[opensourcepharma] a open source cure for Ebola?

Thu Aug 7 13:57:50 UTC 2014

Just getting caught here as I was away at a Gordon conference this week.  I like the idea of crowd sourcing information using a Wiki format.  I can contact NIAID and see what resources they are deploying or gathered.  I will have to read through The papers Bernard has cited to see what was screened to find these compounds. I would guess nobody has screened a repurposing collection as large as the one we have so that might be worth doing.  The catch is this must be BSL4 level of containment and our facility can only go to BSL 2. NIAID has a faculty for BSL3 and. 4 screening so that would be an option.  When I get back to the office I will look into how interested people are in this.  When people were coming down with CM after IT injection of steroids contaminated with fungus we were able to complete a screen and release data in a publication in about 3 months from outbreak.  In that case we did not find anything new.

On another note I introduced the concept of a Gordon Med Chem session on Open Source  Drug Discovery and Development at the planning session last night.  At first the idea was met with complete silence but after I sold it to the group I was able to gain enough enthusiasm to get this accepted into the next stage of decision making.  I will let everyone what I hear next.  As Matt mentioned at Bellagio this is primarily a very conservative group of med chemists so this was a nice surprise.
John

Sent from my iPhone

On Aug 7, 2014, at 8:22 AM, "Els Torreele" <els.torreele at opensocietyfoundations.org<mailto:els.torreele at opensocietyfoundations.org>> wrote:

http://www.nytimes.com/2014/08/07/world/africa/who-weighing-emergency-decree-on-ebola.html

*Expert Panel to Consult on Ebola*

*By **RICK GLADSTONE*

<http://topics.nytimes.com/top/reference/timestopics/people/g/rick_gladstone/index.html>

AUG.

6, 2014

Scrambling to catch up with the worst outbreak of the deadly Ebola virus, the World Health Organization announced Wednesday that it was considering the declaration of an international public health emergency and would convene a panel of experts in coming days to explore the use of experimental treatments for the incurable disease.

<SNIP>

The health organization said an emergency committee of international experts was evaluating whether the Ebola outbreak constituted a “Public Health Emergency of International Concern,” a classification that has only rarely been invoked to combat deadly contagions. The classification gives health authorities greater powers that include quarantining people in affected areas. The committee’s recommendations are expected by Friday.

In a separate announcement

<http://www.who.int/mediacentre/news/statements/2014/ethical-review-ebola/en/>,

the organization said it was convening a panel of medical ethicists to explore the use of experimental treatments for Ebola, which has a mortality rate as high as 90 percent. The virus causes high fevers, aches and severe internal bleeding.

“We are in an unusual situation in this outbreak,” Dr. Marie-Paule Kieny, the W.H.O.'s assistant director general, said in the announcement. “We need to ask the medical ethicists to give us guidance on what the responsible thing to do is.”

Several experimental options are under development, including a drug administered to two Americans <http://www.samaritanspurse.org/article/samaritans-purse-doctor-serving-in-liberia-west-africa-tests-positive-for-ebola/>who

had been working with Ebola patients in Liberia through Christian relief groups. Both were flown to Emory University Hospital in Atlanta and have shown improvement, causing an international debate over why Americans were given the drug when hundreds of Africans have died without access to it.

The W.H.O.'s announcement also cited the relief group workers’ apparent response to the drug, saying it had “raised questions about whether medicine that has never been tested and shown to be safe in people should be used in the outbreak and, given the extremely limited amount of medicine available, if it is used, who should receive it.”

Asked about such treatments, President Obama told a news conference in Washington it was premature for him to say, but he did not rule it out.

“We’ve got to let the science guide us,” he said.

From: opensourcepharma [mailto:opensourcepharma-bounces at lists.okfn.org] On Behalf Of Bernard Munos
Sent: Thursday, August 07, 2014 2:49 AM
To: Jaykumar Menon, Prof.
Cc: opensourcepharma at lists.okfn.org<mailto:opensourcepharma at lists.okfn.org>
Subject: Re: [opensourcepharma] a open source cure for Ebola?

Perhaps we could approach the authors of the papers I listed earlier about joining a science advisory board that could help identify the repurposing candidates with the best potential. These scientists also have access to tools (e,g, assays) that could come in handy in evaluating new candidates, if need be. Key thing: we must be careful about how we communicate, and not promise a drug before we have one. There are too many examples of things that work in the lab, but not in humans.

b

On Thu, Aug 7, 2014 at 12:38 AM, Jaykumar Menon, Prof. <jaykumar.menon at mcgill.ca<mailto:jaykumar.menon at mcgill.ca>> wrote:
I agree with all.  The entire world’s attention is on Ebola.  When does a neglected disease ever get so much attention?

If we can come up with a concept/project that is rapid, sound, high profile, understandable, of real substance, with an element of drama/suspense, maybe with a mass participation element (e.g crowdsourcing ideas, and maybe citizen scientists and lay citizen too), and within our abilities, that would be huge and capture the planet’s imagination.    And we may be just nimble enough to conceive of it.

The overall idea seems pretty nice and simple:  Open source pharma – fast new cures for Ebola.

Once conceived/written, there could be funder interest.

Would show all that there is an open source alternative.  Reminds me of when we did the Ocean Oil Spill Clean Up X Prize.  We drafted an idea, got funding in 1-2 weeks from a google co-founder, and were a huge global event, playing out over the next 9 months.   Our usual process was years.

As old chairman Mao once said (when not committing serious crimes)  Dare to Win.

J

From: opensourcepharma [mailto:opensourcepharma-bounces at lists.okfn.org<mailto:opensourcepharma-bounces at lists.okfn.org>] On Behalf Of Matthew Todd
Sent: Wednesday, August 06, 2014 9:27 PM
To: opensourcepharma at lists.okfn.org<mailto:opensourcepharma at lists.okfn.org>

Subject: Re: [opensourcepharma] a open source cure for Ebola?

I would guess that there are three strands to this idea on Ebola, in order of immediacy:
1) Survey the current state of what's being evaluated already
2) Assess potential molecules that could be repurposed, e.g. molecules that are approved for related infections, or those that have shown some efficacy but have not been developed further
3) Propose ways of generating new hits from new screens.
I'm assuming that the first step is 1) (and maybe a little bit of 2), but that 3) is too much. So we need a survey of the current state of knowledge. That seems to me to be something that could be crowdsourced, since it's an information gathering task - essentially a review of where we stand. Bernard already brought up many key pieces of information.
In my experience the way to assemble the state of a field using multiple contributors is to use a wiki, so that anyone can contribute to the writing and the writing can be kept up to date. A wiki usually comes with a "talk" page to allow people to discuss edits, or a separate community could be set up quickly. Wikipedia itself doesn't really host "live" pages with primary content, but sticks rigorously to secondary sources, so it may be necessary to use a different site, but WP's user base would be perfect for this. Once it's started in the open, we can bring in people with insider knowledge of the field.
If some agency were willing to sponsor a few small prizes for writing quality, that might stimulate considerable interest from student participants, particularly given how current this is. e.g. $100, $500 and $1000 prizes for the highest quality contribution(s) judged by a panel in one month's time. The fact that this is in the news right now as a serious public health problem should help to raise awareness. We would need a few people to act as mentors for the writing, pointing out what's needed, or resolving disagreements etc with a light touch.
Once the review is done, that should help planning of what to do next, be that approaching funding agencies, or crowdsourcing something more targeted to trial design etc. There could even be a voting process for where to focus further research in the short term.
Tomasz do I have that right, that this would be the necessary first step(s) for what you suggest? i.e. to help the decision making process? Having TLS interested in taking this further would make the analysis of the current status of the field part of something bigger. Bernard  - the chance to critically evaluate the current trials that are underway: do you see that as adding something on top of the public domain knowledge about the trials that are active that you already found? e.g. discussion about other possible therapies that have been considered and abandoned?

Best,

Mat

On 6 August 2014 20:28, Tomasz Sablinski <tomasz at transparencyls.com<mailto:tomasz at transparencyls.com>> wrote:
Hi Bernard,

This is the concept, indeed. A crowd - sourced, well defined plan. Financing the execution, and study conduct itself would be subject of consultation with the players you mention and probably some others interested in paying for it.

regards,
Tomasz

On Wed, Aug 6, 2014 at 6:44 PM, Bernard Munos <bhmunos at gmail.com<mailto:bhmunos at gmail.com>> wrote:
My advice would be to position it as a crowdsourcing initiative to find badly needed treatments quickly, among the store of already-approved drugs. Once such potential treatments have been identified, I would consult with MSF, DNDi, and other NGOs to identify the next steps.

b

On Wed, Aug 6, 2014 at 6:19 PM, Tomasz Sablinski <tomasz at transparencyls.com<mailto:tomasz at transparencyls.com>> wrote:
Dear All,

I am making this suggestion with a bit of trepidation, because it is such enormous task, and politically charged topic.

What if we used Transparency Life Sciences platform to engage the crowd to:
1/ identify the most suitable candidate(s) for clinical testing, along the lines suggested by Bernard via a "reversed" TLS Indication Finder
2/ design the simplest and most feasible clinical research protocol using TLS Protocol Builder

We know how to curate and make sense of crowd contributions counting hundreds. I imagine that the name Ebola would attract thousands. Our survey technology can handle such numbers, we just haven't done it yet. This effort would require some $$ for IT, etc, and expert(s) from CDC (?), WHO (?), etc to "curate" the crowd.

I would see this as joint Open Source Pharma and TLS project. I think it fits both organization visions nicely, and the social impact and example to th world could be tremendous.

Please let me know what you think, and also understand that I am throwing this idea ad hoc, and can not make a firm commitment before we figure out details.

Regards,

Tomasz

On Wed, Aug 6, 2014 at 5:58 PM, Bernard Munos <bhmunos at gmail.com<mailto:bhmunos at gmail.com>> wrote:
There are several publications in PLoS and Science TM suggesting that at least half a dozen approved drugs have some degree of efficacy against Ebola (here<http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0060579&representation=PDF> and here<http://stm.sciencemag.org/content/5/190/190ra79.abstract?sid=ecf907f6-a4ae-4b37-a29d-474963a53068> and here<http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0060579>). However, they have never been tested in humans (hard to find patients outside epidemics). By law, FDA may not disclose which drugs have been submitted for approval. However, this is not a problem because any application has to rely on human trials that must be registered on clinicaltrials.gov<http://clinicaltrials.gov>. In this case, a quick search<http://www.clinicaltrials.gov/ct2/results/displayOpt?flds=a&flds=b&flds=f&flds=c&submit_fld_opt=on&cond=Ebola&show_flds=Y> shows 9 trials -- 5 phase 1 vaccine trials sponsored by NIH; 4 phase 1 drug trials sponsored by Sarepta, Tekmira, and NIH. No human trials on repurposed dugs yet, although that could change, with the situation. Since no phase 2 and 3 trials have been registered, no Ebola drug could have been submitted for approval in the US.

Sending unapproved drugs to Africa is fraught with ethical concerns about using Africans as guinea pigs. US was correct to treat its own citizens first to avoid that charge. My guess, however, is that it might respond favorably if it were to receive a request from African government(s) for experimental treatments. These governments can also offer repurposed drugs to their patients, if they wish, since they are generic, inexpensive and widely available.

The positive development in all that is that the drug developed by Mapp Biopharmaceutical is a monoclonal antibody produced in genetically-modified tobacco plants. This is a new technique that can produce kilo quantities rather cheaply, as opposed to the very expensive gram quantities produced by traditional cell culture. So this Ebola disaster might end up validating a new technique that will upend the economics of monoclonals, by far the most expensive drugs today. The impact on biosimilars, oncology, inflammation, etc, could be huge.

b

On Wed, Aug 6, 2014 at 4:33 PM, Els Torreele <els.torreele at opensocietyfoundations.org<mailto:els.torreele at opensocietyfoundations.org>> wrote:
It’s been fascinating to read some of the commentaries on the fact that we don’t have a treatment against Ebola virus, eg:
http://www.vox.com/2014/8/4/5963751/the-real-cause-of-the-ebola-outbreak-its-not-what-you-think

As well as that there seem to be a few experimental treatments around, but all is shrouded in secrecy
http://www.aljazeera.com/news/africa/2014/08/experts-give-new-us-ebola-drug-africans-201485233636516828.html
http://www.cdc.gov/vhf/ebola/outbreaks/guinea/qa-experimental-treatments.html
“ The FDA cannot comment on the specifics of ongoing drug development programs and cannot reveal information that is not otherwise public concerning submissions covering such programs such as IND applications submissions.”

Wouldn’t this be a great opportunity for open source drug R&D, including crowdsourcing ideas, to speed up the discovery of a desperately needed new drug. Instead of having a few companies working privately on their own (with US gov support often), we could imagine opening it all up, share what we know about the virus, about the potential drug candidates out there, and then together build upon shared knowledge and progress?

Els Torreele, PhD
Director, Access to Essential Medicines Initiative
Public Health Program
Open Society Foundations
224 West 57th Street I New York, New York 10019
Tel: (+1)-212-548-0351<tel:%28%2B1%29-212-548-0351> I M: (+1)-646-262-2053<tel:%28%2B1%29-646-262-2053>
els.torreele at opensocietyfoundations.org<mailto:els.torreele at opensocietyfoundations.org>
http://www.opensocietyfoundations.org/topics/access-medicines

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