Temple Magazine

Boosting Big Pharma

The Moulder Center for Drug Discovery Research provides the pharmaceutical industry with a much-needed shot in the arm.

Story by Preston M. Moretz, SCT ’82

Compared to the recent rocky roads of other U.S. industries—such as the automotive industry—the field of prescription drugs might appear to be holding its own: The IMS Institute for Healthcare Informatics reported its total 2010 sales to be more than $307 billion.

What that number does not reveal is that big pharma suffers from an “innovation gap,” the amount of products—or rather, lack thereof— coming through the industry pipeline.

In 1996, the industry hit its peak, with 56 new drugs approved for consumer use by the U.S. Food and Drug Administration. Since then, new drug approvals have steadily declined to as few as 18 per year.

But a decline of internal resources that have cost the industry more than 300,000 jobs over the past decade are affecting the number of products in development. Thus, the innovation gap—and potentially, a dearth of treatments for those battling some of the world’s most confounding illnesses, including Alzheimer’s disease, cancer and AIDS.

Now, big pharma is rethinking its R&D strategy and its business model. It is turning to small biotechnology companies and academic institutions with drug discovery centers—such as Temple—to supplement declining R&D resources.

First in the Region

At Temple, the Moulder Center for Drug Discovery Research helps close the innovation gap. By combining industry expertise with the exploratory spirit of academia—where risks do not depend only on economics—Moulder scientists research new treatments and prepare them for clinical human trials conducted by large pharmaceutical companies.

Magid Abou-Gharbia, director of the Moulder Center, embodies that mixture of industry and scholarship. With 26 years at Wyeth Pharmaceuticals and 350 worldwide patents under his belt, Abou-Gharbia arrived at Temple in 2008 ready to alter the course of the region’s pharmaceutical industry.

According to the organization Pennsylvania Bio, one in six jobs and 15 percent of the economic activity in greater Philadelphia can be traced to the pharmaceutical and life sciences industries. But the Moulder Center is the first fully integrated academic drug discovery center in the Philadelphia region, which is home to so many pharmaceutical companies that it often is considered the “Silicon Valley” of biomedical research and drug discovery.

“Given the economy and all of the industry’s mergers and acquisitions, the internal resources of pharmaceutical companies have been reduced substantially— they don’t have all the talent they need,” Abou-Gharbia says. “Pharma is no longer attempting certain drug discovery projects because success isn’t guaranteed. But they are finding that we in academia have much more freedom to take on higher-risk projects.”

The Moulder Center’s pursuit of higher-risk projects also will improve the health of millions of medical patients.

“There are diseases that are highly risky to pursue, have less than 200,000 patients, affect low-income populations and are not considered prevalent,” Abou-Gharbia says. “Pharma is not pursuing drugs for them because of economics. But such drugs are being sought through academic drug discovery centers.”

Since Lonnie, PHR ’80, and Sharon, PHR ’80, Moulder established the Moulder Center in the School of Pharmacy in 2008, Abou-Gharbia has overseen its rapid growth. What started as a nearly one-man show now is staffed by 12 experienced drug discovery scientists and is developing local, national and international drug discovery research collaborations almost monthly.

For example, Moulder Center researchers are working with Cureveda, a biotech company founded by Johns Hopkins University researchers, on the treatment of a wide range of oxidative stress-related diseases, including diabetic neuropathy, cardiovascular disease and cancer. This past summer, the center joined forces with Cortendo—a Sweden-based pharmaceutical company—to target metabolic syndrome, a combination of medical disorders that, when occurring together, increase the risk of cardiovascular disease and diabetes.

In collaboration with the University of Rochester Medical Center in New York, they are fighting several diseases, including bacteria resistance, a persistent threat to the medical community that affects more than two million patients annually.

Magid Abou-Gharbia, director of the Moulder Center for Drug Discovery Research, holds more than 350 worldwide patents. Photo courtesy Joseph V. Labolito.

“Infection and bacteria resistance to treatment is a major problem in hospitals,” Abou-Gharbia says. “Many people survive surgery only to succumb to a post-op infection. We’re working with infectious disease biologists to develop drugs that will combat this.”

Collaborating for the Future

The center mainly focuses on identifying biological targets, proteins, enzymes or chemicals in the body that when imbalanced, inhibited or overactivated, can cause disease. For example, when a person’s level of the chemical serotonin becomes imbalanced in the brain, he or she suffers from depression. The drug Effexor, developed by Abou-Gharbia at Wyeth, treats depression by restoring serotonin to its proper level.

The number of potential targets has risen over the past 11 years. Since the human genome was deciphered in 2000, biomedical researchers have identified close to 5,000 new genes which could be drugable biological targets if they are found to be the cause of certain diseases. This increases the chances for myriad new drugs and therapies, many for diseases for which there are no or limited treatments. In today’s marketplace, fewer than 350 biological targets are addressed by 1,500 drugs.

“Once we in academia correlate these new genes to specific diseases, we can partner with pharma to develop potential new therapies,” Abou-Gharbia says. “For example, when you look at cancer and some of the gene mutations that were found, cancer drugs and therapies were able to be developed because researchers could connect those genes and mutations to the disease.”

After a biological target is determined to be the cause of a disease, Moulder Center researchers work to identify molecules that will interact with the target and alter its activity. When such molecules are found, the researchers generate compounds that affect the target successfully, and then test the new drug in the lab to determine its suitability for clinical testing in humans. If the drug passes, high-quality samples are produced for human testing by a partnering pharmaceutical company.

According to Abou-Gharbia, over the next several years, the Moulder Center will work toward developing lead molecules that effectively fight diseases such as Alzheimer’s, AIDS and cancer. Temple researchers will prepare the compounds for testing, readying them for a midsize or multinational pharmaceutical company to develop them into drugs.

“Because academic drug discovery centers like Moulder are discovering tomorrow’s drugs by combining the innovation of academia with the resources of industry, people will have access to new and better drugs,” Abou-Gharbia says. “That’s the way of the future.”

Preston M. Moretz, SCT ’82, is a staff writer in University Communications at Temple.

Joint Efforts

The Moulder Center supports approximately one dozen Temple researchers on projects, including:

Rodrigo Andrade, assistant professor of chemistry in the College of Science and Technology, whose molecules the center uses to explore cancer and antibacterial activity.

Mark Feitelson, professor of biology in the College of Science and Technology, who is working on new therapies for the hepatitis B virus.

Salim Merali, associate professor of biochemistry at the Fels Institute for Cancer Research and Molecular Biology in the School of Medicine, who is working on identifying compounds that inhibit the proliferation of prostate cancer cells.

Domenico Praticò, associate professor of pharmacology in the School of Medicine, who studies Alzheimer’s disease.

 

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