Lab Offers Hope for Kids with Cancer
Wilmington, Delaware
Monday, August 24, 2009 @ 11:27 AM EDT
by: Wilmington News Journal (8/24/09)
Several boxes sit inside a refrigerated room in a Rockland laboratory, packed with a total of about 100,000 chemical compounds. One of them may someday hold the key to a child's recovery from cancer.
The lab is part of the Nemours Center for Childhood Cancer Research, a fledgling enterprise that recently hired researcher Andrew Napper to launch a drug discovery program for childhood cancers.
Napper, who comes to Nemours by way of the University of Pennsylvania and a 16-year career with biopharmaceutical companies, is assembling a high-throughput screening lab -- a research method that combines biological analysis, robotics and data processing to rapidly test the potential of thousands of compounds to disrupt the activity of cancer cells.
"It essentially is like a lock and a key, literally," Napper said. "The chances are that more than one key will fit in a lock. We just don't know which ones."
Napper hopes to find cancer treatments that don't cause the same harsh side effects on children as the cancer drugs used in adults.
The new effort illustrates the growing role universities and research institutes are playing in discovering new drugs, a painstaking process that leads to far more failures than successes. Technological and scientific advances have expanded the capabilities of academic researchers, who have more flexibility than their private sector counterparts to pursue research without commercial considerations.
At the Nemours childhood cancer center, which was established in January 2008, research is focused on three areas: finding biomarkers, or biological characteristics that mark the presence or progression of a cancer, exploring new drug delivery methods and, now, searching for new drugs.
"In childhood cancer, people don't do much to discover drugs for children because it's not very profitable," said Ayyappan Rajasekaran, the research center's director.
Rajasekaran, who came to Nemours in 2007 from the University of California, Los Angeles, said Napper's lab will represent the first academic drug discovery facility in Delaware.
"He is really one of the best in the country," Rajasekaran said. "His expertise in the field is enormous."
Napper, 48, a native of England, was the director of high-throughput screening at the Penn Center for Molecular Discovery from 2005 until earlier this year, when he came to Nemours.
Prior to arriving at Penn, Napper conducted drug discovery research at several biopharmaceutical companies in the Boston area, including Genzyme Corp., one of the world's biggest biotech firms. His work was largely focused on cancer and infectious diseases.
When Napper, a University of Oxford and Penn State-trained chemist, started in the biotech industry, high-throughput screening was a technique used almost exclusively in an industry setting.
Since then, he said, several changes have occurred. The technology has progressed to make equipment more affordable, accessible and compact. And scientific advances in the area of genomics have helped create hundreds of new biological targets, fueling a demand among researchers to conduct high-throughput screening experiments. As a result, high-throughput screening labs have started to proliferate in academic institutions, largely in the last five years.
"There's definitely been a shift," Napper said. "Drug discovery is no longer exclusively the preserve of the large, vertically integrated organizations."
One such organization sits within throwing distance of the Nemours research center. AstraZeneca, the global drug maker with U.S. headquarters and research facilities in Fairfax, has inked a number of deals in recent years with universities and research groups.
"There's a growing awareness that we need to work more closely with academia," said Alan Cross, chief scientist in the area of neuroscience for AstraZeneca. "I think it stems from understanding that we can't do everything ourselves."
Some of the partnerships focus on fundamental research -- understanding the mechanisms of certain diseases and illnesses, and how they may be treated. But increasingly, AstraZeneca is seeking out collaborations that will bring the company new compounds and drug targets, Cross said. For example, earlier this year, AstraZeneca licensed a portfolio of chemical compounds -- a potential new type of antidepressant -- from the Mayo Clinic and Virginia Tech.
"This is very much a new area for academia," Cross said.
AstraZeneca operates its own automated high-throughput screening lab at its Fairfax research campus. Napper's lab, which the researcher is building basically from scratch, will be on a smaller scale. Napper, who is in the process of ordering lab equipment and compound libraries, said he wants to create a flexible setup so researchers can move quickly between experiments.
The high-throughput screening method begins with a microplate with hundreds of tiny wells, each holding a test compound. A biological target is introduced to the chemical compounds to test the interaction between the two entities, with automated equipment tracking properties including fluorescence and luminescence. The results are recorded in a computer database.
Promising compounds would be explored further in cell-based tests, followed by tests in animals and, the researchers hope, clinical trials in humans.
Napper said the lab is more than a $1 million investment, including at least $500,000 in equipment costs. The research center was aided in part by a $250,000 grant from the Andrew McDonough B+ Foundation, a local organization founded in honor of its namesake, a 14-year-old Wilmington boy who died in 2007 after a battle with leukemia and sepsis.
In part because of the foundation's donation, a major focus of Napper's work will be childhood leukemia, a term for several types of cancer of the blood or bone marrow.
There are two major types of leukemia that occur in children. Acute lymphoblastic leukemia, or ALL, has a cure rate of about 80 percent, while acute myelogenous leukemia, or AML, has a cure rate of about 50 percent.
Children stricken with leukemia are treated with the same drugs used in adults -- powerful chemicals that kill cancerous cells but also healthy cells, which can lead to harsh side effects and developmental problems in children.
Researchers at Nemours have a goal of reaching a 100 percent cure rate with minimal side effects for children. Napper said one of the things that drew him to the health system was the strong interaction between researchers and physicians, with the goal of conducting "translational research" -- advancing research discoveries from the lab to clinical practice.
And Napper can always walk across the street to Nemours' Alfred I. duPont Hospital for Children to remind himself of the importance of his work.
"I really like to see the research directed with such a clear goal," he said.
modified: Monday, August 24, 2009 @ 01:04 PM EDT
created: Monday, August 24, 2009 @ 11:32 AM EDT
About Nemours
Nemours, one of the nation’s largest pediatric health systems, is dedicated to achieving higher standards in children’s health. Nemours offers an integrated spectrum of clinical treatment coupled with research, advocacy, and educational health and prevention services extending to all families in the communities it serves. Starting with Alfred I. duPont’s bequest over seventy years ago, Nemours has grown into a multi-dimensional organization offering personalized clinical and preventive care focused on children.
Nemours owns and operates the Alfred I. duPont Hospital for Children in Wilmington, Delaware and major children’s specialty clinics in Delaware (Wilmington), Florida (Jacksonville, Orlando and Pensacola), Pennsylvania (Philadelphia and Bryn Mawr) and New Jersey (Atlantic City and Voorhees). Having recently received preliminary approval from the State of Florida, Nemours will establish a new full-service children’s hospital as part of an integrated pediatric health campus in Orlando. KidsHealth.org, the world’s most visited pediatric health care Web site for parents, kids and teens, is a project of Nemours.
Nemours employs over 4,400 individuals, including 430 pediatric physicians, specialists and surgeons who cared for approximately a quarter of a million children in 2007. The organization’s goal is to align with parents, physicians, community leaders, children’s advocates and elected officials to ensure optimal wellness for every child. Additional information about Nemours can be found at www.nemours.org.
