Genomics could boost molecular imaging to new heights

October 31, 2001

The human genome may provide keys to unlocking the potential of molecular imaging. By decoding genetic blueprints, the mechanisms underlying disease might be better understood. Molecular markers sensitive to the earliest processes of diseases might,

The human genome may provide keys to unlocking the potential of molecular imaging. By decoding genetic blueprints, the mechanisms underlying disease might be better understood. Molecular markers sensitive to the earliest processes of diseases might, therefore, be integrated into imaging agents. If pharmaceutical companies can develop therapeutic agents that counter the disease mechanism, the onset of disease might be delayed for years, perhaps indefinitely.

This is the foundation for the deal GE Medical Systems cut with GlaxoSmithKline in August (SCAN 9/5/01). But there is far more at stake than a single collaboration. And more imaging vendors are getting involved in this area than just GE. Months before the GSK deal was announced, GE established a business unit dedicated to this evolving area of imaging.

“We see genomics creating a 10-fold increase in disease targets,” said Eric Stahre, general manager of genomics and molecular imaging. “And because there are going to be therapies for those targets, you are going to need more specific diagnostics-and those will be coming out in molecular imaging.”

GE workers dedicated to the effort number only in the “dozens,” said Stahre, who refused to give a more exact headcount, citing competitive issues. His staff can do the job, he said, because they can draw from and apply the talents of personnel assigned to other parts of GE Medical Systems and its parent, General Electric.

“This is really a multidisciplinary approach to developing the next generation of molecular imaging,” Stahre said. “It is cross-modality and it also taps into the work of the thousands of folks at CR&D (corporate research and development). And it involves disciplines we do not traditionally work with. For example, we have molecular biologists and biochemists on the team.”

GE is not the only vendor that sees promise in the human genome. Philips Medical Systems is working with a number of leading academic institutions to determine how imaging might help scientists understand gene expression in disease, according to Allen Paul Smit, Philips vice president for strategy and business development.

“There are very exciting opportunities in gene therapy, in understanding how people inherit disease and what we can do to find it in time and monitor therapy,” Smit said. “You will see us unfold our strategy in the next couple of years.”

But rather than focusing on academic institutions, GE is emphasizing private industry. Pharmaceutical companies are especially attractive.

“There’s a natural synergy in us working together and in their putting money into that (diagnostic) direction, because it helps with their drug and drug delivery development,” said Joseph Hogan, president and CEO of GE Medical Systems.

The collaborative research agreement between GE and GSK is designed to integrate molecular imaging technologies and pharmaceutical development. Molecular imaging may facilitate the discovery process, illuminating the body locations and order in which disease mechanisms are activated. They could be critical in the therapy-testing phase, when physicians must identify test subjects for clinical trials and follow the effect of the therapies on these patients. Molecular imaging could have its greatest impact when the therapies enter the clinical mainstream, screening high-risk patients for early signs of disease, monitoring patient response to allow physicians to tailor the regimen, and following the patient for signs of recurrence or some other change in condition.

GE’s first corporate alliance was on the fringes of the pharmaceutical industry. The collaboration with Woodlands, TX-based Genometrix announced last spring was to focus on combining MRI with microarray technologies tuned in to genetic indicators of disease. Patients would be screened for preclinical signs of disease using genetic tests developed by Genometrix. They would then be clinically assessed using MRI and MR spectroscopy. The venture ran into a snag, however, when financial problems surfaced at Genometrix and the company suspended business operations.

“The good news is that we got out of the alliance exactly what we wanted and that is some sharing of intellectual property,” said GE spokesperson Patrick Jarvis.

The GSK deal is more expansive and holds far greater promise. The collaborative team, comprising researchers from GSK, GE, and academia, is looking for markers of biological changes that indicate the future development of chronic obstructive pulmonary disease (COPD), which the American Lung Association believes could become the third leading worldwide cause of death by 2020. The collaboration is part of a coordinated exploration of possibilities.

“We have in place an umbrella agreement with GlaxoSmithKline that allows us to explore a number of different areas,” Stahre said. “So you will see more developments along these lines.”

GE is exploring new ground and, therefore, treading carefully. MR spectroscopy and PET barely hint at the possibilities, Stahre said. The key to the future is finding out how to build on these offshoots of conventional imaging.

“We have to decide how we can transform what we do today diagnostically into what can be accomplished tomorrow with genomics and proteomics (the science of protein expression and interaction),” he said. “Our short-term objectives are to take those first steps, test the waters, and look at adjacent markets to figure out what we really need to do to create the next generation of diagnostic capability.”

Collaborations with pharmaceutical companies are seen as the way to accomplish this. R&D staff at these firms are heavily focused on the development of therapeutics, while GE wants to focus on the diagnostics side.

“If we know which molecular therapeutics are getting ready to come out of the pipeline, we can make sure we have the diagnostics to go with them when they are brought to market,” Stahre said.

CT will lead the charge for GE’s newest initiative. The modality will be a prime source of information regarding COPD, the first project under the collaborative agreement with GSK. This disease is especially suited to the two companies because GlaxoSmithKline has particular expertise in respiratory disease, and GE has the technological capability, in multislice CT, to characterize COPD.

“Clearly, having an early diagnostic capability for COPD would play very well for our CT business,” Stahre said. “When (practical results) become a reality, they will go right into the CT product mix and out the door as a CT package.”

This diagnostic capability will probably involve some high-powered computing, not only on the scanner but plugged into the information technology supporting the diagnostic process at clinical institutions as well. GE has put together a research team at its CR&D facility in Schenectady, NY, to examine how “bioinformatics” will figure into the future of molecular imaging.

“It is clear that we will need advanced image analysis capabilities and it is also clear that we will have to look at data outside our normal diagnostic imaging space,” Stahre said.

The company is further leveraging expertise available at its Schenectady center as part of the initial research addressing COPD. CR&D specialists in molecular biology, chemistry, and imaging physics and engineering are collaborating with researchers at GlaxoSmithKline and academicians working within GSK’s COPD Clinical Network. This international network includes facilities in Spain, Italy, the U.K., Canada, Denmark, the Netherlands, and the U.S. The academic centers making up this network are trying to identify the genes that make patients susceptible to COPD. These genes are associated with higher risk of developing the disease, but their presence alone is not enough to cause it. Other factors must be present as well.

COPD is only the first of several projects that may be conducted with GSK, which is already exploring the genetic roots of several other conditions. These include asthma, early-onset heart disease, osteoarthritis, depression, and metabolic syndrome (characterized by the clustering of risk factors including obesity, high blood pressure, insulin resistance, and dyslipidemia). And GE is already hatching plans to extend its collaborations to include companies other than GSK.

“This is definitely just the beginning,” Hogan said. “As we tap into (pharmaceutical) companies, it opens up a whole new world. We can understand from the inside what they think and what they see.”

These collaborations promise to serve as a catalyst for the evolution of molecular imaging, which until now had constituted little more than a rebranding of such existing technologies as PET and MR spectroscopy. GE executives hope corporate collaborations will boost the company’s understanding of how genomics might be used to develop novel and advanced molecular imaging probes. This in turn may serve as the basis for identifying future corporate acquisitions.

“We grow organically so that we can make good decisions about what we want to acquire,” Hogan said. “We want to identify ongoing businesses that will allow us to extend our capability in certain areas more rapidly and efficiently than we can do internally. It’s all about cost and time.”

In this context, the genetic blueprint of humankind may serve as a roadmap for corporate growth as well as for the development of advanced imaging tools.