Focusing on macular degeneration.
There are two forms of AMD--wet and dry. About 80 to 90 percent of AMD cases represent the dry form, while the remaining 10 to 20 percent develop the more serious wet form.
In wet AMD, blood vessels in a layer underlying the macula proliferate uncontrollably--a process called neovascularization--then begin to leak into the retina. Although no treatment for the dry form of the disease is yet available, laser, pharmaceutical, and gene therapies offer hope to patients coping with the more damaging wet form of the disease.
To learn more about promising areas of investigation, Neighborhood Heart Watch (NHW) spoke with Dr. Mark H. Criswell, director of the Retina Service Research Laboratories at Indiana University School of Medicine and a recipient of pilot project funding for this important investigative research from the Indiana Center for Vascular Biology and Medicine.
NHW: Has photodynamic therapy proven effective for all patients with AMD?
MC: Photodynamic therapy utilizing Visudyne[R] has been out now for three years, and it represents a major advance. Essentially, the therapy does help close down new vessel proliferation, seals them off, and yet does not damage surrounding tissues. But we have learned that only about 20 to 30 percent of patients with the wet form of AMD are eligible for the treatment. Another limitation of the photodynamic therapy is that patients typically need to undergo the treatment every two to three months to continue to fight this ongoing process. The blood vessels will grow back because the therapy fails to address the underlying process of the disease.
NHW: Could you tell us about emerging therapies?
MC: Researchers are looking at a wide variety of therapies and agents--including steroids, nonsteroidal anti-inflammatories (NSAIDs), and other therapies working at the cellular level--to stop the neovascularization process.
We are also investigating anti-angiogenic agents that could inhibit or prevent new blood vessel growth. If we can come up with a good anti-angiogenic agent coupled with photodynamic therapy, we would have a way to treat damage that has already occurred and possibly block new vessel development in the future.
We have been working with colleagues at the National Eye Institute on new methods of drug delivery. Instead of delivering agents with an intravitreal injection (directly into the eye), we are testing micro-implants that allow slow release of a given drug. In this way, you get measured release over time with less toxic effects.
Others are investigating small pump delivery devices to disseminate the drug into the eye, but not throughout the body.
Another drug in clinical trials is called the VEGF (vascular endothelial growth factor) trap. On the cellular level in AMD, molecules called growth factors are released from damaged cells. Growth factors, like VEGF, are the molecular signals for neovascularization to begin in AMD patients. The drug traps these VEGF molecules, thereby blocking their effect on surrounding cells to initiate the abnormal neovascularization process.
Other groups are investigating the use of specialized radiation treatments to selectively destroy new blood vessel development. I am investigating a number of novel approaches across the spectrum. For example, I am collaborating with Dr. Keith March's group on the effects of growth factors, in particular hepatocyte growth factor (HGF). Whereas growth factors such as VEGF and HGF may both be important in initiating the angiogenic process for new vascular cell development, HGF may further be involved in the process of forming blood vessels from these new cells and in determining where these new blood vessels will grow.
Welcome Aboard, Keith March, M.D., Ph.D.
A brilliant and prodigious researcher and inventor, Dr. Keith March joins our newsletter staff as editor of the Indiana Center for Vascular Biology and Medicine news page. Dr. March is director of the Indiana Center for Vascular Biology and Medicine (ICVBM) at the IU School of Medicine. Dr. March and his team of 30 investigators at the ICVBM will report on their research in the areas of cutting-edge medical therapies, using advances in genomics and molecular biology, to improve the care of patients with vascular problems.
In the next issue, we will highlight the research of Dr. Edward F. Srour, researcher at the IU Cancer Center and professor of medicine and pediatrics at Indiana University School of Medicine.
For more information about the work of the Center and current research efforts, contact Dr. Keith March at 317-278-0130 or e-mail: firstname.lastname@example.org.