• Biotherapeutics

    Delivering innovative stem cell therapy to slow vision loss

The regenerative eye scientist, Alan Marmorstein, Ph.D., is drawn to research by the need to find new cures for diseases. As an aspiring researcher, he never envisioned his investigative journey would take him down the path of testing ways to prevent or restore loss of eyesight. However, a post-doctoral lab assignment, a National Eye Institutes grant and inspiration from retina surgeons presented him the opportunity to research disorders of the eye. It launched him on a transformative career trajectory.

Alan Marmorstein, Ph.D.

“Initially, I was disappointed, because I was interested in pursuing a different line,
 says Dr. Marmorstein. “After I started working in the lab, I fell in love with the eye as a system. The eye is a unique organ in the body that you can literally look into. You can monitor what you are doing and see the effect of your research much easier than in a lot of other places in the body. It’s very easy to figure out if something can see.”

At Mayo Clinic, Dr. Marmorstein’s research to prevent blindness includes delivery of stem cell replacement therapy to slow or stop progression of diseases that rob people of their central field of vision. Mayo Clinic Center for Regenerative Medicine supports Dr. Mamorstein’s research as part of its mission to empower discovery, advance the practice and develop new cures that address unmet patient needs.

Research focus

Dr. Marmorstein’s research focuses on age-related macular degeneration and an inherited form called Best disease, which typically afflicts people under the age of 65. Macular degeneration is a loss of central vision and a leading cause of blindness in older adults. It affects more than 10 million Americans, according to the American Macular Degeneration Foundation. While there are eye injections to ease symptoms of some forms of macular degeneration, researchers are trying to solve the puzzle of how to stop the progression and ultimately cure the disease.

“The goal of our research is to keep as many people as we can from losing their central vision. Very likely any future treatments will involve a surgical intervention. We are seeking a therapy that’s off the shelf, meaning that patients can be treated readily. Our hope is that once someone is diagnosed we could immediately offer a date for surgery,” says Dr. Marmorstein.

In dry macular degeneration, the center of the retina deteriorates. With wet macular degeneration, leaky blood vessels under the retina cause blurred vision. Little is known about the cause of age-related macular degeneration. Best disease is linked to a genetic mutation affecting retinal pigment epithelial (RPE) cells, which are the layer of cells that support the health and function of light sensing cells in the retina. RPE cells are essential to maintaining vision.

Stem cell therapy

Working with the Center for Regenerative Medicine Biotrust, Dr. Marmorstein’s team is engineering replacement RPE cells derived from induced pluripotent stem cells (IPSC). The process is like turning the clock back in time to when the stem cells were first forming in the mother’s womb. At that time, cells were dividing and differentiating and could become any type of cell or tissue within the body. The human IPSCs are manufactured from tissues in the Biotrust and are reprogrammed to become retinal pigment epithelial cells that could replace the faulty cells linked to vision loss.

“The Biotrust provides us with cells from human skin samples. The expert staff at the Biotrust trained my team how to grow induced pluripotent stem cells from human samples. In addition, they provided us support in terms of finance, personnel and knowledge to do this research,” says Dr. Marmorstien.

In a further demonstration of ingenuity, Dr. Marmorstein’s team has developed a biodegradable scaffold for the delicate process of delivering the cells to the precise location within the retina where they are needed to potentially preserve or restore vision. While a plastic scaffold that would permanently remain in the eye has been used elsewhere, Mayo’s scaffold places the cell within the eye and disintegrates within two months.

“This is a unique instrument for delivering the RPE cells. The scaffold is manufactured from human fibrin, which is a protein that is naturally involved in blood clotting and wound healing,” says Dr. Marmorstein.

Dr. Marmorstein’s research team includes Jarel Gandhi, Ph.D., who designed the scaffold and Raymond Iezzi, M.D., an ophthalmologist who helped develop the surgical procedure.

A graduate of State University of New York at Albany, Dr. Marmorstein earned his Ph.D. at the State University of New York Health Science Center at Brooklyn and completed a post-doctoral fellowship at Cornell University. He began his research career at the drug company, Merck. After holding research positions at Cleveland Clinic and the University of Arizona, Dr. Marmorstein joined Mayo Clinic in 2013.

“I came to Mayo because of its unique blend of science, research, education and practice. The sharing of expertise is unmatched. I’ve had members of the retina surgical staff attending my lab meetings, and their input has been invaluable. My team draws on all available resources, such as the Biotrust, bioinformatics, biostatistics, engineering and assistance with regulatory issues to advance research,” says Dr. Marmorstein.

The key to advancing research into human clinical trials is to gain Food and Drug Administration approval for Investigational New Drug use of the RPE cells and biodegradeable scaffold in humans. Dr. Marmorstein hopes to clear that hurdle and test his research in phase 1 safety trials within 18 to 24 months.


Related Articles