Promising Prospects of Gene Therapy
Overview of Genetic Disorders
Genetic disorders are hereditary diseases resulting from defects in an individual’s DNA. As these conditions remain incurable, patients often rely on lifelong medications that primarily address symptoms. However, recent advancements in molecular biology and genetics have introduced gene therapy as a potential groundbreaking approach to treat these genetic illnesses.
Mechanism of Gene Therapy
Gene therapy involves a therapeutic strategy aimed at correcting, facilitating, or reprogramming defective DNA within a patient. The technique gained prominence following its first successful application in humans by scientist William French Anderson in 1990, who treated a four-year-old girl suffering from severe immune deficiency.
Typically, gene therapy begins with the incorporation of a healthy gene into a virus. This engineered virus is then administered to the patient, targeting the affected area. The virus infects the diseased cells, delivering the healthy gene, which the cells use to restore normal functions. Although the concept of utilizing viruses for treatment may seem counterintuitive, the viruses employed are generally harmless and can be modified to present less health risk compared to their natural counterparts. Nonetheless, findings from a recent animal study published in Science suggest that gene therapy may harbor previously unrecognized risks.
Identifying Risks Associated with Gene Therapy
Study Findings
Researchers investigating adeno-associated virus 9 (AAV9), a typically harmless virus, discovered that high doses administered to monkeys and pigs resulted in significant liver and neuron damage. These alarming results prompted Dr. James Wilson, the lead scientist, to caution clinical researchers about the potential side effects when applying gene therapy in human patients.
Expert Opinions and Reactions
Dr. Terence Flotte, Dean of the School of Medicine at the University of Massachusetts, urged the medical community to avoid overreacting to these findings. Previous clinical trials have demonstrated that AAV9 effectively treated 15 infants diagnosed with severe spinal muscular atrophy, a rare and deadly neurodegenerative disorder. Most of these infants can now stand, and two have even begun to walk.
However, Dr. Wilson’s research indicated that high doses of the AAV9 virus, which carried the same healthy genes, resulted in liver toxicity in three rhesus monkeys, ultimately leading to the euthanasia of one. Similar adverse effects were observed in three piglets, which also suffered nerve damage and were subsequently euthanized.
Exploring Contributing Factors
Dr. Flotte expressed concerns regarding the unexpected results of the study, highlighting several critical factors. Firstly, he noted that the strain of AAV9 utilized in this research differed from that used in previous clinical trials, potentially leading to unpredictable outcomes at elevated doses. Additionally, the genes employed in the experiments were of human origin, which may not be compatible with animal models, resulting in severe reactions.
While these findings suggest a possible risk for patients considering gene therapy, further research is essential to verify the validity of these risks. Dr. Jude Samulski, a gene therapy researcher at the University of North Carolina School of Medicine, emphasized the need for reproducibility of the results to assess any potential concerns accurately. He anticipates that additional laboratories will seek samples of Dr. Wilson’s virus for further investigation and validation.
References
(1) Kaiser, Jocelyn. New animal study raises concerns about high-dose gene therapy. http://www.sciencemag.org/news/2018/01/new-animal-study-raises-concerns-about-high-dose-gene-therapy
(2) John Wiley and Sons Ltd. Phases of Gene Therapy Clinical Trials. http://www.abedia.com/wiley/phases.php
(3) Angier, Natalie. Girl, 4, Becomes First Human To Receive Engineered Genes. http://www.nytimes.com/1990/09/15/us/girl-4-becomes-first-human-to-receive-engineered-genes.html