Gene therapy treats genetic disease at the molecular level by correcting, editing or otherwise manipulating defective genes. Gene therapy depends on a corrected gene being delivered to target cells and continue to work properly, long term, without adverse effects. As human beings, our time in the womb is critical to the rest of our existence. As such, healing disease at this time is the ideal preventive therapy. Gene and stem cell therapy used after adulthood are performed on parts that are fully formed. If these therapies are used before birth, the problem may be solved before it ever manifests.
William French Anderson, is considered the “Father of Gene Therapy” and the first scientist to propose gene therapy in utero to the National Institutes of Health in 1998. In 1990, a 4-year old patient became the first recipient of gene therapy. She had adenosine deaminase deficiency (ADA), an inherited metabolic disorder that causes immunodeficiency, leaving the body incapable of fighting disease. White blood cells were taken from her and grown in a lab. Scientists then inserted the missing gene into the cells, and infused the genetically modified white blood cells back in to the patient’s bloodstream. After the procedure, lab tests showed the patient had a 40% stronger immune system. While the procedure was not a cure, and needs to repeated every few months, the patient is currently still in good health.
Since this first breakthrough procedure, advances in molecular testing have made it possible to diagnose many genetic disorders early in gestation with minimal risk to the fetus. Prenatal screening for the majority of human genetic diseases allows for treatment and correction prior to birth. In fact, researchers from Carnegie Mellon University and Yale University used gene editing for the first time in history to successfully cure a genetic condition in a mouse. “Early in embryonic development, there are a lot of stem cells dividing at a rapid pace. If we can go in and correct a genetic mutation early on, we could dramatically reduce the impact the mutation has on fetal development or even cure the condition,” said Danith Ly, professor of chemistry in Carnegie Mellon’s Mellon College of Science.
In Germany, a prenatal protein injection in an expectant mother’s amniotic fluid produced successful results in treating X-chromosomal hypohidrotic ectodermal dysplasia (XLHED). Individuals who suffer from XLHED lack the EDA1 protein normally found in the body that is responsible for the development of hair, teeth and skin appendages such as sweat glands while the fetus develops in the womb. Three children were treated at University Hospital Erlangen by Prof. Dr. Schneider and PD Dr. Faschingbauer by using ultrasound to oversee the procedure, PD Dr. Faschingbauer carefully injected 15 ml of the medicine into the amniotic fluid. Thanks to the drug, their sweat glands developed normally, and no ectodermal dysplasia-related illnesses have been observed thus far in the infants, who are between one and two years old (N. Engl. J. Med. 2018, DOI: 10.1056/nejmoa1714322).
Further, in December 2017, the U.S. Food & Drug Administration approved its first gene therapy, for a rare eye disorder that can cause blindness.
Despite these impressive results, there are questions raised that underscore the limitations of in utero gene therapy. The biggest question among many researchers is whether gene therapy is permanent. This question, among others, will require further research and observation, but there is no question that the outlook is promising.
- Adele S. Ricciardi, Raman Bahal, James S. Farrelly, Elias Quijano, Anthony H. Bianchi, Valerie L. Luks, Rachael Putman, Francesc López-Giráldez, Süleyman Coşkun, Eric Song, Yanfeng Liu, Wei-Che Hsieh, Danith H. Ly, David H. Stitelman, Peter M. Glazer, W. Mark Saltzman. In utero nanoparticle delivery for site-specific genome editing. Nature Communications, 2018; 9 (1) DOI: 10.1038/s41467-018-04894-2
About the author
PhD, MS, MPH, is the President and CEO of Phronetik, a biotechnology company headquartered in North Texas.