Gene therapy may cure 2 blood diseases
Published: December 27, 2005
New York scientists have developed a stem cell-based gene therapy they say may cure two pervasive blood disorders, and the first round of human trials is expected to begin within six months.
Gene therapy is the technique in which a healthy new gene is incorporated into patients’ cells to correct a debilitating defect. The technique had raised ethical questions several years ago, but doctors have resumed studies. [Understanding Gene Therapy]
Sickle cell disease and thalassemia are related genetic disorders typified by encumbered red blood cells that are incapable of effectively transporting oxygen. The diseases affect tens of thousands of people worldwide, and can prove fatal. Unlike some inherited diseases that involve multiple genes, these disorders are single-gene defects, making them more amenable to this form of correction.
Scientists at Memorial Sloan-Kettering Cancer Center in Manhattan report in an online edition of Nature Biotechnology that they have developed a form of gene therapy that targets stem cells and restores effective oxygen delivery. The report focuses on sickle cell disease, but the team already has completed preliminary work on thalassemia and is expected to begin clinical trials by summer. [Hope and Destiny: A Patient's and Parent's Guide to Sickle Cell Disease and Sickle Cell Trait]
“The goal here is ambitious,” said Dr. Michel Sadelain, the study’s lead investigator, “because the purpose of this [research] is to achieve cures for both diseases.”
The research also will boldly utilize a killed lentivirus - HIV-1 - because of its keen ability to integrate into the chromosomes of cells. When thriving, HIV-1 can lead to AIDS. In this instance, however, the killed viruses will serve as vehicles, known technically as vectors, that will ferry healthy “globin” genes into stem cells.
Globin is the oxygen-carrying compound in red blood cells that is defective in both thalassemia and sickle cell disease. In the case of sickle cell, Sadelain said an additional technology, RNA-interference, will be part of the procedure. An RNA molecule will be used to correct the garbled instruction from patients’ DNA that transforms cells into crescents, a configuration that causes red blood cells to jam in capillaries, triggering excruciating pain.
The virtually painless technique is designed to be performed on an outpatient basis.
Stem cells produced in the bone marrow are collected from patients after they have been given a medication to boost their production. “Five or six days later, you [retrieve] stem cells that have collected in the blood, so you only need to draw blood. It’s that simple,” Sadelain said.
The cells then are cultured under sterile laboratory conditions and healthy genes are transferred into the cells’ chromosomes via the viral vectors. Before the cells are reinfused, patients are given a medication to tamp down their immune system and boost the likelihood that the newly altered stem cells will produce a healthy blood supply.
“I am extremely excited to be a part of this,” said Dr. Farid Boulad, medical director of the pediatric day hospital at Memorial Sloan-Kettering Cancer Center. As a clinician, Boulad will be involved in treating patients.
He said bone marrow transplants are used to treat thalassemia and sickle cell disease. But finding matched donors, he added, can be difficult. And even when a matched donor is found, patients still face the possibility that their immune system will reject the transplant. Gene therapy offers a way to infuse patients with their own cells.
“This treatment absolutely is a huge advance, especially for sickle cell patients” because it treats both debilitating aspects of the disease, said Dr. Selda Semakoglu, a member of Sadelain’s laboratory.
Gene therapy has only recently emerged from a cloud that enveloped it six years ago. Jesse Gelsinger, 18, died during a University of Pennsylvania gene therapy trial designed to treat his rare liver disorder. The youth’s death raised questions about the procedure, forced a halt to all gene therapy studies and sparked ethical debates.
With the government’s suspension now lifted, doctors have resumed clinical trials. A clinical study that involves the use of a lentiviral vector began earlier this year at the University of Pennsylvania.
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