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Patent for "new" meds used to treat ME debilitating fatigue

Valentijn

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Is there any promise to the patented drugs in treating our fatigue.
They aren't patenting the drug, but rather the idea of using it as a treatment. These types of patents are completely 100% meaningless - it's no indication at all that there might be an effective or even rational treatment behind it. Just someone having a random thought and hoping they'll get lucky some day.
 

valentinelynx

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I took a look at the patent, as best as I could at present (not able to process it too well), and it is a use patent (as described by @Valentijn) for "dopamine stabilizing agents" (I was able to find an article about one of them, called "(−)-OSU6162", which is an experimental drug) in combination with just about any antidepressant you can think of.

The "inventors" found some beneficial effect (sorry I can't figure out what they were looking at right now—some scales were used) when the "dopamine stabilizers" were used in combination with an antidepressant, but zero response with the dopamine stabilizers alone. From the little I could process, however, it appeared that the effects they found were either minimal or measured over much to short a period of time to be clinically useful (2 weeks?!).

"Dopamine stabilizers" as a class have been used generally as "atypical" anti-psychotics, e.g. Ability (aripiprazole). Maybe there is some there is in this stuff, but it looks pretty preliminary to me. Sorry I'm not up to a more cogent analysis at present. It doesn't make me want to jump up and try this drug combo, however.
 

Navid

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I took a look at the patent, as best as I could at present (not able to process it too well), and it is a use patent (as described by @Valentijn) for "dopamine stabilizing agents" (I was able to find an article about one of them, called "(−)-OSU6162", which is an experimental drug) in combination with just about any antidepressant you can think of.

The "inventors" found some beneficial effect (sorry I can't figure out what they were looking at right now—some scales were used) when the "dopamine stabilizers" were used in combination with an antidepressant, but zero response with the dopamine stabilizers alone. From the little I could process, however, it appeared that the effects they found were either minimal or measured over much to short a period of time to be clinically useful (2 weeks?!).

"Dopamine stabilizers" as a class have been used generally as "atypical" anti-psychotics, e.g. Ability (aripiprazole). Maybe there is some there is in this stuff, but it looks pretty preliminary to me. Sorry I'm not up to a more cogent analysis at present. It doesn't make me want to jump up and try this drug combo, however.

V: Thanks for the detailed response and the time and energy it took you to provide, I appreciate it. Bummer, as usual nothing to look forward to.

Thanks to all others who responded : )
 

user9876

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They aren't patenting the drug, but rather the idea of using it as a treatment. These types of patents are completely 100% meaningless - it's no indication at all that there might be an effective or even rational treatment behind it. Just someone having a random thought and hoping they'll get lucky some day.
Generally patents are quite cheap to file but get more expensive as they age in terms of renewal fees. So I suspect it won't be maintained.

They may also run into prior art issues as anti-depressents have been used to treat ME and they need to demonstrate a non-obvious inventive step. Anti-depressents have also been successfully used for treating chronic pain - I think I have even seen the suggestion that some are better at that than they are at treating depression.
 

user9876

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Patent trolling, sigh. There should be a need to demonstrate that claims are actually viable before patents are accepted.
You have to convince the patent office that the invention is viable hence no one has yet managed to patent a perpetual motion device. Also it needs to be a new idea and not obvious to someone who knows the state of the art.

A patent gets published prior sometime after being filed and that can be before being granted.
 
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You have to convince the patent office that the invention is viable hence no one has yet managed to patent a perpetual motion device. Also it needs to be a new idea and not obvious to someone who knows the state of the art.
Yet some of them get through. There are even websites dedicated to calling out patents of perpetual motion devices, along with patents that are not at all new ideas, but prior art...

Example from Australia:
http://blog.patentology.com.au/2015/04/patenting-perpetual-motion.html
 

user9876

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Yet some of them get through. There are even websites dedicated to calling out patents of perpetual motion devices, along with patents that are not at all new ideas, but prior art...

Example from Australia:
http://blog.patentology.com.au/2015/04/patenting-perpetual-motion.html
I remember perpetual motion machines being given as an example of non-patentable things by a patent lawyer but obviously some slip through. There used to be a tradition that the UK (and I think European) patent offices examined things carefully but the US put a lot less effort into looking at the patent initially and relied on litigation to clear things up. But I was told that around 15-20 years ago and a lot can change in that time.
 

mango

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The Swedish scientist/neuropharmacologist Arvid Carlsson (was awarded the Nobel Prize in Medicine in 2000) has been studying OSU 6162 for some years now. Mainly MS, fibromyalgia and Huntington's, I believe, but also brain fog in for example ME/CFS.

Some very positive things have been said in various discussion groups about the effects of OSU 6162, by some ME-patients (CCC) who took part in one of the recent studies, which was a collaboration with the Swedish ME/FM centre the Gottfries Clinic.

Here are a couple of articles, in Swedish:

Svenskt medel testas mot trötta hjärnor (2014)

https://www.svd.se/svenskt-medel-testas-mot-trotta-hjarnor

Ny behandling mot narkolepsi och hjärntrötthet (2015)
http://sverigesradio.se/sida/artikel.aspx?programid=2151&artikel=6217384

Det här är bara början (paywalled)
http://www.aftonbladet.se/nyheter/article20130205.ab/promo
 
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Hip

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The Swedish scientist/neuropharmacologist Arvid Carlsson (was awarded the Nobel Prize in Medicine in 2000) has been studying OSU 6162 for some years now. Mainly MS, fibromyalgia and Huntington's, I believe, but also brain fog in for example ME/CFS.
And the co-applicant on this patent is Professor Carl-Gerhard Gottfries, inventor of the highly effective Staphylococcus toxoid vaccine treatment for ME/CFS, and head of the Gottfries ME/CFS Clinic in Sweden.



Found this while roaming around the net today:

https://patentscope.wipo.int/search...=&sortOption=&queryString=&tab=PCTDescription

Is it possible for one you "scientists" to determine what drugs they are using here. Is there any promise to the patented drugs in treating our fatigue.
This is an interesting finding, Navid. The short answer to your question is that this intriguing treatment for ME/CFS involves taking a combination of two drugs:
  • A dopamine system stabilizer drug (examples of such drugs are aripiprazole, which is readily available, and the drug OSU6162)
  • An antidepressant (such as an SSRI, SNRI, TCA or MAOI antidepressant drug, or even a herbal antidepressant such as St John's wort).
Dopamine system stabilizer drugs work in a unique way: at low dopamine levels, they stimulate dopamine receptors, whereas at high dopamine levels, these drugs inhibit dopamine receptors. In other words, they amplify "soft" dopamine signals, but turn down the volume on "loud" dopamine signals.

Third generation antipsychotics work by a dopamine system stabilizer mechanism.


In the patent the authors state:
The present inventors have unexpectedly found that the clinical outcome of treatment of disorders characterized by debilitating fatigue is significantly improved by the combination of a dopamine stabilizing agent and an anti-depressive agent.


A clearer pdf version of this patent can be downloaded from here.

On pages 20 to 37 of the pdf patent document, the authors detail some double-blind placebo controlled studies performed at the Gottfries Clinic, using dopamine system stabilizer drug OSU6162, and various antidepressant drugs, to treat ME/CFS patients (patients satisfied both the CDC Fukuda criteria and the International Consensus Criteria for ME/CFS).

I am not very good at reading through large amounts of text, but from what I can work out, when either antidepressant drugs or the dopamine system stabilizer drug OSU6162 were used alone, there was no improvement in ME/CFS symptoms (no difference between the active and placebo controlled groups in the study).

But when OSU6162 was used concomitantly with an antidepressant, there were improvements in ME/CFS symptoms. And this concomitant use is the basis for this invention.

The patent says:
No difference between OSU6162 treated and placebo treated patients on any scale was observed in the groups of patients who were not on antidepressant therapy.

In summary, the above analyses show that OSU6162 was, after one week of treatment, more efficient than placebo in improving symptoms according to the FF- and MFS-scales in patients on stable antidepressant therapy.
In other words, OSU6162 only worked for ME/CFS when taken with an antidepressant.

So these researchers appear to have discovered that a combination of a dopamine stabilizing agent and an antidepressant drug or supplement improves symptoms of ME/CFS.



General Info on Dopamine System Stabilizers

Dopamine system stabilization is a mechanism of action of the latest third generation anti-psychotics such as Abilify (aripiprazole), and Solian (amisulpride). Amisulpride in fact was the original third generation antipsychotic. Ref: 1

Some info on Abilify (aripiprazole):
Aripiprazole's mechanism of action differs from all antipsychotics on the market. All current neuroleptics, both traditional and atypical, create their antipsychotic effect by blocking dopamine D2 receptors--that is, they are D2 antagonists (Figure 1).

Aripiprazole exerts its effect by D2 partial agonism (Figure 2), and this distinction holds promise for stabilizing the dopamine system (Stahl, 2001a). It is important to note that a partial agonist can act as an agonist or an antagonist, depending on the concentration of a specific neurotransmitter (Tamminga, 2002).

Source: Aripiprazole: A Third Generation of Antipsychotics Begins
This Medscape article details dopamine system stabilizers:
These medications, referred to as dopamine system stabilizers and exemplified by the prototype drug aripiprazole, sound magical. They are described as binding to dopamine receptors, particularly D-2 receptors, in such a way that they are neither agonists nor antagonists, but instead magically affect the receptor in just the right way to make the patient better.


My Experience With Dopamine System Stabilizer Drugs

I can vouch for the benefit of very low dose amisulpride or ME/CFS symptoms, as I have been taking this daily for several years.

I have also tried very low dose Abilify, and found it very similar to very low dose amisulpride, except that I found Abilify a bit over-stimulating, an effect that I did not get from amisulpride, so I stuck to amisulpride.

I don't usually take any antidepressant drugs with my very low dose amisulpride, I should add, but I still find amisulpride beneficial for several ME/CFS symptoms.
 
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IreneF

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Atypical antipsychotics are sometimes added to antidepressants to make them more effective. I have no idea whether it actually makes any difference.
 
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I can vouch for the benefit of very low dose amisulpride or ME/CFS symptoms, as I have been taking this daily for several years
I wouldn't be so quick to vouch for a drug like amisulpride just because it works for you. What ME/CFS symptoms are you getting relief from? From reading your posts over the years, you have tried tons of things and seem to take multiple things at once so isn't it difficult to pinpoint where the relief is coming from?


The side-effect profile of anti-psychotics isn't good to start with and could be devastating to a person who is intolerant of meds/chemicals as many with ME are.

Side-effects include:

-Extrapyramidal which can be horrible
-hyperactivity
-insomnia
-nausea
-headache
-anxiety
-vomiting
-hyperprolactinaemia
-weight gain
-constipation
-dry mouth
-blurred vision

These are just the common side-effects. Combine that with the side-effects of an anti-depressant. :eek::eek::eek:

What symptoms would such a combination target -- ME is more that 'debilitating fatigue' as described by the authors. One of the biggest complaints of patients who take anti-psychotics/anti-depressants are the side-effects. Too many psychiatric medications are being used off-label in a manner with little or no research to back up effectiveness etc. Many times these meds are only effective for some people and often for a limited amount of time.

I know low-dose anti-depressants are used in ME and Fibro for sleep issues as are some low-dose anti-psychotics -- meant to be short-term only. Why are they prescribed -- the biggest side-effect is drowsiness/sedation.

Antipsychotic medicines are sometimes used to help relieve long-term pain. There is some research to support this but more is needed.

There is lot of conflicting information out there about the use of combos -- from it's dangerous to it's very helpful.

There is a lot of information about the pros and cons of the combination which was ignored in the patent paper. It also takes 2-4 weeks for these drugs to show any beneficial effect. I don't know what time frame they used. There is a lot of non-compliance to these meds in the beginning because of adverse side-effects and patients don't wait long enough to see any positive effects.

If you read the information in the link, they did not mention side-effects even once. I think it's downright ignorant and dangerous to try to patent a combination of an anti-psychotic/anti-depressants both of which are known to have numerous nasty and prolonged side-effects to a patient population that is known to be quite sensitive to medications as part of their illness. You would think that would be an important consideration. The whole idea seems to ill-conceived and a great money grab --

Additionally, many disorders, in addition to ME/CFS and FM, are characterized by symptoms of debilitating fatigue. Such disorders include mental fatigue, post stroke fatigue, Huntington's disease, Parkinson's disease, multiple sclerosis, narcolepsy, post cancer fatigue, fatigue associated with cancer with or without cytostatic treatment, depression and combinations thereof.

Thus there is a large need for novel therapies and treatments to alleviate fatigue symptoms, such as ME/CFS associated fatigue symptoms and fatigue symptoms associated with other clinical indications, and thus the provision thereof remains a matter of substantial interest within the field.
Fatigue itself is present in most medical conditions to some degree -- what a money maker. Don't know why these clowns think they have an answer.

They would likely only be treating ME via side-effects anyways and many would find themselves with added problems from the combo eg: further meds to treat the side-effects of the combo.

From the paper:

Currently, patients suffering from ME/CFS are treated by cognitive behavioral therapy (CBT) or graded exercise therapy (GET), which have shown moderate effectiveness in multiple randomized controlled trials, however many patients do not make recovery (Rimes KA ef a/ (2005), Occupational Medicine 55(1 ): 32-39;Chambers D
ef a/ (2006)
Glad they did their research -- sarcasm intended. No mention other many of any other treatments currently being used or researched.
 

Hip

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I think it's downright ignorant and dangerous to try to patent a combination of an anti-psychotic/anti-depressants both of which are known to have numerous nasty and prolonged side-effects to a patient population that is known to be quite sensitive to medications as part of their illness.
I think we need a quick review of what a patent is and is not. A patent is not medical advice, a patent is not a guarantee of safety, a patent is not FDA approval of a treatment, and a patent is not an invitation for the general public to try out the invention detailed in the patent.

In pharmacology (or any other field of invention), a patent provides protection for its holder such that if they decide to invest the many millions required to develop a drug treatment, they are then given the opportunity to recoup their investment by means of exclusive rights to sell the product for 20 years. Without a patent, you will usually not get any investment into the development of a drug, because there is no way to recoup the investment. Thus a patent just lays the foundation for further research and development of a drug.

The full safety and efficacy profile of a patented pharmacological treatment would only be determined as part of the research and development process, and the clinical trials.

If anyone came across a new compound that could cure ME/CFS, the worst thing in the world they could do would be not to patent it, because then that compound would likely never receive any funding for research, development and clinical trials.



What ME/CFS symptoms are you getting relief from?
Significant improvements in ME/CFS sound sensitivity (hyperacusis), and mild improvements in fatigue and cognition are the ME/CFS symptoms I find very low dose amisulpride helps. Improvements in ME/CFS fatigue were also found in the small scale study linked to in my amisulpride post.

I also find very low dose amisulpride also helps reduce the ME/CFS information overload on the brain, and reduce the over-sensitivity to the presence of people and the information overload of socializing, so it facilitates easier socializing.

In addition, I find it helps a number of common comorbid symptoms and conditions that my virus triggered, including depression, which is a common comorbidity in ME/CFS anyway.


Side effects of anti-psychotics can be serious, and include the triggering of diabetes or extrapyramidal symptoms like tardive dyskinesia. For this reason, they not used whenever a safer drug will suffice.

However, I am on the very low dose protocol of amisulpride (= 100th of the normal full dose), and in this very low dose protocol, amisulpride works in the opposite way to its full dose regimen. In the very low dose protocol, amisulpride actually boosts the dopaminergic system, whereas in the full dose regimen, amisulpride inhibits the dopaminergic system (which antipsychotics usually do). Amisulpride is in effect a different drug when used at the very low dose protocol.

It is the dopaminergic inhibition caused by anti-psychotics that is linked to triggering the extrapyramidal symptoms; so the fact that in my very low dose amisulpride protocol I get dopaminergic boosting rather than inhibition likely means that this protocol will not be subject to the risks of extrapyramidal symptoms.


In any case, in the patent they do not talk about antipsychotics, but rather dopamine stabilizing agents, a drug class which includes the latest third generation antipsychotics like amisulpride and aripiprazole, but also drugs like pridopidine, which are not classed as antipsychotics.
 

Jesse2233

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But when OSU6162 was used concomitantly with an antidepressant, there were improvements in ME/CFS symptoms. And this concomitant use is the basis for this invention.
Very interesting Hip. Do you believe this treatment offers symptomatic relief or actually targets underlying core brain pathology?
 

Hip

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Very interesting Hip. Do you believe this treatment offers symptomatic relief or actually targets underlying core brain pathology?
It is hard to say, but it could in part work on the core brain pathology, because I have seen some research by Dr Andrew Miller speculating that low dopamine in the brain may be exacerbating neuroinflammation. So by increasing dopamine receptor activation, we may be able to lower brain inflammation, and so in this way target the brain inflammation in ME/CFS.

This paper and this paper also indicate that dopamine D2 receptor activation reduces neuroinflammation.

That possible anti-neuroinflammation effect of dopamine could be one of the reasons why I find very low dose amisulpride helpful, because this very low dose protocol activates the dopamine D2 and D3 receptors.

Another dopamine boosting drug that seems to relieve fatigue in ME/CFS is amantadine, which I have also tried. I prefer very low dose amisulpride though; it feels cleaner and more refined, and kind of more "natural" in the sense that very low dose amisulpride does not feel like a drug.


I did not know that amisulpride is classed as a dopamine stabilizing agent, even though I have been taking this drug at a dose of 12.5 mg daily since 2012! I'd never heard of the concept of dopamine stabilizing agents before I read that patent, and that has been an interesting discovery for me.
 
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wastwater

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Interesting find,another anti psychotic used at low levels sometimes for depression is fluanxol
 
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Interesting thread. I took Venlafaxine and Quetiapine for 4 weeks and had some improvement. I took it because my doc thought my symptoms are psychosomatic. I didn’t know that the improvements could be due to those drugs and i stoped taking them. About 1 week after my ME got significantly worse.

Do you think it would be useful to add an antidepressant to abilify? I’m currently trialing abilify with no success so far. From what I heard, it’s not prescript with antidepressants by Stanford?

@Hip

I might try Venlafaxine and Quetiapine again if abilify doesn’t work.
 

Hip

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Do you think it would be useful to add an antidepressant to abilify?
I don't think antidepressants generally help ME/CFS, although there is a study to show that moclobemide can increase the sense of energy in ME/CFS. And Dr David Bell found amantadine 25 mg to 50 mg twice daily helps reduce fatigue ME/CFS.

If course if you have depression, which many ME/CFS patients do, then some sort of antidepressant treatment might be useful.