Bugs: today, tomorrow and how we might beat them!

By Stephen B. Shrewsbury
This first appeared in the February 2015 issue of DOTmed HealthCare Business News (Feature: Infection Control February 2015 p 32)

If you thought evolution has had its greatest effect upon homo sapiens, higher mammals or even all vertebrates, think again. Possibly evolution is best-utilized by those invisible microbes we have been waging war against for millennia. Great strides were made in our favour with the understanding of antisepsis. That improved understanding was used by James Lister, Florence Nightingale and others to reduce mortality from communicable disease. Then it seemed we might even have won that war when Alexander Fleming happened upon penicillin.Alas, despite the numerous antibiotics developed in the last 80+ years, bacteria are gradually fighting back against our best medicines. MRSA (Methicillin resistant Staphylococcus aureus), is perhaps the best known of these resurgent bugs, but by no means the only one. Many bacteria that we thought we had beaten have evolved by acquiring resistance capability from other species, or developing it themselves as a result of evolution — survival of the fittest.But what about viruses? The recent —and ongoing — outbreak of Ebola in West Africa caught media attention for a while. But while the media has moved on to other news stories, the death toll in Liberia, Sierra Leone and Guinea continues to rise. As yet, no effective antiviral has been rushed to these countries to treat those afflicted; and no vaccine is currently approved to protect those brave health care workers who don protective gear to treat and nurse the sick, or vaccinate the teams now collecting and disposing of the dead. How can we beat these new viral killers that may jump species and afflict homo sapiens?There is hope.

Actually both bacteria and viruses, like homo sapiens, have genes and from those genes (mostly DNA-based), come messages — messenger RNA. These messages are the blueprints that lead to the manufacture of new proteins. In the case of bacteria, they make the proteins themselves. Viruses are more nefarious; they hijack the machinery of the host (us, homo sapiens) and get our cells to make the proteins they need to replicate and spread.

A new type of medicine, called therapeutic oligonucleotides, oligos for short (or gene patches), are currently in research and early development from a whole range of small companies. These drugs are microscopic snippets of synthetic DNA that can actually bind to and block these RNA messages and halt the disease. Back in 2011, while working at AVI BioPharma (now Sarepta Therapeutics) I led a program testing an anti-Ebola gene patch in human safety testing. The results of that work were recently published and suggest that the drug was well tolerated.

Further work showed the oligo was very effective when given to primates. Without it, Ebola was lethal, but with the oligo, most of the primates survived a lethal dose of Ebola virus. The Sarepta development program was funded by the U.S. government. Alas, the shutdown of government caused that program to be shelved at the time — very regrettable in hindsight.

Another company, Tekmira, also has an oligo in development against Ebola. It is about three years behind Sarepta. Its oligo is built differently, so is unlikely to have the same safety profile. But these anti-Ebola oligos may be the best chance doctors have of beating the virus once someone has been infected, if that infection can be detected and treated soon enough. Ultimately, to beat Ebola on a nationwide or global basis, an effective vaccine is our best hope, by providing protection through immunization, to a whole population.

But what of other bugs: New viruses that spread from animals to humans, as they will almost certainly do? Or old bacteria acquiring resistance against our best antibiotics? How can we beat them? Again, gene patches may provide us with the best chance of beating these new killers.

The exact DNA (or RNA) sequence of the microbe’s genome can be mapped, much as it can be now for homo sapiens. Along with that mapping, scientists can identify the specific sequence of letters within specific genes that code for the microbe’s most important proteins. A highly precise, complimentary “patch” can then be built to those exact letters, which will stick to them and prevent their message being read. Even more importantly, these therapies can be built in a matter of days (as Sarepta has twice demonstrated when requested) — rather than the years it takes to discover and produce other antimicrobials — so they are very appropriate for new, emerging diseases.

The days of the oligo are fast approaching, not just for beating rare disease, but for turning the tide against our old enemy — the microbe.

Feature: Infection Control in DOTmed Healthcare Business News February 2015

Ebola – can we beat that bug?
The following article was the third of 3 parts to be published in “The Boomer Times” (www.babyboomers-seniors.com) January 2015:

The genes from bacteria and viruses can be sequenced, just like our genes, in a few days. Scientists can devise patches for key sections of specific genes and generate oligonucleotide patches, and then test them, in a week. Building these drugs is as “simple” as following a recipe, the sequence of letters in the section of microbial gene. For instance my former company Sarepta developed a patch against Dengue fever in 11 days at the request of the US Department of Defense!

At least two companies have now built and performed safety testing for gene patches against Ebola in healthy human volunteers with encouraging results. Efficacy testing with these gene patches in primates has seen 100% lethality turned into close to 100% survival.

As old bugs become resistant to new drugs, or new viral killers like Ebola emerge, at last we have a way to potentially combat them. Yes, you can now Defy Your DNA, but importantly you can also defy the DNA of your worst enemy! Interested? Read about these amazing new medicines in my book: www.defyyourdnabook.com

Ebola – can we beat that bug?
The following article was the second of 3 parts to be published in “The Boomer Times” (www.babyboomers-seniors.com) December 2014:

The pharmaceutical industry has become shy of trying to develop new antimicrobials. The cost of development is too great and likely return for short treatment courses against specific organisms too little to make it viable. That is not greed – that is the hard reality of the complex and increasingly costly world of drug development.

Given this depressing battle between man and microbe, where can we seek any solace? In a recent book, Defy Your DNA, a glimmer of hope appears. Both bacteria and viruses (as well as fungi) have genes. Their genes have the same basic structure as our genes – DNA. In some viruses the genes are actually made up of the very similar RNA. Gene patches, small snippets of synthetic DNA can bind to the messages that come from these microbial genes. The messages that otherwise lead to the manufacture of ultimately lethal proteins are blocked, allowing our body’s defense mechanisms time to defeat these invaders.

Previous generations of antimicrobials drugs have taken years of research and then more years of careful testing in animals first, then healthy human volunteers and lastly, infected patients. Not infrequently new drugs have taken 10 years or so to reach the market, with half of that time spent designing the drug. The new gene patches have the potential to cut down these development down times considerably. …………