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.

“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.