Weill CU research results in successful embryo biopsy for deadly eye cancer

Prior to a Jan. 28 press conference in New York City, Dr. David H. Abramson, center in white coat, director of the Ophthalmic Oncology Center at NewYork-Presbyterian/Weill Cornell, meets with Larry and Anne Zimmerman and their children. Luke, 7 months, in green sweater, and, Lizzie, 18 months, in black dress, are the world's first two babies to benefit from PGD screening for the genetic defect retinoblastoma. Abramson is holding their daughter Perry, 3. Dr. Antonio M. Gotto Jr., dean of Weill Cornell Medical College, is in the background, left. Richard Lobell

By Sean Kelliher

In a significant scientific achievement, physicians and scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have successfully used preimplantation genetic diagnosis (PGD) for retinoblastoma, resulting in the world's first babies born free of the deadly inherited eye cancer.

Details of the research appear in the January 2004 issue of the American Journal of Ophthalmology.

Preimplantation genetic diagnosis, or embryo biopsy, is a diagnostic technique used with in vitro fertilization to determine the genetic status of embryos before implantation. The technique allows parents to know with reasonable certainty that their child will be normal before conception. Moreover, PGD can virtually eliminate the risk of passing on a genetic trait from parent to offspring and forever end a family's history of dealing with a deadly disease.

Retinoblastoma, the most common primary cancer of childhood, is transmitted between a parent and offspring. If a parent has bilateral retinoblastoma (in both eyes), there is a 50 percent chance of a child being affected with each pregnancy, with often devastating results. Children with the gene typically develop retinal tumors and are more likely to succumb to other forms of cancer as well. Among these are osteosarcomas of the skull or extremities, soft-tissue sarcomas and melanomas (skin cancer).

Retinoblastoma occurs in 1 in 15,000 births; one child is born with the disease every day in the United States. It is fatal if untreated.

Rosenwaks

Xu

The interdisciplinary team from NewYork-Presbyterian/Weill Cornell was led by Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility; Dr. David H. Abramson, director of the Ophthalmic Oncology Center; and Dr. Kangpu Xu, a noted embryologist and expert in PGD technology. Other key contributors included Dr. Ina Cholst, Dr. Lucinda Veeck and Katherine Beaverson.

Dr. Antonio M. Gotto Jr., dean of Weill Cornell Medical College, said: "Our breakthrough with retinoblastoma is a wonderful achievement. Our team has used this relatively new technology to combat a number of genetic defects and chromosomal abnormalities, leading to a relief of pain and suffering."

Dr. Herbert Pardes, president and CEO of NewYork-Presbyterian Hospital, observed: "Such an achievement can only be realized in an academic medical center, such as ours, where specialized, multidisciplinary teams of physicians and scientists can create a unique synergy between bench and bedside, between research and patient care."

A microscopic image of a single cell being taken from a three-day-old embryo. The single cell is then screened for retinoblastoma using DNA analysis. NewYork-Presbyterian/Weill Cornell

According to the research report, the physician-scientists used leuprolide acetate and gonadotropins to hyperstimulate the mother's ovaries, and the resulting eggs were harvested and fertilized using an in vitro fertilization technique that Rosenwaks helped popularize a few years earlier. After several days, a single cell, or blastomere, was biopsied from each resultant embryo and its DNA examined. Testing was done using polymerase chain reaction and restriction enzyme analysis. An embryos that was determined not to carry the retinoblastoma gene defect was implanted within the mother's uterus. The mother had two successful pregnancies and births through PGD, resulting in a baby girl and, later, a baby boy.

In contrast, the couple's first child, conceived without PGD screening, was born with the genetic defect and developed retinoblastoma, or tumors of the retina, at a young age. She currently is undergoing treatment for a brain tumor.

The father, who carries the genetic defect, was born with retinoblastoma and treated as a child. He has reduced vision in one eye as the result of the disease.