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;
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.
7 comments:
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.
Thanks much for the added insight. Do you have a link to the statement?
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
http://www.businessinsider.com/will-ebola-go-airborne-2014-10
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/
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.
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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