Battling Zika: A Biotechnological Approach

By Glenn Petrie, Ph.D.
Senior Scientific Advisor
ABC Laboratories

www.abclabs.com

Zika is a disease caused by the Zika virus which is spread to humans primarily through the bite of an infected Aedes species mosquito. The disease can also be by transmitted through sex with an infected partner. The symptoms of Zika are fever, rash, joint pain, and conjunctivitis. The illness is usually mild with symptoms lasting for several days to a week and rarely requires hospitalization. There is no vaccine or specific treatment for Zika virus infection. Treatment is symptomatic and supportive, including rest and the use of acetaminophen to relieve fever.

Federal health officials recently confirmed that the Zika virus causes a rare birth defect and other severe fetal abnormalities, typically, abnormally small heads and severe brain defects. There is also limited evidence of Guillian-Barre’ syndrome and multiple sclerosis being related to Zika infection. The greatest risk is to pregnant women; however the Center for Disease control has recommended that men and women should wait a minimum of 8 weeks after possible exposure before trying to conceive. This period may increase based on the latest findings regarding the latency of the virus.

In a recent article in The New England Journal of Medicine it was noted that Zika is the fourth mosquito-borne illness to infiltrate the Western Hemisphere over the past 20 years, following dengue, West Nile, and chikungunya. There is currently no available vaccines for any of these diseases. According to the World Health Organization (WHO), more than 60 research institutes and companies are working on products to combat the spread of the Zika virus, but a vaccine is likely to take years to develop.

The disease can alternatively be attacked by control of the vector, Aedes aegypti. WHO states that traditional insecticide spraying methods have had no significant impact in decreasing the spread of dengue, implying that these classical methods for battling mosquito borne disease may be equally ineffective for Zika.

There is another possibility for eradicating the Aedes species mosquito over large areas. This involves modification of the mosquitos themselves. This approach has been used successfully in the past for eradication of the screwworm, an insect that was a major cause for livestock deaths in the mid- 20^th century. The screwworms were irradiated, sterilizing the male flies. Only the male flies were released, typically sprayed from small planes. The sterile males could not produce progeny, gradually eradicating the species. The technique was an unmitigated success.  The last cases of screwworm in the United States were reported in 1982, followed by eradication in Mexico and Central America.

Now, the world is focused not only on the Zika virus, but dengue, chikungunya and yellow fever, all transmitted by Aedes aegypti .  A British company, Oxitec, has approached the problem utilizing genetic engineering and inserting a gene that kills the insect. Male mosquitoes containing the gene are released to mate with wild females. The released male mosquitoes have no effect on people because males don’t bite. Offspring die before they reach adulthood, in that way suppressing the population of wild mosquitoes. Small-scale tests conducted in the Cayman Islands, Panama and Brazil since 2009 reduced local mosquito populations by as much as 99 percent.

Last month the federal government tentatively approved a field test (Florida Keys) of genetically engineered mosquitoes that might help slow the spread of the Zika virus. A final approval for the trial will not be made until the FDA receives and assesses comments from the public, which is likely to take months and the plan has faced fierce opposition from some residents in the state.

Information for this article was obtained from The Washington Post, The New York Times, The New England Journal of Medicine, CDC website and WHO website.

Biosimilars: They May Look the Same, but One is a Real Stinker

Biosimilars by nature look much like their comparator products, but they sometimes behave quite differently. That’s because the two products often originate from different cell lines or expression systems. And no matter how hard you strive for parity in the way they’re cultured, minor differences in manufacturing can lead to sticky variations in primary amino acid sequence, glycosylation chemical modifications and protein folding issues. The FDA understands biosimilar products sometimes behave differently than their name-brand counterparts. But, they do expect you to understand why those differences occur, and to demonstrate that they have no clinical significance. That’s where ABC Laboratories comes in.

Choosing the Right Analytical Partner May Be the Most Economically Important Decision You Make

FDA guidance calls for a “complete and thorough” CMC section that begins with extensive comparative characterization of the biosimilar and... click here for more.

I-SPY and now AGILE Cancer Programs

By Harley Everett Wilcox, MBA

Senior Scientific Advisor

ABC Laboratories
www.abclabs.com

Historical clinical cancer studies lack efficiency and require significant time for often an overall survival improvement of only 60 days versus standard treatment. The inefficiencies may be related to the need for adequate safety evaluation, single agent studies, and limited tumor biological information for individual patients.  Approval of a new oncological agents require 10-15 years of clinical drug development and in rarer cancers, patient populations available for study are lacking .New investigation drugs require evaluation in diseased patients prior to approval and often before combination with other attractive agents. With the advancements in biological test procedures, and better understanding of cancer biology, an individual tumor may be profiled to determine the theoretical optimum drugs, combination of drugs and dosing schedule.

The I-SPY program is a novel personalized cancer treatment study supported by the FDA, NIH and a consortium of pharmaceutical companies via the Foundation for the National Institutes of Health (FNIH). The design allows for investigating new drug therapies with standard treatment and flexibility to modify treatment protocols on the fly, saving time, money, and optimal treatment regimens for breast cancer patients.  Multiple company intellectual property have been combined in a single phase II like program to access the best therapy based on tumor biology and proof concept of activity prior to surgery in resistant tumor types. The goal will be to bring effective treatments to market with fewer patients and in less time.  

Targeting another type of cancer in an adaptive trial approach is MD Anderson and the recently announced AGILE study.  Glioblastoma multiform has yet to see a new chemical treatment option in ~10 years with the standard chemotherapy Tremodar and radiation providing an overall survival improvement of just 2 months.  MD Andersons’ Mitchel Burger, MD states the uniqueness of the study, like the I-SPY uses biological tumor profiling and Bayesian statistics to limit the number of clinical patients.  The statistical method allow for a probability approach to advance drug winners more quickly. As stated earlier, one issue with rare cancers is adequate patient populations for supporting multiple clinical studies. With~10,000 GBM cases a year combined with aggressive disease, brain cancer clinical programs often require longer time to complete enrollment.

These adaptive clinical trial programs will hopefully provide more meaningful outcome for clinical trial participants and more rapid approval for needed treatment options.

References:

http://ispy2.org

Target Oncology (targetdonc.com)

A Biotech Scientist Answers the Question: "Is JURASSIC WORLD Possible?"

By Glenn Petrie, Ph.D.
Senior Scientific Advisor
ABC Laboratories
www.abclabs.com

As a boy I was fascinated with dinosaurs. But while most children grew out of this by 7 or 8, I remained engrossed in all things “saurus”. As I started my career in biotechnology, I was particularly interested in Michael Crichton’s book Jurassic Park. I read it in a single sitting and went to the first showing when the movie was released. Now that JURASSIC WORLD is a worldwide phenomenon, interest in reviving extinct species, or de-extinction, has been brought to the forefront. But could JURASSIC WORLD actually be possible? The short answer is no. DNA is the key to any attempts at de-extinction, but while stable, it is not stable for millions of years. Therefore, since dinosaurs went extinct 65 million years ago, there is no viable DNA

However, DNA can survive tens of thousands of years in the right environment, particularly frozen. There are numerous articles in both the scientific and popular literature regarding bringing Wooly Mammoths back to life. Frozen carcasses discovered in Russia have yielded partially intact DNA. JURASSIC WORLD scientists use the bottom-up technique, i.e. start with a fairly complete genome and plug the gaps with that of similar species. In reality the top-down approach is more likely since only partial DNA genomes have been recovered. Scientists are attempting to modify elephant DNA with some of the mammoth’s. The goal is to obtain a hybrid, an elephant with some mammoth traits. With the explosion in biotechnology, one could envision a Pleistocene Park. Rather than dinosaurs it would be populated with animals from the Pleistocene era, ~10,000 years ago. Among the possible exhibits could be Wooly Mammoths, Saber Tooth Cats, Wooly Rhinoceros, Giant Ground Sloths and the Giant Short-faced Bear. Think of the La Brea Tar Pits brought to life.

Even if this is possible, should it be attempted (“But John, if Pirates of the Caribbean breaks down, the pirates don’t eat the tourists.”)? While no one is seriously proposing de-extinction as a theme park, many are interested in using this technology to increase biodiversity and bring back species that humans destroyed, e.g. passenger pigeon, Steller seal, Tasmanian tiger and the dodo. Since there are numerous specimens of these species throughout the museums of the world, there is a reasonable chance of success. However, many ecologists see this as a zero sum game. They believe that any money spent on de-extinction represents less money for efforts to save endangered species; protection, habitat, etc. There may be a middle ground in which de-extinction methods could be used with endangered species to increase genomic diversity and increase the chances for a healthy population.

I look forward to following the latest developments in this exciting field and will provide an update with the release of JURASSIC WORLD 2.

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