The company has signed a licensing agreement with the University of North Carolina at Chapel Hill for the technology and will start offering HDClean in February.

Stephen Eckel, PharmD, and William Zamboni, PharmD, PhD, cofounders of ChemoGLO, say each packet of HDClean has two towlettes, each containing a novel mixture. When used in sequence, the towlettes can remove all detectable anticancer drug contamination commonly found on surfaces in places that prepare and administer chemotherapy, such as hospitals, pharmacies, clinics, and labs.

“This contamination is very difficult to clean up because these drugs have very different solubilities,” says Zamboni, an associate professor at the School. “If you use just alcohol or just water, or even a mixture of the two, you can’t clean up the drugs.

“We worked through a bunch of different mixtures and ingredients to come up with towlettes that can clean a wide variety of drugs. We wanted to be able to clean up many different types of drugs, and we didn’t want any strong odor or oily residue. HDClean achieves all of those goals.”

Chemotherapy contamination has been a growing topic of concern in the United States. Eckel, the assistant director of pharmacy at UNC Hospitals and a leading expert on the issue, says studies have found that people involved in the preparation and administration of chemotherapy drugs are at risk of developing complications from the hazardous drugs.

Eckel and Zamboni began the work that eventually led to ChemoGLO in 2008, developing a reference lab and an easy-to-use wipe kit to detect surface contamination of anticancer drugs. In the past three years, that kit has been used in more than one thousand tests at more than three hundred hospitals in the United States. Eckel and Zamboni say 80 to 90 percent of the institutions they’ve tested had detectable surface contamination, and many had contamination levels that were ten to a hundred times higher than the concentration needed to kill cancer cells in vitro.

The idea to develop HDClean grew out of the company’s test results, which showed that in most cases, although implementing best practices such as using closed-system transfer devices helped reduce the amount of surface contamination, it didn’t eliminate all detectable concentrations.

“The idea for HDClean is that it would clean up, at the end of the day or the shift, any remnant that wasn’t mitigated through best practices,” says Eckel, an adjunct assistant professor at the School. “HDClean should not be used in place of best practices, but it provides one more solution to minimize the contact an individual has with hazardous drugs.”

• The story behind ChemoGLO
• Learn more about ChemoGLO and chemotherapy contamination at the company website
• Check out the School's spinoff companies

There is a need to identify potent and selective inhibitors of p70S6 for use in biomedical research, Fourches says. He plans to analyze and model all known p70S6 kinase inhibitors with advanced cheminformatics technologies. He will then use the most predictive models to screen virtual libraries of compounds to identify new p70S6 inhibitors. Fourches says the research could eventually help develop new treatments for cancer, obesity, and diabetes.

Fourches has been a member of the faculty in the School’s Division of Chemical Biology and Medicinal Chemistry since 2010. Before that, he completed a postdoctoral fellowship at the School.

Mumper was recognized along with other recipients during a half-time ceremony at the men’s basketball game against Virginia Tech on Saturday, February 2. The award will be formally presented by Chancellor Holden Thorp at a banquet at the Carolina Club in April. Mumper is the School’s vice dean and the John A. McNeill Distinguished Professor.

“Both his students and his faculty colleagues were enthusiastic in their praise of Dr. Mumper’s commitment to the highest standards of teaching,” Thorp says. “He has clearly provided his students with a rich, supportive environment for higher learning.”

Mumper joined the School in 2007 after eight years as a faculty member in the Department of Pharmaceutical Sciences in UK’s College of Pharmacy. While at Kentucky, he was recognized by the UK Alumni Association as one of six Great Teachers, the oldest continuously given award for teaching at the university.

“The effects of Dr. Mumper’s teaching efforts are felt well beyond his own classroom,” says Bob Blouin, PharmD, dean of the School. “He is a leader in the transformation of our curriculum and the early adopter of educational initiatives that have improved the experience for our professional and our graduate students alike.”

Mumper received a PhD in pharmaceutical sciences and a BA in chemistry from UK. After completing a postdoctoral fellowship at the Center for Bioengineering at the University of Washington in 1992, he spent seven years in product development in the pharmaceutical and biotechnology industries, working for companies in North Carolina and Texas before returning to academia at his alma mater in 1999.

Patients with both HIV and HCV infections experience poorer health outcomes than patients who have just one infection or the other, Oramasionwu says, and one possible explanation may be that coinfected patients are underusing outpatient services. If that is true, she says, coinfected patients may not be receiving the recommended antiretroviral and antiviral medicines to the extent that patients with a single infection do.

Oramasionwu will use the development award to conduct a nationally representative study that will determine health-care use by HIV/HCV, HIV, and HCV infected patients within outpatient clinics in the United States between 2004 and 2010. The results of this pilot project will serve as preliminary data for a subsequent study in which she will evaluate treatment-related outcomes in coinfected patients as new therapies become more commonly prescribed. The preliminary data generated from this research will be used to develop an extramural grant application.

Oramasionwu is an assistant professor in the Division of Pharmaceutical Outcomes and Policy. She joined the UNC Eshelman School of Pharmacy in 2011.

This accomplishment, described in the December 13, 2012, issue of the journal Nature, may prove invaluable for developing drugs to treat many common diseases such as diabetes, high blood pressure, obesity, cancer, schizophrenia, and bipolar disorder. Such disorders are called complex diseases because each has a number of genetic and non-genetic influences that determine whether someone will develop the disease.

“In terms of the genetics of schizophrenia, we know there are likely hundreds of different genes that can influence the risk for disease and, because of that, there’s likely no single gene and no one drug target that will be useful for treating it, like other common complex diseases,” says study co-leader Bryan Roth, MD, PhD, the Michael J. Hooker Distinguished Professor of Pharmacology in the UNC School of Medicine, a professor in the Division of Chemical Biology and Medicinal Chemistry in the UNC Eshelman School of Pharmacy, and the director of the National Institute of Mental Health Psychoactive Drug Screening Program.

Roth says that drug design for complex neuropsychiatric conditions, infectious diseases, and cancer has been selectively aimed at a single molecular target in the past twenty years, but because these are complex diseases, the drugs are often ineffective and thus many never reach market.

Moreover, a drug that acts on a single targeted protein may interact with many other proteins, frequently causing toxicity and adverse effects.

“And so the realization has been that perhaps one way forward is to make drugs that hit collections of drug targets simultaneously. This paper provides a way to do that,” Roth says.

According to Roth, pharmaceutical company chemists had suggested that it was impossible to create a drug that hits multiple targets simultaneously, but “here we show how to efficiently and effectively make designer drugs that can do that.”

The new approach involves automated drug design by computer that takes advantage of large databases of drug-target interactions. The databases have been made public through Roth’s lab at UNC and through other resources.

Basically the researchers, also co-led by Andrew L. Hopkins, PhD, at the University of Dundee, used the power of computational chemistry to design drug compounds that were then synthesized by chemists, tested in experimental assays, and validated in mouse models of human diseases.

The team experimentally tested eight hundred drug-target predictions of the computationally designed compounds. Of those, 75 percent were confirmed in in-vitro experiments.

Drug-to-target engagement also was confirmed in animal models of human diseases. In a mouse model of attention deficit hyperactivity disorder, mice missing a particular dopamine receptor display distractibility and novelty seeking—recurrent aberrant behaviors similar to what is seen in ADHD. “We created a compound that was predicted to prevent those recurrent behaviors and it worked quite well,” Roth said.

The researchers then tested the compound in another mouse model where a particular enzyme for a brain neuropeptide is missing, also resulting in distractibility and novelty seeking. The drug had the same effect in those mice.

The new drug design process includes ensuring that compounds enter the brain by crossing the blood-brain barrier, which was also successfully tested in live animals.

Along with Roth, other UNC researchers among the study’s twenty-one co-authors include Vincent Setola, Xi-Ping Huang, and Maria F. Sassano. Other co-authors are from the University of Dundee, the Duke University Medical School, the Clinical Research Institute of Montreal, and the Swiss Federal Institute of Technology.

Part of the funding for the research comes from the National Institutes of Health grants supporting drug discovery receptor pharmacology.

Story courtesy of UNC Health Care

In a paper published online October 18 in the journal Angewandte Chemie, the researchers describe an experiment in which they attached an enzyme to magnetic nanoparticles, exposed them to nonheating, low-frequency magnetic fields, and observed the resulting changes in the enzymes' structure, conformation, and catalytic activity, which were different from changes induced by heating up the nanoparticles (see an animation of the experiment).

The results demonstrated for the first time magneto-mechanical effects triggered by radio-frequency magnetic fields, says Alexander "Sasha" Kabanov, PhD, the senior author on the paper and the Mescal S. Ferguson Distinguished Professor at the School. The findings, he says, could be used to create nanomedicines that will be remotely activated by low-frequency magnetic fields.

Such nanomedicines could be more efficient than therapies that use heating magnetic fields, says Kabanov, director of the School's Center for Nanotechnology in Drug Delivery. Heating magnetic fields are currently used in magnetic hyperthermia, an experimental cancer treatment that kills tumors by getting nanoparticles into the tumors and heating the particles with magnetic fields. Achieving sufficient heat requires a high concentration of nanoparticles, which Kabanov says is practically impossible via systemic administration.

"You can solve this problem with intratumoral injections, but you can't inject all tumors, especially in advanced cancers," Kabanov says. "A system based on magneto-mechanical effects, on the other hand, doesn't have that problem, and it can be activated at the right time and the right place, which will reduce the possible systemic side effects of the drug."

The paper's lead authors are Natalia L. Klyachko, PhD, an adjunct professor at the School, and Marina Sokolsky-Papkov, PhD, a research assistant professor at the School. Other authors are

• Nikorn Pothayee, PhD, a visiting research fellow at the National Institutes of Health;
• Maria V. Efremova, an undergraduate student at Moscow State University;
• Dmitry A. Guilin, a research associate at Moscow State University;
• Nipon Pothayee, a graduate student in the Macromolecular Science and Engineering Program at Virginia Polytechnic Institute and State University;
• Artem A. Kuznetsov, an undergraduate student at Moscow State University;
• Alexander G. Majouga, PhD, an associate professor at Moscow State University;
• Judy S. Riffle, PhD, a professor of organic polymer chemistry at Virginia Polytechnic Institute and State University; and
• Yuri I. Golovin, PhD, a professor and director of the Scientific and Educational Center of Nanotechnology and Nanomaterials at Derzhavin Tambov State University and a principal researcher at Moscow State University.

Learn more about Sasha Kabanov's research

A Look at the Experiment

As executive vice chair, Ferreri will manage operating budgets, oversee the division’s interaction with the School’s business cluster, and assist the division chair with duties such as annual reviews and reports and assigning course management and teaching responsibilities.

Shepherd will serve as vice chair for faculty development and mentorship. He will develop and maintain an assessment of faculty development needs in the division, create personal faculty-development plans based around needs assessment and track those plans based on outcomes. He will also create a mentoring program for the division.

“These new positions are critical to the success of PACE and the School as a whole,” says Denise Rhoney, PharmD, chair of the division. “Stefanie and Greene will be important leaders in our efforts to advance the practice of pharmacy, develop pharmacists, and engage stakeholders in accordance with the School’s Strategic Plan.”

Stefanie Ferreri

Ferreri is a clinical associate professor who has served as director of the School's community pharmacy residency program since 2004. Prior to that, she served as a residency preceptor for the program. Since 2001 she has supervised and mentored more than sixty community pharmacy residents in the program. Her research and practice interests include nonprescription medication therapy, medication therapy management, and advancing clinical practice in the community pharmacy setting.

Ferreri is an associate editor for the Handbook of Nonprescription Drugs. She has served as course coordinator for self-care and nonprescription medications since 2001 and also offers an elective in self-care therapeutics. She continues to practice in a community pharmacy providing medication therapy management regarding prescription and nonprescription medications. She also educates patients about medical conditions such as diabetes and administers immunizations. Her practice site serves as her research laboratory where she tests new services for community pharmacy practice.

On a national level, Ferreri is an active member in the American Pharmacists Association Academy of Pharmacy Practice and Management.  In 2009–2010 she served a chair of the Clinical/Pharmacotherapeutic Section. In 2008 she was awarded fellow status from the APhA, and in 2011, she received the Community Pharmacy Residency Excellence in Precepting Award. She also serves as a media adviser for this organization. Ferreri is an active member in the North Carolina Association of Pharmacists, having completed a three-year elected term as member-at-large for the board of directors in 2010.  In 2007 she received the NCAP Distinguished Young Pharmacist of the Year Award.

Greene Shepherd

Greene Shepherd, PharmD, is a clinical professor and director of professional education at the School’s Asheville satellite campus. He holds a bachelor's degree in chemistry from Appalachian State University, doctor of pharmacy from Campbell University and completed a fellowship in clinical toxicology at the University of Maryland.

Shepherd is a diplomate of the American Board of Applied Toxicology and a fellow of the American Academy of Clinical Toxicology. He is the author of more than thirty journal articles and more than twenty-five textbook chapters relating to clinical toxicology, emergency medicine, and disaster preparedness. He has developed special training courses for mass casualty decontamination for health-care workers and emergency preparedness for pharmacists. In the past he served as a professor at the University of Georgia, the director of the North Texas Poison Center, and worked as a licensed pharmacist in community and hospital sit

Established in 1975, the Watson Davis Award commemorates the memory and legacy of ASIS&T founder Watson Davis. It is given yearly to a single ASIS&T member who demonstrates outstanding continuous contributions and dedicated service to the Society.

Vaughan has been an active member of ASIS&T since 1999 and has taken on many leadership roles. She received her master’s degree in library science from the University of North Carolina at Chapel Hill.

"K.T. is an outstanding information science professional who has provided exceptional service to the ASIS&T organization," said Heather D. Pfeiffer, PhD, chair of the Watson Davis Award Jury. "She has done an incredible job of demonstrating, and continues to demonstrate, her impressive commitment to the profession of information science. It is clear that she brings a high level of dedication and quality not only to her day-to-day position that includes sharing her wealth of knowledge with students, faculty and colleagues, but also to the overall profession by working and leading multiple groups and committees…."

Vaughan chaired the ASIS&T Special Interest Group for Scientific & Technical Information Systems from 2001 to 2002. She also was a volunteer for committees such as the Constitution and Bylaws Committee from 2000 to 2007, which she served as chair from 2005 to 2007; the Leadership Development Committee from 2003 to 2011; the Annual Meeting Program Committee in 2004, 2008, 2009, and 2010. She also served as cochair of the Panels and Technical Sessions in years 2008, 2009 and 2010; and as a jury member for the 2010 Best Conference Poster session. She was director of the Special Interest Group Cabinet Steering Committee from 2007 to 2009 and from 2009 to 2011. She had been a member of this particular SIG since 2005. Most recently, Vaughan served on the ASIS&T Board of Directors for two terms (from 2007 to 2009 and again from 2009 to 2011). In the last five years she has completely revised and revamped the SIG Officer’s Manual, and reorganized both the financial system and the leadership requirements and terms for the SIGs and the SIG Cabinet. Among other changes, these required two different successful ballot initiatives to change the Society’s bylaws.

"K.T.’s generosity in sharing her leadership talents for the good of the ASIS&T organization, while demonstrating her continuous dedication as a driven member and leader through her active participation in the various programs, committees and publications, shows her superb leadership and her ability to motivate others," said Gary Marchionini, dean of the UNC School of Information and Library Science and Cary C. Boshamer Distinguished Professor. He is a former president of ASIS&T.

"She is an inspiration to all with whom she collaborates and to those she has helped educate about our profession."

Moose was named the Next Generation Pharmacist Entrepreneur of the Year and the Overall Next Generation Pharmacist of the Year. Branham received the NCPA Outstanding Adherence Educator Award, which recognizes a pharmacy educator who has made significant contributions to the education of pharmacy students in the area of medication adherence.

“These are outstanding accomplishments and a true reflection of not only Joe and Ashley, but also the standard of excellence set at Moose Pharmacies,” says Stefanie Ferreri, PharmD, director of the School’s PGY1 Community Pharmacy Residency Program, which has a residency site at Moose Pharmacies.

Moose is a fourth-generation pharmacist at Moose Pharmacies, an independent, family-owned business that has been in operation since 1882. The business has four locations around Concord, North Carolina, and Moose currently manages the Concord site.

Branham is the director of clinical services at Moose Pharmacy in Concord and a clinical pharmacist at Cabarrus Family Medicine. Branham, a former community pharmacy resident at the School, serves as preceptor to more than fifteen pharmacy students each year, and she urges all of them to become advocates for medication adherence.

“Ashley’s efforts to incorporate adherence into her teaching practices is helping to prepare tomorrow’s pharmacists to embrace their role as medication adherence experts,” says NCPA president Lonny Wilson. “By advocating the importance of medication adherence in classroom and professional settings, her commitment to this issue touches her students and the entire community.”

Led by Alexander “Sasha” Kabanov, PhD, who will direct the center, the group comprises Elena Batrakova, PhD, and a team of eighteen that includes three research faculty, postdoctoral fellows, research managers, and technicians, along with five graduate students who transferred to Carolina to continue their education. Kabanov’s group brings to UNC a research program that will receive more than $2.5 million in research funding from the National Institutes of Health over the next three years.

“Dr. Kabanov is a world leader in the delivery of pharmaceuticals and other biologically active compounds using polymers and nanomaterials,” says Bob Blouin, PharmD, dean of the School. “I am very proud and gratified that he has chosen to join us here at the UNC Eshelman School of Pharmacy.”

Sasha Kabanov, PhD

Kabanov works primarily in the areas of polymer-based drug and gene delivery, as well as biologically active polymers. He established the field of polymer genomics, which investigates the effects of polymers and nanomaterials on cellular responses to develop safe and efficient therapeutics. He is a pioneer in the use of nanotechnology to treat cancer and other diseases and is known for his discovery of a polymer that can make anticancer medications up to one thousand times more effective against drug-resistant tumors than conventional chemotherapeutic agents. He has also invented technologies that hold promise for more effective treatments of brain-related diseases such as stroke, Alzheimer’s, and Parkinson’s.

“I want to spend the rest of my career putting into practice scientific concepts in nanomedicine that I helped to create during the first half,” Kabanov says. “It is essential that the results of our work are translated to commercial products that will help people. There is no better place than UNC and Research Triangle Park to achieve that. ”

He cofounded and sits on the boards of two companies including Supratek Pharma Inc. The Pluronic-based micellar formulation of Doxorubicin, SP1049C, developed by Supratek, has successfully completed the Phase II clinical trial. It is the first polymeric micelle drug to reach the clinical stage.

After receiving his PhD from Moscow State University, Kabanov joined the faculty of the UNMC College of Pharmacy in 1994, where he established a research program that would grow into a nanomedicine group with more than thirty faculty. He was named the Parke-Davis professor and director of the UNMC nanomedicine center in 2004. Kabanov is the author of more than 220 peer-reviewed papers and sixteen book chapters. He is named as an inventor or co-inventor on twenty-six U.S. patents and more than one hundred patents worldwide. In 2010 he became the first chemist awarded a $4.5 million “megagrant” by the Russian government to open laboratory of Chemical Design of Bionanomaterials, of which he is a director, at Moscow State.

He joins the School as the Mescal Swaim Distinguished Professor in the Division of Molecular Pharmaceutics and is also named a codirector of the Carolina Institute for Nanomedicine in addition to directing the CNDD.

“I look forward to new creative collaborations in science and education both within and outside of the School,” Kabanov says, “Collectively we have the best nanomedicine team in the world here at UNC.”

Elena Batrakova, PhD

Batrakova also received her PhD from Moscow State and was one of the first trainees in Kabanov’s UNMC lab in 1995. She was named a research associate professor at Nebraska in 2010. She joins the School as an associate professor in MOPH and a as member of the CNDD.

“It has been less than three months my lab has joined UNC,” she says, “But we are already feeling the strong support from the School and the University. It’s amazing how much time, energy, and effort was dedicated to make our transition smooth and fast. I think we are fortunate to work at such wonderful place.”

With NIH support, Batrakova is developing cell-mediated delivery of therapeutic polypeptides to the brain for treatment of Parkinson's disease using inflammatory-response cells, monocytes and macrophages, as vehicles. She is also devoted to development of a new drug delivery polymer-based system of chemotherapy to treat multidrug-resistant tumors, and central nervous system disorders. Batrakova is the author of nearly eighty peer-reviewed publications and six books chapters and holds ten patents.

Bryan Roth, PhD, MD, a Michael Hooker Distinguished Professor in the UNC School of Medicine and the pharmacy school, is one of the lead investigators on the grant. Jian Jin, PhD, an associate professor and the associate director of medicinal chemistry at the pharmacy school’s Center for Integrative Chemical Biology and Drug Discovery, is the principal investigator for one of the projects supported by the grant.

Jin’s lab will receive $1.15 million in direct cost to create clinical candidates for treating schizophrenia and other mental disorders. In 2011, researchers led by Jin and Roth discovered three first-in-class chemical compounds that have an unprecedented mechanism of action. Jin will use the new grant to develop those compounds into clinical candidates, which could ultimately lead to safer, more effective medications for those conditions.

The other lead investigator on the grant is Marc Caron, PhD, the James B. Duke Professor of Cell Biology at the Duke University School of Medicine. The other investigators include William Wetsel, PhD, an associate professor of psychiatry at Duke University; and Doug Johnson, PhD, and Chris Schmidt, PhD, of Pfizer. Schmidt is senior director at Pfizer Global Research and Development, while Johnson is an associate research fellow at Pfizer Worldwide Research and Development.

The team’s findings are published in the June 27 issue of Angewandte Chemie.

“Imagine that you have an inhibitor that is inert but can be made active by light,” says David Lawrence, PhD, senior author of the study. “It is slowly taken up by the cell and floats around everywhere. Light allows you to switch that inhibitor on instantaneously. And by focusing the light on one area of the cell, you can activate the inhibitor only in that area.” (See a video of the technique)

The technique described in the article uses three wavelengths of light to activate different bioreagents in the same cell, offering a high degree of temporal and spatial resolution that one would not get with a conventional inhibitor, enzyme, or sensor, Lawrence says. The process could be used as a tool to study signaling pathways, which are incredibly complex, fast acting, and localized to different areas within cells, he says.

Light at a long wavelength could switch on an enzyme, followed by light of a shorter wavelength activating a sensor to detect the activity of the enzyme, Lawrence says, while an even shorter wavelength to turn on an inhibitor to block the action of the enzyme, although he adds that nothing this sophisticated has yet been done.

“Basically, we have a way to communicate with a bioreagent once it’s in the cell. It’s like a remote control: we can press a button and say, ‘We want you to be active right here, right now.’”

Lawrence is a Fred Eshelman Distinguished Professor and chair of the School’s Division of Chemical Biology and Medicinal Chemistry. His coauthors on the paper are Melanie Priestman, PhD, and Thomas Shell, PhD, of UNC-Chapel Hill; Liang Sun, PhD, of Pharmaron-Beijing BDA; and Hsien-Ming Lee, PhD, of Academia Sinica, Taiwan.

VIDEO: Selectively Activating Bioreagents with Photolysis

Frye is the director of the School’s Center for Integrative Chemical Biology and Drug Discovery, a research group bringing dedicated medicinal chemistry expertise to bear on biological targets of therapeutic relevance that are under investigation by UNC faculty. CIBDD project teams work with other groups on the UNC-Chapel Hill campus to move potential drug targets through the drug discovery and development process.

“The Eshelman professorships support outstanding scholars and researchers like Dr. Frye who are working at the forefront of the pharmaceutical sciences,” says Bob Blouin, PharmD, dean of the School and Vaughn and Nancy Bryson Distinguished Professor. “This award is well-deserved recognition of the impressive contribution he has made to the School, the University, and to the advancement of cancer research here at Carolina.”

The Fred Eshelman Fund for Distinguished Professors was created in 2003 by Fred Eshelman, PharmD, and is held as an endowment by the Pharmacy Foundation of North Carolina. Other holders of $1 million Eshelman Distinguished Professorships are Leaf Huang, PhD; Mike Jay, PhD; David Lawrence, PhD; Howard McLeod, PharmD; and Xiao Xiao, PhD. The professorship provides $50,000 a year to support a faculty member’s research program.

Frye joined the School’s Division of Chemical Biology and Medicinal Chemistry in 2007 after a twenty-year career with GlaxoSmithKline. He is co-inventor of GSK’s Avodart, a drug used to shrink an enlarged prostate gland that is also under study for prevention of prostate cancer. He also established and led the department at GSK’s Research Triangle Park facility that discovered the compounds that became the breast-cancer drug Tykerb and Votrient, a drug used to treat renal cell carcinoma.

In 2008, the NCI designated Frye’s center and UNC’s Lineberger Comprehensive Cancer Center to be a Comprehensive Chemical Biology Center, and three contracts to advance drug discovery for pediatric acute lymphoblastic leukemia, glioblastoma, and renal cell carcinoma have been awarded. These contracts are bringing more than $5.5 million to UNC to discover new medicines to treat cancer. Frye has also established a program in the chemical biology of epigenetics supported by an NIH R01 grant.

The findings, published in the July 25 issue of the leading scientific journal Nature, provide proof of concept for a new approach in the effort to cure AIDS. Researchers believe that a major reason why HIV infection reemerges after patients stop taking their medication is the existence of persistent reservoirs of dormant virus in the immune system that are not attacked by anti-AIDS drugs. Disrupting and clearing these reservoirs are critical to finding a cure for AIDS.

“This work provides compelling evidence for a new strategy to directly attack and eradicate latent HIV infection," says David Margolis, MD, a professor at the UNC School of Medicine who led the study.

“Long-term, widespread use of antiretrovirals has personal and public health consequences, including side effects, financial costs, and community resistance. We must seek other ways to end the epidemic, and this research provides new hope for a strategy to eradicate HIV completely from the body.” (Infographic on the science behind this new strategy)

Researchers at UNC, in collaboration with scientists from the Harvard School of Public Health, National Cancer Institute, Merck, and the University of California at San Diego, conducted a series of experiments to evaluate the potential of the drug vorinostat to activate and disrupt the dormant virus. Vorinostat is a deacetylase inhibitor used to treat some types of lymphoma.

Initial laboratory experiments showed that vorinostat unmasked the hidden virus in CD4+ T cells, specialized white blood cells that the virus uses to replicate. Researchers then administered vorinostat to eight HIV-infected men who were medically stable on antiretroviral therapy. The levels of active HIV virus were then measured and compared to the levels before administration.

The patients receiving vorinostat showed an average 4.5-fold increase in the levels of HIV RNA in CD4+ T cells, evidence that the virus was being unmasked. This is the first published study to show the potential for deacetylase inhibitors to attack latency within dormant virus pools in a translational clinical study.

Kashuba, a professor in the School's Division of Pharmacotherapy and Experimental Therapeutics, says the results pave the way for researchers to look for other deacetylase inhibitors that work in a similar fashion but are safer and more effective.

“Vorinostat is associated with a number of serious side effects, so it may not be an ideal drug to use chronically in HIV-infected patients,” says Kashuba, whose lab conducted pharmacokinetic monitoring on the study volunteers to ensure they received safe and effective doses and to pinpoint the optimal time to collect their blood cells.

“However, vorinostat provides us with a starting point in understanding the relationship between drug exposure in the body and how virus is released in the cells. We now know that this is a viable target in people, and we can search for more potent and safer drugs to move into clinical studies.”

Funding for the research was provided by the National Institutes of Health, Merck & Co., and the James B. Pendleton Charitable Trust. Early results of this study were first presented and reported in March 2012 at the Conference on Retroviruses and Opportunistic Infections in Seattle, Washington.

The research conducted is part of a UNC-led consortium, the Collaboratory of AIDS Researchers for Eradication, funded by the National Institute of Allergy and Infectious Diseases. The consortium is administered by the North Carolina Translational and Clinical Sciences Institute at UNC, one of sixty medical research institutions in the United States working to improve biomedical research through the NIH Clinical and Translational Science Awards program.

The botanical product silymarin, an extract of milk thistle commonly used by some patients with chronic liver disease, did not provide greater benefit than a placebo for patients with treatment-resistant chronic hepatitis C virus infection, according to a study by UNC scientists published in the July 18 issue of the Journal of the American Medical Association.

Chronic hepatitis C virus infection, or HCV, affects almost 3 percent of the global population and may lead to cirrhosis, liver failure, and liver cancer. A large proportion of patients do not respond to certain treatments for this infection, and many others cannot be treated because of co-existing illnesses. “Thus, alternative medications with disease-modifying activity may be of benefit,” according to background information in the article. Thirty-three percent of patients with chronic HCV infection and cirrhosis reported current or past use of silymarin for the treatment of their disease. Clinical studies that have evaluated milk thistle for a variety of liver diseases have yielded inconsistent results.

“This was the largest and most robust randomized placebo-controlled clinical trial ever conducted with silymarin in patients with chronic HCV infection,” says Roy Hawke, PharmD, PhD, a clinical assistant professor at the UNC Eshelman School of Pharmacy and one of the study’s coauthors. “Therefore, patients should re-evaluate their use of silymarin in light of the overwhelming evidence for its lack of clinical benefits in this study, and the recent availability of new direct-acting antivirals that have been shown to be highly effective.”

Michael W. Fried, MD, a professor in the UNC School of Medicine conducted the study along with Hawke and other colleagues in order to assess the use of silymarin for treating chronic HCV infection. The multicenter, placebo-controlled trial was conducted at four medical centers in the United States over three years. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (an enzyme that reflects liver function known as ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered three times per day for twenty-four weeks. The primary outcome measure for the study was a serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50 percent decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.

At the end of treatment, only two participants in each treatment group achieved the prespecified primary end point. The percentages of participants who achieved the primary end point were 3.8 percent in the placebo group, 4.0 percent in the 420-mg silymarin group, and 3.8 percent in the 700-mg silymarin group. The researchers also found that there was no statistically significant difference across treatment groups when changes in serum ALT levels from the beginning of the study to end of treatment were analyzed. Also, average serum HCV RNA levels did not change significantly during the twenty-four weeks of therapy.

There were no significant changes in physical or mental health components of quality-of-life scores, in chronic liver disease health-related quality-of-life assessments, or in depression scores in any group. Frequency of adverse events reported by individual patients also did not differ significantly among the treatment groups.

“In summary, oral silymarin, used at higher than customary doses, did not significantly alter biochemical or virological markers of disease activity in patients with chronic HCV infection who had prior treatment with interferon-based regimens,” the authors conclude.