Seeing Dr John Chia on Friday, What Questions Should I Ask?

[Hip]

The doctor walked into the room and before me or my husband said ONE word he made a quite negative comment about my doctor who I do hold in high regard. He then gave a monologue on how he was unappreciated and not funded like the location where my doctor worked as if this was some how my fault?!!

Are you sure you are not reading into this something that was not really there? Dr Chia may just have been generally moaning, and perhaps even feeling sorry for himself compared to other better funded ME/CFS doctors.

Jesse encountered the same moans in his visit to Dr Chia, but as far as I can see, Jesse did not take these moans personally. I don't know, I was not there at your appointment, so I can't really comment. But could you be taking it personally, when in fact Dr Chia's comments were just general moans, not directed at anyone?

 

[Hip]

Let's try to estimate... Chia says he's treated 1000 people with Equilibrant, so that would be 300 who have had the level of improvement he states at a 30% basis. If we discount that by half to get rid of any subconscious reporting bias he has, we get 150 people.

Is 150 a reasonable estimate? Say 10% post online, so there should be 15 Equilibrant success stories to find somewhere.

I'm making a lot of assumptions, let me know your thoughts

That 15 figure is a good ballpark estimate I think. And if you say that Dr Klimas is also treating patients with oxymatrine, that's a few more oxymatrine patients.

There would also be the people like me who have never seen Dr Chia, but nevertheless tried oxymatrine after reading about it on ME/CFS forums. People who post a lot on ME/CFS forums are going to be much more likely to detail their oxymatrine experience, because such people are accustomed to reporting their treatment successes and failures online. Whereas those who never post on forums, and then go to a doctor like Chia or Klimas and get an amazing bedbound to back-to-work recovery from oxymatrine, may unfortunately never even think of passing on the information about their great success to the ME/CFS community.

I might set up a poll on this forum, asking about people's experiences with oxymatrine.



I just thought of another question that it would have been good to ask Dr Chia: does oxymatrine only work for (or work better for) enterovirus-associated ME/CFS, or does it work for ME/CFS associated with other infections such as EBV?

Because that's another possible factor in Dr Chia's oxymatrine success rate: possibly Dr Chia may get to see more enterovirus-associated ME/CFS patients, because people know that's his specialty.

 

[Hip]

Unfortunately he didn't say the name, just that it was a series of letters and numbers

Did you manage to get a chance to listen to your recording of your appointment with Dr Chia, and decipher that codename for the new CVB4 antiviral drug from Belgium — the codename that was a series of letters and numbers?

Current codename for anti-enterovirus drugs being developed include:

TTP 8307 — potently inhibits CVB3 and poliovirus by interfering with the synthesis of viral RNA
V-073 / SCH-48973 (pocapavir) — capsid inhibitor for poliovirus, CVB and echovirus
GPC-N114 — RNA polymerase inhibitor, broad-spectrum anti-enterovirus, potent for CVB3 in vitro
Ro 09-0179 — flavone from Agastache rugosa, antiviral for rhinoviruses and CVB
SDZ 35-682 — a capsid-binding agent, potently inhibits several rhinoviruses and EV9
MDL-860 — broad-spectrum anti-picornavirus activity, including CVB3
TBZE-029 — inhibits CVB3, EV9, CVA9 and enterovirus 6

The initial letters of these codenames incidentally refer to the pharmaceutical company who are doing the research and development on a drug (eg SCH = Schering-Plough Pharmaceuticals). See: List of pharmaceutical compound number prefixes - Wikipedia

It would be great to find the codename of this new CVB4 antiviral drug from Belgium, just to check up on its progress, and find out when it will become available for sale.

 

[Jesse2233]

Did you manage to get a chance to listen to your recording of your appointment with Dr Chia, and decipher that codename for the new CVB4 antiviral drug from Belgium — the codename that was a series of letters and numbers?

Current codename for anti-enterovirus drugs being developed include:

TTP 8307 — potently inhibits CVB3 and poliovirus by interfering with the synthesis of viral RNA
V-073 / SCH-48973 (pocapavir) — capsid inhibitor for poliovirus, CVB and echovirus
GPC-N114 — RNA polymerase inhibitor, broad-spectrum anti-enterovirus, potent for CVB3 in vitro
Ro 09-0179 — flavone from Agastache rugosa, antiviral for rhinoviruses and CVB
SDZ 35-682 — a capsid-binding agent, potently inhibits several rhinoviruses and EV9
MDL-860 — broad-spectrum anti-picornavirus activity, including CVB3
TBZE-029 — inhibits CVB3, EV9, CVA9 and enterovirus 6

The initial letters of these codenames incidentally refer to the pharmaceutical company who are doing the research and development on a drug (eg SCH = Schering-Plough Pharmaceuticals). See: List of pharmaceutical compound number prefixes - Wikipedia

It would be great to find the codename of this new CVB4 antiviral drug from Belgium, just to check up on its progress, and find out when it will become available for sale.

Hey Hip, sorry for the delay in getting back to you. I listened but Chia didn't mention the specific drug code, just that it's name was a series of letters and numbers

 

[Hip]

Hey Hip, sorry for the delay in getting back to you. I listened but Chia didn't mention the specific drug code, just that it's name was a series of letters and numbers

Hi Jesse. Thanks very much for trying to find out the name all the same. Much appreciated.

Several days ago another one of Dr Chia's patients kindly PM'ed me about this, and said that this new anti-enterovirus drug was originally developed by the Rega Institute in Brussels, Belgium, and then last year the rights to the drug were bought by a European pharmaceutical company, with the view to putting it through clinical trials.

However, so far, even with this information, I have not been able to find out the name of this anti-enterovirus / anti-picornavirus drug, nor the European pharmaceutical company that bought the rights to this drug.

 

[Jesse2233]

Hi Jesse. Thanks very much for trying to find out the name all the same. Much appreciated.

Several days ago another one of Dr Chia's patients kindly PM'ed me about this, and said that this new anti-enterovirus drug was originally developed by the Rega Institute in Brussels, Belgium, and then last year the rights to the drug were bought by a European pharmaceutical company, with the view to putting it through clinical trials.

However, so far, even with this information, I have not been able to find out the name of this anti-enterovirus / anti-picornavirus drug, nor the European pharmaceutical company that bought the rights to this drug.

Hmm next time I see Dr Chia I will try to get more info as well. I recall you saying that you've corresponded with him in the past about your website. You could try emailing him in the meantime

 

[Hip]

Hmm next time I see Dr Chia I will try to get more info as well. I recall you saying that you've corresponded with him in the past about your website. You could try emailing him in the meantime

I guess I could do, but I kind of don't want to impose on his time, given that I am not even his patient. I'll find the name eventually. There's no rush, in the sense that this drug will not be available anyway for a few years.

I may write to the Rega Institute themselves and enquire. I will also ask Rega if they are aware of the enterovirus connection to ME/CFS, and the possibility that a potent anti-enterovirus compound may be able to effectively treat the 17 million ME/CFS patients worldwide. So few researchers are aware of ME/CFS, let alone aware of its connection to enterovirus, that it is always good to inform them about ME/CFS.

 

[halcyon]

I may write to the Rega Institute themselves and enquire. I will also ask Rega if they are aware of the enterovirus connection to ME/CFS, and the possibility that a potent anti-enterovirus compound may be able to effectively treat the 17 million ME/CFS patients worldwide. So few researchers are aware of ME/CFS, let alone aware of its connection to enterovirus, that it is always good to inform them about ME/CFS.

I believe Dr. Chia went to Rega towards the end of last year and spoke with researchers there, so hopefully they are now aware of the connection.

 

[Hip]

I believe Dr. Chia went to Rega towards the end of last year and spoke with researchers there, so hopefully they are now aware of the connection.

If only other scientists would take an interest in enterovirus research, and also make efforts in bringing this research forward. It seems that it is currently only Dr John Chia that takes any interesting in moving forward with the enterovirus perspective of ME/CFS. (Dr Byron Hyde is of course also very interested in the enterovirus angle of ME/CFS, but I believe he is retired now, as is Dr Peter Behan et al in the UK).

 

[halcyon]

It seems that it is currently only Dr John Chia that takes any interesting in moving forward with the enterovirus perspective of ME/CFS. (Dr Byron Hyde is of course also very interested in the enterovirus angle of ME/CFS, but I believe he is retired now, as is Dr Peter Behan et all in the UK).

Dr. Hyde is definitely still actively seeing patients. He also just recently updated his Nightingale definition, tying the disease much more closely with enteroviruses than he has in the past. This is one of the best modern descriptions of the disease that I've seen. He also presented this at IACFS/ME and to Maureen Hanson's team at Cornell late last year.

 

[Hip]

He also just recently updated his Nightingale definition, tying the disease much more closely with enteroviruses than he has in the past.
...
He also presented this at IACFS/ME and to Maureen Hanson's team at Cornell late last year.

Wow that looks a very interesting read, I shall have a good look at that.

I did not realize that Dr Hyde continues to play an active role in ME/CFS and enterovirus research.

 

[Hope01]

Hi all, after researching the August Europic 2016 meeting on picornaviruses & enteroviruses in Switzerland, http://europic2016.org/wp-content/uploads/2015/07/Programme-Europic-final_web.pdf
I think I have come across the new CVB4 antiviral drug from the Rega Institute in Belgium. This is on pg 139 of the pdf. I highly recommend for those with chronic enterovirus infections to read/at least browse to the relevant topics in this pdf summary of the conference, it is incredibly detailed but it is the most up to date research/information on enteroviruses there is currently in the medical/ research world.

AN ENTEROVIRUS INFECTION MOUSE MODELS TO STUDY ANTIVIRAL THERAPY AND THE POTENTIAL DEVELOPMENT OF RESISTANCE

Els Scheers, Leen Delang, Johan Neyts
KU Leuven – University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy

OBJECTIVES: We report the development of a relevant enterovirus mouse infection model that is ideally suited to (i) assess the antiviral ef cacy of enterovirus inhibitors and (ii) monitor the possible in vivo development of antiviral drug-resistance.

METHODS: SCID mice were infected intraperitoneally (ip) with 105 TCID50 Coxsackievirus B4 (CVB4) and weight loss was monitored as a symptom of disease. CVB4 RNA and infectious particles in serum and organs were quanti ed by means of qRT-PCR and end-point titration respectively. Viral RNA was genotyped by Sanger sequencing.

RESULTS: As of day 3 post infection (dpi), weight loss was observed in infected mice which all had to be euthanized at 5 dpi. High viral RNA titers (~109 genome equivalents (GE)/100mg tissue) were detected in the pancreas. Titers in heart, lung, liver, spleen and brain were ~106-107 GE/100mg tissue. High titers of both viral RNA (109 GE/mL) and infectious particles (106 TCID50/ml) were detected in serum. To explore whether this model can be used to assess the ef cacy of antiviral compounds, the effect of compound A (a proprietary 2C-targeting enterovirus inhibitor) was studied. CVB4-infected mice were treated for either 5 or 12 consecutive days with twice daily (BID) dosing of 20 mg/kg. After stop of treatment, the mice remained healthy until the end of the experiment (60 dpi) and no virus was detectable in serum or pancreas. Next, infected mice were treated with suboptimal regimens: either 20 mg/kg once daily during 15 consecutive days or 20 mg/kg once daily during 20 consecutive days (treatment was initiated at day of infection). The mortality rate of both groups was 40% and the mean day of death 45 ± 12 dpi and 48 ± 10 dpi respectively. The 60% of mice that survived were euthanized at 77 dpi; no virus was detectable in serum or organs indicating that they were cured from infection. To assess whether the (delayed) mortality in the 40% of mice was due to the emergence of drug-resistant variants, viral RNA was isolated from serum, heart and pancreas and the 2C gene was sequenced. Interestingly, in nearly all samples one substitution i.e. 2C_A239T/V was identi ed. This mutation did not result in a reduced sensitivity to the inhibitor as assessed in vitro and in mice that had been inoculated with these variants. Full genome sequencing revealed the presence of additional mutations in the viral genome for which it is being explored whether these, and the 2C_A239T/V, represent mouse adaptive mutations.

CONCLUSIONS: We developed a robust CVB4-infection mouse model to assess the in vivo ef cacy of novel antiviral agents. We demonstrate that a potent antiviral agent is able to cure immunode cient mice from this aggressive enterovirus infection. It was next explored whether suboptimal dosing (that delays but does not prevent mortality of all infected mice) may lead to the selection of drug-resistant variants. For this particular inhibitor, no drug-resistant variants developed. This CVB4/SCID model provides a powerful tool to study population dynamics over time in the presence or absence of antiviral pressure in the infected host.

 

[Hope01]

I noted in your consult @Jesse2233 that Dr Chia reported of 2 potential CVB4 antivirals, I think this study also from the Rega Institute in Belgium maybe the second antiviral he is talking about although it was targeted for CVB3 the compound proved to inhibit CVB1, CVB4, CVB5, CVB6.
http://europic2016.org/wp-content/uploads/2015/07/Programme-Europic-final_web.pdf
pg 140

THE TALE OF HOW AN IN SILICO DESIGNED COXSACKIEVIRUS B3 PROTEASE INHIBITOR TURNED OUT TO BE A CAPSID BINDER WITH A NOVEL MECHANISM INSTEAD

Rana Abdelnabi1, Ajay Kumar Timiri2, Venkatesan Jayaprakash2, Leen Delang3, Johan Neyts3, Pieter Leyssen3
1KU Leuven – University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, 2Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi-835215, Jharkhand, India., 3KU Leuven – University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000 Leuven, Belgium

OBJECTIVES: An in silico molecular docking study on the Coxsackievirus B3 (CVB3) 3C-protease guided the synthesis of a novel benzene sulfonamide derivative (i.e. compound 17) that was shown to inhibit the in vitro replication of CVB3. Our aim was to use virus-cell-based assays to con rm the 3C-protease as a target for the compound and to study the particular characteristics of its antiviral activity.

METHODS: Cell-based antiviral assays (CPE-reduction, virus yield and plaque assays) and molecular biology tools (reverse-engineering, RT-PCR and sequencing).

RESULTS: Compound 17 proved to inhibit the in vitro replication of CVB3 (strain Nancy) as well as of CVB1, CVB4, CVB5 and CVB6 with EC50 values ranging between (0.7-37) μM. Surprisingly, the compound did not show any antiviral activity against CVB2 and other viruses from different enteroviruses groups. In contrast to what is expected for a protease inhibitor, a time-of-drug-addition study pointed out that compound 17 interfered with an early step in the CVB3 replication cycle. A thermo-stability assay provided an additional indication of an interaction between compound 17 and the CVB3 virus particle. This latter mechanism of action was con rmed by the genotyping of independently selected compound 17-resistant CVB3 variants, which all carried mutations in the VP1 gene (F76C, E78G, A98V and D133G). Compared to the wild-type (WT), the reverse-engineered VP1 F76C, E78G, A98V and D133G mutants proved to be 18, 21, 3 and 38-fold less sensitive to the antiviral effect of compound 17, respectively. Interestingly, the mutated VP1 residues are located outside the common drug-binding pocket for capsid binders such as pleconaril. Moreover, the D133 residues of all ve VP1 units are arranged in the form of ion channel at the 5-fold axis. Plaque phenotyping revealed that the VP1 F76C, E78G and D133G mutations resulted in a smaller plaque size than WT.

CONCLUSION: Compound 17, originally designed in silico to inhibit the viral 3C-protease, is a potent inhibitor of CVB3 replication. Surprisingly, study of the mechanism of action revealed that the compound is a capsid binder with an entirely new target on the virus particle. Further experiments are ongoing to explore the precise mechanism by which compound 17 interacts with CVB3 capsid and to develop more potent and broader-spectrum analogs.

 

[Hope01]

Also of note is that Dr Chia presented at this conference which is obviously where he was able to discuss the research of these potential antivirals with the Rega Institute scientists.
http://europic2016.org/wp-content/uploads/2015/07/Programme-Europic-final_web.pdf
pg 133
CHRONIC ENTEROVIRUS INFECTION IN A PATIENT WITH MYALGIC ENCEPHALOMYELITIS/ CHRONIC FATIGUE SYNDROME (ME/CFS) – CLINICAL, VIROLOGIC AND PATHOLOGICAL ANALYSIS
John Chia1, David Wang2, Andrew Chia2, Rabiha El-Habbal2 1, 2EV Med Research

 

[Hope01]

Interesting that Itraconazole continues to come up for enterovirus inhibition.
As noted on pg 150
A STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF ITRACONAZOLE, A NOVEL ANTIVIRAL COMPOUND THAT TARGETS THE OXYSTEROL BINDING PROTEIN
Lisa Bauer, Lucian Albulescu, Jeroen R.P.M Strating, Frank J.M. van Kuppeveld University Utrecht

And in these papers provided by hip under his list of Antiviral Drugs for Coxsackievirus B
https://www.ncbi.nlm.nih.gov/pubmed/25640182
https://www.ncbi.nlm.nih.gov/pubmed/25691649

Also in:
Replication and Inhibitors of Enteroviruses and Parechoviruses
http://www.mdpi.com/1999-4915/7/8/2832/htm#B193-viruses-07-02832

Does anyone know of Dr Chia trialling this before?

 

[Nickster]

Interesting that Itraconazole continues to come up for enterovirus inhibition.
As noted on pg 150
A STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF ITRACONAZOLE, A NOVEL ANTIVIRAL COMPOUND THAT TARGETS THE OXYSTEROL BINDING PROTEIN
Lisa Bauer, Lucian Albulescu, Jeroen R.P.M Strating, Frank J.M. van Kuppeveld University Utrecht

And in these papers provided by hip under his list of Antiviral Drugs for Coxsackievirus B
https://www.ncbi.nlm.nih.gov/pubmed/25640182
https://www.ncbi.nlm.nih.gov/pubmed/25691649

Also in:
Replication and Inhibitors of Enteroviruses and Parechoviruses
http://www.mdpi.com/1999-4915/7/8/2832/htm#B193-viruses-07-02832

Does anyone know of Dr Chia trialling this before?

An antiviral that has come up is "Pleconaril" to treat enteroviruses. Has anyone heard of this antiviral?
My son saw Dr Chia last August and the only thing he gave him was equilibrant.

 

[JES]

An antiviral that has come up is "Pleconaril" to treat enteroviruses. Has anyone heard of this antiviral?
My son saw Dr Chia last August and the only thing he gave him was equilibrant.

Pleconaril was rejected over a decade ago by FDA due to side effects. Coxsackievirus antiviral drugs are listed in this thread. Of those, only umifenovir, fluoxetine and oseltamivir have demonstrated antiviral effects against CVB4, which is the enterovirus that is likely the problem for most.

 

[Hip]

Hi all, after researching the August Europic 2016 meeting on picornaviruses & enteroviruses in Switzerland, http://europic2016.org/wp-content/uploads/2015/07/Programme-Europic-final_web.pdf
I think I have come across the new CVB4 antiviral drug from the Rega Institute in Belgium. This is on pg 139 of the pdf. I highly recommend for those with chronic enterovirus infections to read/at least browse to the relevant topics in this pdf summary of the conference, it is incredibly detailed but it is the most up to date research/information on enteroviruses there is currently in the medical/ research world.

Good find, Hope01.

That pdf document, covering the 19th International Picornavirus Meeting in September 2016, is indeed a veritable compendium of much of the latest enterovirus / picornavirus research. I have had a quick scan of it already.



The anti-CVB4 drug mentioned in the first study you quoted above (from page 139 of that pdf) refers to "compound A" which it says is a proprietary enterovirus 2C protein inhibitor.

That "compound A" could be the anti-CVB4 drug in question, but Dr Chia did say the anti-CVB4 drug has a code name comprised of letters and numbers (many drugs in development do), so if this "compound A" is the potent anti-CVB4 drug Dr Chia was talking about, they must have given it a code name since the time of this International Picornavirus Meeting.

Likewise for the "compound 17" mentioned in the second study you quoted.





@JES, here are the enteroviruses that Dr Chia finds most commonly associated with ME/CFS:

• CVB3 and CVB4 first and foremost

• Then CVB2, EV6, EV7 and EV9

• And then much less EV11

Source: here.

 

[halcyon]

The anti-CVB4 drug mentioned in the first study you quoted above (from page 139 of that pdf) refers to "compound A" which it says is a proprietary enterovirus 2C protein inhibitor.

That's likely the one. When I spoke to Chia last he mentioned that there are two promising compounds, both have been purchased by drug companies for development. One inhibits 2C and one inhibits 3Dpol.

 

[Dechi]

Dr. Hyde is definitely still actively seeing patients. He also just recently updated his Nightingale definition, tying the disease much more closely with enteroviruses than he has in the past. This is one of the best modern descriptions of the disease that I've seen. He also presented this at IACFS/ME and to Maureen Hanson's team at Cornell late last year.

Dr Hyde strongly believes enterovirus are the main cause of ME. He is still seeing a few patients and I am lucky to be one of them.