involving serotonin.

Look at Slide 45. The drugs at the top of the two lists are those with most reported fatigue, at the bottom with the least. There's some names at the bottom that I am NOT familiar with. Before, I was puzzling over the question of what drugs REDUCE serotonin since increasing it seems to be a grand goal of so many medications. It's really hard to Google up good information on such drugs. But at least one at the bottom of Slide 45 - Periactin, generic name
Cyproheptadine - appears to be antiserotonergic. And it's got a little bundle of diverse indications including treatment of serotonin syndrome (aha!) as well as migraine, allergies, PTSD-related nightmares, and as a sedative for schizophrenics! Interesting that blocking serotonin can potentially have such diverse effects.

That's not a smoking gun that THIS is necessarily one of the drugs we're speculating about - but it does suggest to me that the candidates may not be among the ME/CFS usual suspects and we may be looking at a mode of action that's not already familiar in the drugs we currently use.

 

[Desdinova]

So the grand purpose of this is to find likely candidates to treat ME/CFS run trials to validate them. And then get the FDA to approve those already existing drugs previously established in the market place for ME/CFS. Which could help give not just patients but the public perception of this retched illness a boost of creditability? Which definition will they be using? Fukuda?

 

[Bob]

No user9876, a patent is a unique invention. Sufficient change to an invention is enough to qualify for a new patent. Its already been done, though I am struggling to recall the name of the drug (its an antidepressent, used to be called prozac I think). Its now a new wonder drug, but its the same old prozac, just a different formulation. So the idea can be old, but if there is enough modification then its still a new invention. If they own the old patent, and its still in force, then there is no conflict either.

You can bet that injectable rituximab is likely to have a new patent too.

I don't know much about patenting, or drug repurposing, or drug licensing.
But just on the specific point of making a small change to a drug so that it can have a fresh patent, apparently this is known as "evergreening"...
Alex, I think you may be thinking of Citalopram and the successor is Escitalopram.
Details, here if anyone is interested:
http://en.wikipedia.org/wiki/Escitalopram#History

 

[Bob]

This is from the FDA webcast of Dr. Vernon speaking about the two drugs that are being repurposed.

[Edit: I hadn't done all my homework before writing this - I forgot that the transcript and slides were available.]

Pure speculation (and amateur science):

So it seems that they are looking at the neurotransmitter systems, or they wouldn't mention the antidepressant drugs or antipsychotic drugs, or serotonin or noradrenaline.
And, when looking at the neurotransmitter system, maybe they asked themselves what is the exact biological process that leads to some psychiatric drugs causing fatigue. (And if we can think about this process, maybe we can find drugs that have the opposite effect.) So maybe they asked themselves if there any similar drugs which have opposite effects to the ones that cause fatigue, and if any similar drugs have an activating effect, rather than a fatiguing effect?

But I don't totally understand the logic of the process myself, unless they started from the position that 'fatigue' is caused by a brain (psychiatric) problem, or that the symptom of fatigue can be modulated via the brain.

(Some anti-psychotics, such as Amisulpride, are said to be effective anti-depressants, so maybe they think that this sort of approach would be helpful.)

As far as I can see, 'neuroleptic' is an outdated synonym for 'anti-psychotic', but if used purposely the name could indicate the older types of anti-psychotics (known as 'typical', and 'first generation') which had severe tranquilising side-effects:
http://medical-dictionary.thefreedictionary.com/neuroleptic

Perhaps they used the word purposely, because the earlier anti-psychotics worked more on the dopamine pathways, but the later anti-psychotics work on the dopamine and serotonergic pathways, although they tend to work on serotonergic pathways in a different (opposite) way to SSRI's (Prozac etc.) So I imagine 'neuroleptic' has just been used as a synonym for 'anti-psychotic'.

From their text, in the above slide, it seems that they definitely are not interested in investigating any anti-depressants that work on serotonin or noradrenaline.
And their text, is suggestive that they maybe looking at drugs which work on the dopamine pathways, or that have an opposite effect on the serotonergic pathways to the SSRIs (Prozac etc.)

I've had a look at Olanzapine, one of the newer anti-psychotic drugs, with a lower side effect profile (although still a heavy-duty drug, with potentially dangerous side-effects)...

Whereas Prozac is a serotonin reuptake inhibitor, Olanzapine is a serotine and dopamine 'antagonist' and 'inverse agonist'. So in a way, it has the opposite serotinergic effect than that of Prozac. (A reuptake inhibitor stops a neurotransmitter from being re-absorbed into cells, after release by the cell into the synapse, and so increases the neurotransmitter's levels and effect. An antagonist, blocks a receptor, so usually decreases that receptor's neurotransmitter effects. An inverse agonist binds to a receptor and also lowers its neurotransmitter activity.)

So, in very simplistic terms, Olanzapine has almost the opposite effect of the SSRIs, in terms of increasing or decreasing the levels of a neurotransmitter that it targets.

Olanzapine also has an effect on a variety of other receptors, including adrenergic and histamine:
http://en.wikipedia.org/wiki/Olanzapine#Pharmacology

But anti-psychotics have a huge side-effect profile, including tranquilising effects.

I'm worried that the drug re-purposing effort might not have had enough insight into ME, and might have just thought that it's a simple fatiguing illness. (So let's look at the brain and drugs that affect fatigue.) But what they may not take into account is that if symptoms are hidden in the short-term (simply plastered over), then this might increase the risk from post-exertional malaise, and might lead to severe long-term adverse effects on the illness.

I'm also concerned that it was too easy for them to look at ME in terms of it being an illness that can be modulated via the brain. This may lead them in the wrong research directions, if the cause of the fatigue is not related to neurotransmitters, but it could also be dangerous, as they would be neglecting the cause and the degenerative multi-systemic symptoms.

 

[Bob]

WOW, interesting. (This was one of the many FDA meeting segments I was not able to watch live, so this is the first time I'm seeing this)

If you want to look at Dr Vernon's presentation it starts on p. 53 of the Day 2 transcript, and Slide 37 of the Day 2 slides.

They seem to be suggesting here that serotonin-increasing (serotoninergic) drugs may actually be the exact opposite of what you want, that they are more likely to increase fatigue. [That includes most all of the antidepressants that have been thrown at us for years!] The Central Fatigue Hypothesis has to do with ordinary, healthy-people fatigue being mediated by a natural process involving serotonin.

Look at Slide 45. The drugs at the top of the two lists are those with most reported fatigue, at the bottom with the least. There's some names at the bottom that I am NOT familiar with. Before, I was puzzling over the question of what drugs REDUCE serotonin since increasing it seems to be a grand goal of so many medications. It's really hard to Google up good information on such drugs. But at least one at the bottom of Slide 45 - Periactin, generic name
Cyproheptadine - appears to be antiserotonergic. And it's got a little bundle of diverse indications including treatment of serotonin syndrome (aha!) as well as migraine, allergies, PTSD-related nightmares, and as a sedative for schizophrenics! Interesting that blocking serotonin can potentially have such diverse effects.

That's not a smoking gun that THIS is necessarily one of the drugs we're speculating about - but it does suggest to me that the candidates may not be among the ME/CFS usual suspects and we may be looking at a mode of action that's not already familiar in the drugs we currently use.

I wish I'd read your post, and looked at the slides, before I posted my previous post!
Very interesting.
(I haven't seen the videos or slides yet.)

Thanks for these helpful titbits:

> "The Central Fatigue Hypothesis has to do with ordinary, healthy-people fatigue being mediated by a natural process involving serotonin."

> "Look at Slide 45. The drugs at the top of the two lists are those with most reported fatigue, at the bottom with the least."

> "But at least one at the bottom of Slide 45 - Periactin, generic name Cyproheptadine - appears to be antiserotonergic. And it's got a little bundle of diverse indications including treatment of serotonin syndrome (aha!)"