If only we knew a time frame

[perrier]

I

Seems like some possible good news end of this summer.
http://bit.ly/2HxCxRb

I listened to the video again. And I am wondering, how would one unblock a circuit? Dr Davis says that there are many drugs out there. How would unblocking work?

 

[alex3619]

I

I listened to the video again. And I am wondering, how would one unblock a circuit? Dr Davis says that there are many drugs out there. How would unblocking work?

This is far too general a question to have a good answer. The reply is going to be some version of "it depends", or so general its almost meaningless. In biochemical blocks there will be some failure in an enzyme or transporter, or some failure in regulation, which typically means a failure in an enzyme or transporter. Now in a trap situation there will be multiple effects driving each other.

All these effects might have to be identified. Then you treat each one, at the same time. For an enzyme you might use an activator or deactivator drug, or a drug targeting an activating or deactivating process. You might also supply additional enzyme cofactors, often a B vitamin. A transporter is trickier, and it depends on why and how the transporter is defective. However I think a lot of the time the story will be similar to that of an enzyme.

By a circuit I think Ron means either a circular causal pathway, or a specific molecular switch that is basically on or off, though its probably more like a dimmer switch. How that switch works will give you clues on how to treat it. The big risk occurs if its less a feedback or feedforward loop than its a spaghetti tangle of loops. Those might be hard to figure out, and require a lot of research.

I think it much more likely to be some kinds of feefback loops, rather than feedforward, as I would expect to see rapidly progressing pathology as a risk in feedforward loops. ME pathology seems to mostly be about have a set state, and that implies some kind of feedback effect.

The way existing drugs would be initially tested might be like this. Using the nanoneedle test that identifies a probable problem in ME cells, you create a testbed. Many samples on a tray, many nanoneedles. Then for each column or row you add a specific drug, probably at a high dose initially. If you see an improvement it can then go to the next phase of testing. If not you move to the next drug. Thousands of drugs might be tested this way rather quickly, giving us a short list of possible drugs.

Further testing of candidate drugs might however take more time, effort and resources. Eventually some form of clinical trials might be necessary, though for already approved drugs they could be used off label before such trials are completed.

Its only when we have more science published that we can begin to really look at this.

 

[perrier]

This is far too general a question to have a good answer. The reply is going to be some version of "it depends", or so general its almost meaningless. In biochemical blocks there will be some failure in an enzyme or transporter, or some failure in regulation, which typically means a failure in an enzyme or transporter. Now in a trap situation there will be multiple effects driving each other.

All these effects might have to be identified. Then you treat each one, at the same time. For an enzyme you might use an activator or deactivator drug, or a drug targeting an activating or deactivating process. You might also supply additional enzyme cofactors, often a B vitamin. A transporter is trickier, and it depends on why and how the transporter is defective. However I think a lot of the time the story will be similar to that of an enzyme.

By a circuit I think Ron means either a circular causal pathway, or a specific molecular switch that is basically on or off, though its probably more like a dimmer switch. How that switch works will give you clues on how to treat it. The big risk occurs if its less a feedback or feedforward loop than its a spaghetti tangle of loops. Those might be hard to figure out, and require a lot of research.

I think it much more likely to be some kinds of feeback loops, rather than feedforward, as I would expect to see rapidly progressing pathology as a risk in feedforward loops. ME pathology seems to mostly be about have a set state, and that implies some kind of feedback effect.

The way existing drugs would be initially tested might be like this. Using the nanoneedle test that identifies a probable problem in ME cells, you create a testbed. Many samples on a tray, many nanoneedles. Then for each column or row you add a specific drug, probably at a high dose initially. If you see an improvement it can then go to the next phase of testing. If not you move to the next drug. Thousands of drugs might be tested this way rather



quickly, giving us a short list of possible drugs.

Further testing of candidate drugs might however take more time, effort and resources. Eventually some form of clinical trials might be necessary, though for already approved drugs they could be used off label before such trials are completed.

Its only when we have more science published that we can begin to really look at this.

Dear Alex
Thank you very much, now I am getting a bit of an idea. Thank you. However, when you say "set state," I'm again wondering: some folks, are stable, others improve, and others deteriorate with time. Yes, it is the same problem at root.

Dr Davis also said there was a problem with lipids. Our family member had lipids injected into her veins at a clinic in Switzerland, because they saw a serious problem with lipids, but unfortunately, this treatment didn't alter anything.

 

[Pink]

Just want to adress the part about legitimacy (@Learner1 touched on it in his post re cancer). My husband had cancer and there were so many ppl in our community who offered to help, bring dinners, rides to Drs, his family pitched in, there are so many organizations to call for help etc.
I have been sick for years, no one believes or acknowledges I'm sick. Not family, not neighbors, not community.
I was denied any help for myself from the community, but judged for the paid help I have.
The combination of never ending illness , with no clear end in sight, and denials of my situation have taken a huge toll on me.

 

[alex3619]

Thank you very much, now I am getting a bit of an idea. Thank you. However, when you say "set state," I'm again wondering: some folks, are stable, others improve, and others deteriorate with time. Yes, it is the same problem at root.

The set point would be dynamic, and under the influence of things. Its a set point in that it resists change, not that it is absolutely immovable. Indeed a cure would be about moving the set point back into the healthy range.

With lipids it really depends on what is found. Its so general its a bit like saying its a problem with stuff, though not quite that bad.

I first encountered lipid issues in ME in 1993. Indeed that was the year I tried high dose omega-3 oils to try to help things. It kind of worked a tiny bit, but the effect faded over time.

 

[alex3619]

I think I was being simplistic. If e.g. Dr. Phair (OMF) turns up something (e.g. a blockage in a metabolic pathway) then you may end up with a mass spectrometry diagnostic test. At that stage the testing may use a less sensitive mass spectrometry i.e.rather than metabolomics mass spectrometry currently being used by Dr. Robert Naviaux (OMF) etc.

I think they are hoping to find a minimal set of characteristic changes. They might.

 

[perrier]

Just want to adress the part about legitimacy (@Learner1 touched on it in his post re cancer). My husband had cancer and there were so many ppl in our community who offered to help, bring dinners, rides to Drs, his family pitched in, there are so many organizations to call for help etc.
I have been sick for years, no one believes or acknowledges I'm sick. Not family, not neighbors, not community.
I was denied any help for myself from the community, but judged for the paid help I have.
The combination of never ending illness , with no clear end in sight, and denials of my situation have taken a huge toll on me.

Dear Pink
I would venture to say your experience is replicated thousands of times by ME sufferers all over the world. It is so cruel, so vicious, that I haven't words enough to describe all this. In addition, the illness itself is quite like an abuser, for one never knows even hour to hour what horrid symptom will fell the sufferer. And then on top of that there is social and medical abuse you describe. It is a horror, so painful, so dreadful. I just pray all day that the researchers come up with something very soon.

 

[alex3619]

We have a high suicide rate in ME, and a high attempted suicide rate. The suffering from the disease is in the context of societal, medical and familial abuse and neglect. The wonder is that the suicide rate is not much higher. One of the ironies about the abuse from psychology and psychiatry is that we might well benefit from proper support, but its often the worst of the abuse we get instead.

If that social abuse were to change it would make waiting for a real cure that much easier to cope with. If instead we get a cure first then we can tell abusers where to go.

 

[FMMM1]

We have a high suicide rate in ME, and a high attempted suicide rate. The suffering from the disease is in the context of societal, medical and familial abuse and neglect. The wonder is that the suicide rate is not much higher. One of the ironies about the abuse from psychology and psychiatry is that we might well benefit from proper support, but its often the worst of the abuse we get instead.

If that social abuse were to change it would make waiting for a real cure that much easier to cope with. If instead we get a cure first then we can tell abusers where to go.

Hi there are some article on this paper: Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. I was interested in your views.

I was wondering if this was the great unifying theory/missing link to the puzzle of ME/CFS.

Also, is this a potential way to diagnose ME/CFS? If this is then it might possibly helppeople to get the support they need since they will be viewed as having a demonstrable illness.

 

[Wishful]

I had strong suicidal impulses for a while. They were caused by unusual sensitivity to niacin, which seemed to be caused by the ME/CFS. I did get sent to a psychiatrist (this was before I knew it was ME/CFS), and he said it didn't seem to be clinical depression, but prescribed antidepressants anyway. Do psychiatrists ever do anything other than prescribe antidepressants? When the drugs didn't do anything except make me dizzy, he said he couldn't do anything else for me. I was rather shocked that the professional response to a suicidal patient was 'Sorry, can't help you. Bye.' I went to a mental health clinic some time later, and had basically the same response, without antidepressants (maybe they weren't able to write prescriptions). The suicide hotline also gave me the 'Sorry, can't help you.' response. My guess is that all the suicide prevention services are set up to only help a limited set of suicide causes (clinical depression, relationship failures, etc). ME/CFS patients need not apply.

 

[alex3619]

Also, is this a potential way to diagnose ME/CFS? If this is then it might possibly helppeople to get the support they need since they will be viewed as having a demonstrable illness.

I just found out that here, under the new National Disability Insurance Scheme, at least one person was told she was not going to be helped as she had a medical condition, not a disability.

 

[FMMM1]

I just found out that here, under the new National Disability Insurance Scheme, at least one person was told she was not going to be helped as she had a medical condition, not a disability.

Surreal.

 

[Jackb23]

All we can do right now is hold on and do our best to advocate on all of our behalf’s. But man is it a gut wrenching emotion to think of holding our families and loved ones in our arms when our daily torture and suffering diminishes so we can find a newfound peace.