Patent filing for the use of nitric oxide with or without B-cell depletion in CFS

[snowathlete]

http://link.springer.com/article/10.1007/BF01991860?no-access=true

Chronic alcohol exposure, yes. Because, and I have not read the full paper, it seems that tissue damage might result in more NO. This argument might extend to any damage or poison though.

Seems accute exposure has implications also. I get significant reactions from small amounts of alcohol.:
Ethanol metabolism and effects: nitric oxide and its interaction.
EDIT: GREAT MINDS...

 

[SaraEngland]

@Jonathan Edwards, what is your take on all of this? You have probably seen it before, but it is always interesting to hear what you have to say about it.

@alex3619, You think glyceryl trinitrate are safer than the L-Arginine and L-Citrulline combo? Looks like that combo have been used frequently both in studies and for muscle builders

Btw, I get much better from alcohol. One bottle of wine++ makes me able to walk and stand on my feet. The lactic acid feeling almost vanishes.

 

[Jonathan Edwards]

@Jonathan Edwards, what is your take on all of this? You have probably seen it before, but it is always interesting to hear what you have to say about it.

@alex3619, You think glyceryl trinitrate are safer than the L-Arginine and L-Citrulline combo? Looks like that combo have been used frequently both in studies and for muscle builders

Btw, I get much better from alcohol. One bottle of wine++ makes me able to walk and stand on my feet. The lactic acid feeling almost vanishes.

I have always found it difficult to get my head around NO metabolism. Dr Pall has published a few hypothesis papers but hardly any data (one very brief paper) as far as i can see. I doubt he has any solid evidence for his ideas. Dr Fluge and Dr Mella have noted CFS/ME patients reporting benefit with traditional nitrate based drugs but with rapid loss of effect. I think they are starting pragmatically from this observation and trying to explore NO related drugs that might produce continuing effects. I think they would still think of this as speculative exploration that might not stand up to formal studies.

 

[PDXhausted]

Interferon gamma induces NO production via macrophages, is that correct?

 

[Kati]

@Jonathan Edwards could you please explain why drs apply for patents? i just quite understand

 

[deleder2k]

I don't fully understand why, but I know Øystein Fluge and Olav Mella were obliged to do so. It was introduced as a rule by the Regional Health Authority a few years ago if I am not mistaken.

The company which helps them out is called BTO.

Bergen Teknologioverføring AS (BTO) is the technology transfer office in Bergen, supporting ten research institutions in commercialization and technology transfer. Together these institutions employ about 4000 researchers and have a research base of more than 4MrdNOK (billions). Researchers, faculty and students from these institutions provide BTO with up to 100 new innovative ideas and technologies each year, from a broad range of exciting projects. Since the founding in December 2004, BTO has been involved in over 100 commercialisations. BTO’s goal is to help researchers commercialise their research results to ensure that knowledge and inventions benefit individuals, society and industry.

http://bergento.no/about-bto/

 

[Jonathan Edwards]

@Jonathan Edwards could you please explain why drs apply for patents? i just quite understand

They hope to make some money I guess. It is also a way to get funds for a university department so that one can do research.

 

[Jonathan Edwards]

They hope to make some money I guess. It is also a way to get funds for a university department so that one can do research.

From what deleder2k says it sounds as if it is institution policy to patent any research ideas patentable. If everyone else is doing that it makes sense to do the same. I think it is a pity, but it may mean that money comes back to hospitals and universities rather than just going to drug company shareholders.

 

[deleder2k]

http://worldwide.espacenet.com/sear...e&compact=false&DB=EPODOC&query=oystein+fluge

Here are some other patent applications by Olav Mella and Øystein Fluge.

 

[adreno]

Jay Goldstein described and used this years ago. Nothing new here, really.

NO dysfunction is also hypothesized as a mechanism of low flow POTS.

 

[ahmo]

getting rid of peroxynitrite through antioxidants relies on indirect effects. It might work, but I am not sure its ever been clearly demonstrated.

I can assure you it's working for me.

 

[deleder2k]

Jay Goldstein described and used this years ago. Nothing new here, really.

NO dysfunction is also hypothesized as a mechanism of low flow POTS.

They do FMD tests on subjects in the third phase of the Rituximab study. After they have measured FMD, they give the patient nitroglycerin and re-measure FMD. They are also looking at how FMD correlates with the level of ME severity. We need some more research done on this before it can become a viable treatment option.

 

[nandixon]

Jay Goldstein described and used this years ago. Nothing new here, really.

Yes, the patent application needs to be amended to add/disclose the "prior art" of Goldstein's earlier work, and claims numbers 1-7 in the application that refer to the use of a nitric oxide donor (without a B-cell depleting agent, i.e., rituximab) will have to be stricken for any actual patent to have a chance at issuing.

In other words, because of Goldstein they only have a chance at patenting some combination of a nitric oxide donor together with a B-cell depleter.

EDIT: For more on Dr. Goldstein's earlier work, see this thread:

Dr Jay Goldstein's Instant Remission ME/CFS Treatments

 

[Kati]

They do FMD tests on subjects in the third phase of the Rituximab study. After they have measured FMD, they give the patient nitroglycerin and re-measure FMD. They are also looking at how FMD correlates with the level of ME severity. We need some more research done on this before it can become a viable treatment option.

What is FMD again?

 

[deleder2k]

I am not the right person to answer that

I think this one is good in explaining it: http://spo.escardio.org/eslides/view.aspx?eevtid=40&fp=1939

 

[Sidereal]

Jay Goldstein described and used this years ago. Nothing new here, really.

NO dysfunction is also hypothesized as a mechanism of low flow POTS.

It would be nice if new investigators coming into this field bothered to read the previous literature and acknowledged the contributions of those who came before them.

 

[alex3619]

I can assure you it's working for me.

I was referring to raising NO. It does work to counter peroxynitrite and deal with oxidative stress.

 

[alex3619]

Dr Pall has published a few hypothesis papers but hardly any data (one very brief paper) as far as i can see. I doubt he has any solid evidence for his ideas.

I am not up to date on the publications, but last I looked into this every single part of his model is valid, and referenced, though when applied to other similar syndromes there are holes. However this does not make the model necessarily accurate nor complete. In other words, its a valid hypothetical model, but has to be taken further to be demonstrated and tested.

You can assemble a lot of models by using established biochemistry, where each part is accurate. That does not mean the model hangs together. For example, there could be a missing piece, one not taken into account, and it might not have been discovered yet. Or the relative importance of some of the pieces may be so minor that it makes the model moot. Or the way the dynamics of all the parts work together is not captured in the model.

Last I checked there was one small clinical trial of his theory, but not for ME. It showed the therapies helped. Application of such therapies does not prove the model. It proves the therapies. It has to go much further to prove the model.

 

[alex3619]

@alex3619, You think glyceryl trinitrate are safer than the L-Arginine and L-Citrulline combo? Looks like that combo have been used frequently both in studies and for muscle builders

First, the average body builder does not have problems with continual herpes virus infections. Second, the mechanism that creates NO from arginine is one of the things that is potentially problematic. If that mechanism is broken then arginine could drive the illness not the solution. In other words, it could drive peroxynitrite. We need some research to find out.

 

[alex3619]

Could it be that dangerous?

It runs the risk of driving any latent herpes infections. It also might drive the pathological mechanism if the problem is in nitric oxide synthesis itself. I think NO donors bypass these risks. Why take the risk? Of course once we identify the mechanisms we will know more and it might even turn out that arginine is the best option.