Research answers AMD questions, creates economic development opportunity

Portrait: Gre Hageman, PhD

Making a tangible difference in the well-being of people has always been the main goal for Greg Hageman, PhD, professor of ophthalmology and visual sciences in the UI Carver College of Medicine. Becoming a businessman who is starting a company from the ground up is something he had never considered, or imagined.

He began his career as a marine biologist after graduating with a PhD in biology from the University of Southern California in 1983. His early research interests were focused on retinal cell biology, but as he began to learn more about severe blinding disorders in humans, especially age-related macular degeneration (AMD), he reconsidered his career direction.

“I decided to change because I hoped to make a contribution through the clinical side of medicine,” said Hageman. He came to the College in 1997 and has been studying AMD since 1988.

Abnormal deposits called drusen that lie beneath the retina of diseased eyes initially captured his attention. He wondered why science did not have an explanation about what the deposits were or how they affected sight. When no animal model was found to have drusen deposits, he began looking at human eyes from tissue donors.

“Currently, we work with a repository comprised of about 3,500 pairs of donor eyes,” said Hageman. “We couldn't have reached this point in our research or made the various discoveries without access to them.”

Long, slow, methodical research over the next several years gave way to a major discovery in 2001 that showed that variations in the factor H gene, a gene that regulates inflammation, increased the likelihood that an older person might develop the disease. Since then, he has been continuously working with collaborators on research to show that variations in a second gene, factor B, also contributes to AMD risk.

Hageman and his colleagues at the UI, Columbia University Medical Center and the National Cancer Institute (NCI), along with several other institutions, showed that these two genes accounted for nearly three out of four cases of AMD. The first and most recent discoveries have the potential to help thousands of individuals.

Assisted by a five-year, $14.6 million National Institutes of Health (NIH) grant awarded in August, the team has begun a series of investigations to learn more about the genes' roles in the immune system. The researchers believe variations of complement factor H and factor B in these two genes somehow alter the function of a key pathway in the immune system, which they suspect leads to AMD. The factor H gene also is linked to similar eye problems associated with membranoproliferative glomerulonephritis type II (MPGN II), a rare kidney disease.

The scientists will explore how gene variations affect the function of the factor H protein and explore the idea that replacing, augmenting or removing the malfunctioning protein can delay or even prevent the eye disease caused by AMD and MPGN II.

“For the first time, we have strong data on which to base the next phases of research. We're excited that the NIH grant will allow us to explore and advance our ideas related to the role of these genes in the disease process,” said Hageman. “The grant also has a required business component to it. We're in the process of creating a company that will seek to develop diagnostic tools and therapies for AMD.”

The investigation also includes efforts to determine whether additional genes are associated with AMD and whether other inflammation-based diseases, such as Alzheimer's disease, are caused by dysfunction of the same or related pathways. Additional aims involve studying the biology of the eye's complement system to determine whether proteins and markers other than a vision test, can reveal vision decline.

“Our research requires a multidisciplinary team capable of approaching this challenge from many different angles. I'm enthusiastically looking forward to working with my co-investigators, all of whom share the overall dream of ultimately developing therapies for this devastating disease,” added Hageman.

Beyond the research, Hageman is actively pursuing the challenge of taking the scientific discoveries and creating a business. With no formal business training, this has proven an interesting and challenging project.

“When the data linking the genes to the disease came out, it hit hard,” said Hageman. “It was not uncommon to receive 10 to 20 calls a day from businesses and venture capitalists. It was difficult to deal with the volume.”

Hageman began talking with David Scheer, a company builder, and Colin Foster, a pharmaceutical industry executive, and found that they were interested in focusing on AMD treatments as well. “I felt I could make my best contributions and biggest impact by forming a business with these individuals.” Foster has been selected to serve as chief executive officer of the new company, Optherion, Inc.

As the plans began to come together, Hageman became convinced that he would have to leave Iowa, especially since Optherion was taking shape on the East Coast. 

“Things changed abruptly following a meeting with Meredith Hay, PhD, UI vice president of research, to tell her I was leaving,” said Hageman. “She said to me, ‘why don't you just do it here, we can make it happen.' She has never wavered in that decision.”

With the support of the administration, space has been committed for his academic research and the research and development component of Optherion on the Oakdale campus. Members of the State of Iowa, Board of Regents also have been supportive. Since a portion of the company could stay in Iowa, it allowed Hageman to stay too.

“Dr. Hageman's research is very promising and crucial to advancing treatment for this debilitating disease,” said Hay. “I am committed to doing everything possible to enable University of Iowa researchers, like Dr. Hageman, to advance and translate their discoveries to new cures and therapies for patients. This particular project is very exciting and was one I have supported from the beginning.”

Since last spring, Hageman has been learning the ins and outs of entrepreneurship. From one of the most critical pieces of creating a new company—acquiring venture capital—to items of seemingly small importance, such as deciding where the door locks are positioned or what color the carpet will be, he's found it all a learning experience.

Hageman has enjoyed stepping out of his long-standing role as a researcher, even if only on a temporary basis. Recently, he's found himself traveling to venture capital meetings, a slight switch from his usual attendance at the annual meetings of the Association for Research in Vision and Ophthalmology or the American Society of Cell Biology.

“It's been great fun and exciting. As with anything new, there are challenges and commitment of immense amounts of time,” he explained.

Hageman and his colleagues hope to have Optherion up and running by Jan. 1, 2007, creating approximately 35 jobs for the area. In the meantime, he says he's working to his maximum ability—18-20 hour days, 7 days a week. 

“It's staggering to think of all the people who have touched this research program,” said Hageman. “We've come so far as a team, and I've had such wonderful support within the University. I'm looking forward to things to come.”