Fabry disease is a genetic condition in which a defective GLA gene causes a lack of the alpha-galactosidase A enzyme. Damage to organs and systems such as the heart, kidneys, nerves, brain, intestinal tract, and skin are common in this condition due to an abnormal accumulation of a substance called globotriaosylceramide (Gb3 or GL-3), which normally is broken down by the alpha-galactosidase A enzyme.
Gene-editing therapy for Fabry disease is currently in the pre-clinical stage; no clinical trials have been done on humans yet.
What is gene editing?
Gene editing is a type of gene therapy that is much more specific and capable of correcting very small segments of DNA.
Gene editing uses so-called “molecular scissors’ that are able to precisely cut the DNA at desired locations to remove or add sequences.
There are different gene-editing techniques, including zinc-finger nucleases and TALENs, but the latest and most sophisticated method is the CRISPR/Cas 9 system. These “molecular scissors” are put into carriers or vectors, such as inactivated viruses, in order to transport them inside the cells that need to have their DNA edited.
Gene editing is being investigated for the treatment of a broad range of medical conditions, including infectious disease, primary immunodeficiencies, blood disorders, and muscular dystrophy.
Gene editing therapy for Fabry disease
California-based Sangamo Therapeutics (previously known as Sangamo BioSciences) is experimenting with a zinc-finger gene-editing molecule inserted into an adeno-associated virus (AAV) for the treatment of Fabry disease.
Researchers designed the zinc-finger gene editor to specifically insert the normally functioning gene into the albumin gene sequence. (Albumin is a protein made exclusively by the liver.) They hypothesize that integrating the gene there would stabilize it enough for it to be able to produce the normal alpha-galactosidase A enzyme.
A single infusion of this compound into mice that were genetically altered to have Fabry disease was able to increase the levels of the alpha-galactosidase A enzyme by 10 to 100 times. Moreover, the newly produced enzyme was taken up readily by the heart and kidneys, clearing abnormal G3b build-up. Sangamo plans to proceed to human clinical trials with this compound.
A separate research group has used the CRISPR/Cas9 gene-editing technology to create a human cell model for Fabry disease that can be used to test and improve the effectiveness of medications for the condition.
The safety and ethical issues that arise with the newfound ability to directly alter our DNA with gene-editing technology are hotly debated. While experiments indicate that gene editing could have the potential to greatly help those with genetic conditions, scientists are concerned with its safety because there is a risk of mistakenly editing the wrong segment of DNA.
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