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.
