Tuesday, October 7, 2014

Developing Aerosolized TKM-EBOLA as Airborne Transmission of Ebola Likely

Knowing how a virus is spread, also from a cell biology point-of-view, is critical to curtailing its spread and devising effective treatment strategies.   

According to the World Health Organization (WHO), the first symptoms of an Ebola infection are ‘the sudden onset of fever fatigue, muscle pain, headache and sore throat (emphasis mine). Then also consider the following:

1)      Ebola once killed a number of monkeys are apparently spreading through the ventilation system in Reston, VA; 

2)      A nurse became infected in a reference hospital for infectious diseases in Spain despite the protective clothing she was wearing and her limited contacts with the infected patients she was looking after (taking temperatures twice);

3)      A single pregnant woman in Liberia infected atleast 10 people helping her as she came down with Ebola;

4)      Ebola virus can infect numerous cell types in the body (frequently cited are the liver, endothelial cells, and phagocytic cells) and is found in high amounts inthe respiratory tract in infected pigs with the virus spreading readily to cohabiting pigs in the colony;

If you still believe in the narrative, even propagated byotherwise fairly reliable sources such as the CDC, that Ebola is only transmitted by direct contact with body fluids, then you should start considering airborne transmission as a main route the infection is spread.

After all, since when are cough droplets not a bodily fluid?

If airborne is indeed an important route of transmission, this would not only raise concerns that just like in avian flu, a few mutations in the virus adapting it to better latch on to the human respiratory tract could further catalyze the spread of the virus, but would also mean that treating it at the respiratory stage could both prevent the virus from fully entering the body as well as limit its spread from person-to-person.


Enter TKM-EBOLA

An RNAi viral knockdown approach in the respiratory epithelium should obviously be able to achieve that goal.  All that would be required is to take the same RNAi triggers now part of the intravenous TKM-EBOLA formulation and incorporate it in something amenable for respiratory delivery.

Back in 2011, Tekmira revealed that it was developing aerosolized liposomal nanoparticles (LNPs) to deliver RNAi triggers to the respiratory epithelium.  A key challenge was to find formulations that not only could successfully transfect respiratory epithelial cells, but also withstand the shear forces involved in nebulizing them.  Initial structural and tissue culture RNAi knockdown results showed that this can be achieved.

The development was seemingly halted at the rodent preclinical stage as the company had to save financial resources as it was fighting off Alnylam in a trade secret case.  After coming out on top of the litigation in November 2012, the company was then able to once again expand the development of its LNP-based nucleic acid delivery technology, in addition to churning out clinical development candidates (e.g. the important HBV candidate to be revealed next week).
 
Given that the company established a separate biodefense unit headed by the ‘LNP-brain’ of the company, now Chief-Technology-Officer Ian MacLachlan, I would not be surprised if LNP nebulization was part of that effort with the next goal of showing efficacy in monkeys.


Such reformulation of TKM-EBOLA is just another example of the versatility of RNA Therapeutics, just as is the ability to rapidly adjust and optimize the medicine as the virus evolves (note: this is e.g. not possible with antibodies).  It also adds to the importance of scaling up the supply of the RNAi trigger now should airborne be recognized as a major route of transmission.  

Long-term, such developments would obviously benefit the development of LNP-delivered RNA Therapeutics for the lung epithelium in general, including mRNA delivery (e.g. for Cystic Fibrosis) and a universal RNAi agent against flu.   

8 comments:

Anonymous said...

The Spanish nurse did not have limited contact with the ebola infected patient. According to a statement from Spanish Authorities released a few minutes ago she entered the room twice. Once to do a diaper change (high risk procedure) and the second time to clean the room following the death of the patient (again, high risk procedure). She was wearing protective clothing, investigation is ongoing.

Dirk Haussecker said...

Thanks much for the added insight. Do you have a link to the statement?

Anonymous said...

Health Authorities are currently explaining the situation to the Congress. Here is a link to the live streaming...its in Spanish though:
http://www.elmundo.es/elmundotv/index.html?cid=ULTHR22001&s_kw=en_directo

Anonymous said...

http://www.businessinsider.com/will-ebola-go-airborne-2014-10

John Leavitt said...

Becky Ryzner at Nerac has written about the probability of Ebola mutating to become airborne.

http://nerac.com/ebola-do-we-need-to-worry/

The size of the epidemic in West Africa make this plausible. No doubt the CDC understands this but refrain from talking about it. I wrote an article at my blog about an exchange that occurred on the CBS morning news today. Very amusing.

http://www.woodstockctcafe.com/2014/10/07/ebola-%E2%80%9Cwhat%E2%80%99s-the-worst-scenario%E2%80%9D/

Anonymous said...

Salient NY Times article on efficacy of Chimerix drug, brincidofovir.

"What is remarkable is that the drug, with the unwieldy name brincidofovir, has never before been tested in people with Ebola, and there is not even any data available showing that it works in animals infected with the virus."

NY Times Chimerix article 10-7-2014

Anonymous said...

I see a tweet on your blog today regarding TKMR treatment of Ebola patients. The links provided give NO evidence of this.

Also there is no evidence of the virus being airborne transmitted yet you somehow moot that it could be. There isn't any proof whatsoever of this. I wish you would stick to facts and not print this rubbish. You are constantly letting letting opinion and market moves affect your reporting of facts.

Either do something about your style or call your blog for what it is. A ramping of your latest buy recommendations.

gene genie said...

All the patients who received TMK -Ebola have recovered in Western Medical Care , those who didnt have a west African survical probablity ie 50% or less inspite ICU support. If the DOD and US government fails to stock-pile and use this drug , God help us , The ultra consrvative management of this company have not released updates as the data is not the usual clinical trial format. But we would never had penicillin , streptomycin of the small pox vaccine if such conservative routines were adhered to in crisis. Tekmira - wake up.

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