Saturday, May 29, 2010

New Experimental Treatment for Ebola Zaire Shows Promising Effect in Monkeys

Scientists from the Boston University School of Medicine in collaboration with USAMRIID have developed a novel treatment for Ebola Zaire that has shown promising results and potential for treatment of humans exposed to the virus.
The study published in the Lancet titled "Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study" is a major step forward in treating Ebola exposure.

Ebola Zaire has the highest mortality rates of all the Ebola viruses at approximately 83% for all recorded epidemics.

Using small interfering RNAs (siRNAs), the authors targeted the L protein, VP24, and VP35. The L protein is the viral polymerase, and is also responsible for capping and polyadenylation of newly synthesized viral proteins making a functional L protein required for Ebola virus replication. VP24 and VP35 have both been identified as inhibitors of IFN-alpha/beta production and IFN-alpha/beta and gamma signaling. The ability of the Ebola virus to interfere with IFN production and signaling allows it to escape host immunity.

Lipid nanoparticles (LNPs) are the most widely used siRNA delivery approach. In this study, the research team used a proprietary technology called SNALP, or stable nucleic acid-lipid particles, to deliver the therapeutics to disease sites in animal models infected with Ebola Zaire.

Two test groups were established. The first group of three rhesus macaques was given anti-Ebola Zaire siRNAs intravenously, 30 minutes after exposure to the virus, and again on days 1, 3, and 5 post exposure. A second group of four macaques was given the treatment after 30 minutes, and on days 1, 2, 3, 4, 5, and 6, after challenge with Ebola Zaire.

Two of the three animals in the first group (30 min, days 1, 3, 5) were protected from Ebola and survived. All four of the monkeys given treatments (30 min, days 1, 2, 3, 4, 5, 6) survived. The only side effects observed in either study were elevated liver enzymes which could have been an artifact from the viral infection itself.

This study represents the first demonstration of complete protection against a lethal human infectious disease in nonhuman primates using RNAi, according to lead author Dr. Thomas W. Geisbert of the Boston University School of Medicine. Dr. Thomas Geisbert and his wife Joan are highly revered experts in the Bio Safety Level-3 (BSL-3) and BSL-4 world doing research on Ebola, Marburg, and others.

Geisbert believes their work justifies the immediate development of Ebola SNALP as a countermeasure to treat Ebola infected patients, either in outbreaks or accidental laboratory exposures. Obviously, clinical trials are difficult in any situation involving a life threatening virus so in order for this to be tested, an outbreak will have to occur. It will be interesting if this therapy will ever be used in the field, and if that opportunity presents itself, how effective it will be in humans.

Ebola virus exists as 5 strains and causes hemorrhagic fever (Reston and Tai, only in monkeys). The virus, which can be infectious by aerosol, but far more contagious via blood and body fluids, is of concern both as a global health threat and a potential agent of biological warfare.

Currently there are no available vaccines or therapies for Ebola, therefore researchers working with the virus have to observe maximum containment (BSL-4) rules. BSL-4 personnel wear positive pressure "space suits" breathing filtered air as they work, and all laboratory waste streams are sterilized.

The SNALP-RNAi therapeutic used in the study was developed by Tekmira Pharmaceuticals Corporation of Vancouver, BC. Previous research showed that these siRNAs completely protected guinea pigs when administered shortly after a lethal dose of Ebola Zaire was administered. Further studies in monkeys will be necessary to refine dosing, toxicology and other issued before the treatment could be licensed for human use.

"The significance of this report goes beyond the protection against Ebola virus," said COL John P. Skvorak, commander of USAMRIID. "It also represents the potential for this concept to be applied to other viral infections."

On a personal note, I am very excited about the potential for this treatment to be successful. I have always been interested in doing more "exotic" viral research and knowing there is a treatment potentially available is a major step forward for treating outbreak victims.

Lance D. Presser has a PhD in Microbiology & Immunology, and is a Public Health Laboratorian.

Tuesday, May 25, 2010

New Director of the Center for Biopharmaceutical Research and Production at North Dakota State University

North Dakota State University has hired a new Director of the Center for Biopharmaceutical Research and Production at NDSU. C. Satishchandran will head the center, of which the focus will be DNA vaccine identification and production. He will also be a tenured professor of pharmaceutical sciences and have teaching responsibilities. Satishchandran came directly from the Nucleic Acid-Based Therapeutics Division of the Biotherapeutics Division at Pfizer Inc. where he was the Chief Technology Officer.

Satishchandran’s base annual salary is going to be $225,000, making him the second-highest-paid employee at NDSU, behind only the president, according to NDSU payroll information for 2009-10 (the new President hired May 24th 2010 will make a base salary of $300,000 and the NDSU head football coach makes a base salary of $180960 but his additional camps, radio appearances, and promotions can exceed $300,000).

Higher education and economic development officials have been working to bring a cluster of vaccine and related biotechnology firms to Fargo-Moorhead to build on academic programs already here. Biotechnology firms already in place include Aldevron, which recently acquired German vaccine company Genovac, as well as the new to Fargo, AltraVax.

Satishchandran stated in a news release his goals are recruit talent, develop investments, facilitate research, and to develop at least one vaccine during the center’s first five years, followed by at least one vaccine each year after that. A pretty lofty goal.

Ideally, the center will focus on public health issues that affect people locally, such as West Nile virus, as well as globally, such as malaria.

C. Satishchandran Ph.D., has had a long and outstanding career. Dr. Satishchandran received his M.S. in Microbiology from the University of Baroda in India. He then went on to achieve his Ph.D. in Molecular Biology and Biochemistry from Memorial University of Newfoundland, Canada. He next moved to the Fox Chase Cancer Center and was there as a Post-Doc and Research Associate for roughly 6 years. Next he served as a Sr. Research Fellow, Associate Director, and Acting Director at Apollon and Wyeth (Apollon was acquired by Wyeth in 1998 and Wyeth was subsequently purchased by Pfizer in 2009). After leaving Apollon/Wyeth in 2000, he co-founded his own company Nucleonics, Inc. where he held the titles of Executive VP & Cheif Operating Officer. This lasted five years until there were charges of data falsification brought against him. Originally fired, Dr. Satishchandran and his co-founder Catherine Pachuck sued the company for wrongful termination, where they were then countersued by Nucleonics for alleged scientific misconduct.

After a brief (less than 2 years) stay at Pfizer, Dr. Satishchandran was hired by NDSU for his current position.

Being an alumni of NDSU, I sincerly hope that Dr. Satishchandran can follow through on his promises to NDSU. I have two major concerns. Obviously my first concern are the charges of misconduct. I am all for innocent until proven guilty, however I feel as though science is a lot like the current situation in major league baseball. Everyone is guilty of cheating until proven innocent. There are so many ways to manipulate data, and with the funding situation as poor as it is for academics and the millions and potentially billions of dollars at stake in new drug/vaccine development, cheating is to be expected. Second, I hope that this wasn't a situation where Dr. Satishchandran knew he was about to be canned and put out his hook for whoever would take him.

Whatever the situation, I wish both NDSU and Dr. Satishchandran the best of luck and will be carefully watching how this new center develops.

Lance D. Presser has a PhD in Microbiology & Immunology, and is a Public Health Laboratorian.

Vertex Reports Strong Late-Stage Hepatitis-C Drug Data

In a report by the Wall Street Journal, Vertex reports some nice results from the first of three highly anticipated anti-HCV drug trials. The study included 1095 people with HCV genotype 1 which is the most common form of the virus found in the U.S. and Europe. Genotype 1 is also the most difficult to treat and has the lowest success rate of any of the 11 major types.

The data shows that 75% of subjects taking teleprevir (a protease inhibitor) for 12 weeks along with standard therapy for 12 weeks + an additional 12 weeks (24 total weeks of standard therapy*) achieved a sustained virological response (SVR) which is not complete elimination of the virus but is defined as the suppression of virus to undetectable levels. As compared to the control subjects who recieved the standard therapy*, achieved an SVR of 44%. Unfortunately, it is expected that the cost for the drug regimen will cost in the 10's of thousands of dollars. The other important thing to remember is like HIV, HCV is an RNA virus which means rapid mutation, which means rapid selection for resistance to drugs. It is a step in the right direction, and as more drugs are synthesized, cocktails can be changed to adapt to the mutating virus.

These findings are key for 3 reasons:
1. Increase of 31% in the treated subjects of SVR
2. Treatment is shortened from 48 to 24 weeks
3. Very minimal side effects (rash, anemia)

The results from 2 other large trials will be reported by Vertex in the 3rd quarter. Vertex plans on marketing the drug by itself, with overseas help form Johnson & Johnson. Numerous other companies are working on HCV therapeutics including Bristol-Myers Squibb Co., Gilead Sciences Inc., Roche Holding AG, and Abbott Labs.

The major alternative therapy for HCV is milk thistle (silymarin) may have various benefits to the liver, such as:

•Promoting the growth of liver cells
•Fighting oxidation and oxidative stress
•Inhibiting inflammation

Thus far, few scientific studies have found evidence that milk thistle helps in treating HCV. Some studies showed a possible benefit, while other studies have not.

Polyak SJ, Morishima C, Hawke R, Antiviral effects of silymarin against hepatitis C: the jury is still out., Hepatology (Baltimore, Md.) 48: 1, 345-6, Jul, 2008.

* Standard therapy is currently Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b (brand names Pegasys or PEG-Intron) and the antiviral drug ribavirin for 48 weeks

Lance D. Presser has a PhD in Microbiology & Immunology, and is a Public Health Laboratorian.

First Post

I just want to say hello to everyone. This is the first post. This blog will be primarily about scientific news stories, thoughts, and ideas. I guarantee I will stray from this from time to time. I am also unsure at this point in time how often it will be updated. To start, I will be aiming for once a week, and I will try to maintain at least this pace, but I hope to make it more frequent.

Lance D. Presser has a PhD in Microbiology & Immunology, and is a Public Health Laboratorian.