A recent study by several HCM genetics researchers around the globe, led by Australia’s Dr. Jodie Ingles, found that 2/3 of genetic mutations previously reported to patients as HCM causative may actually NOT trigger HCM.
Scientists, in a follow up to three earlier, less successful, Chinese experiments, have for the first time used a recently developed gene editing process known as “CRISPR” to remove a genetic defect from a human embryo. The specific defect that the scientists targeted was a mutation in MYBPC3, a common genetic cause of hypertrophic cardiomyopathy (HCM).
What Happened in the Study?
The study authors consisted of a multi-national team of geneticists, cardiologists, fertility experts and embryologists. Led by Dr. Shoukhrat Mitalipov of Oregon Health Sciences University, in collaboration with researchers at the Salk Institute in La Jolla, CA, China and South Korea, the researchers were able to largely remove the HCM gene MYBPC3 from very early stage human embryos.
Their research involved using eggs from 12 healthy female donors, and sperm from a male HCM patient with the MYBPC3 gene. When gene-editing components were introduced to the egg along with the sperm, prior to fertilization of the egg, approximately 3/4 of the embryos repaired themselves using the DNA blueprint provided by the normal, non-mutated copy of the gene from the unaffected female. This was somewhat surprising to researchers, who had theorized that cells would replicate using a blueprint from the repaired paternal gene – not the healthy gene of the mother.
Ultimately, genes were corrected in 42 of 58 embryos, constituting 72.4% of the total, a higher proportion than expected, and far more than any correction shown in previous experiments.
Implications for the Future
This technique is still far from general usage and will require further study and refinement. And, currently it is not legal in the United States since the Food & Drug Administration currently prohibits medical gene editing which would impact future generations.
However, it would be possible for this technique to be used alongside current technology to assist families with genetic diseases like HCM. If used in conjunction with pre-implantation genetic testing and in-vitro fertilization (PGD), the technique could repair the large proportion of embryos (roughly 50%) which must be discarded due to genetic defectiveness.
While there are critics who say that this technology will lead to “designer babies” and that it creates troubling ethical issues for society, most HCM patients believe that it provides a ray of hope, so that hopefully one day, in the not-too-distant-future, our children and grandchildren will be free of the affliction that has permeated our lives, as well as the lives of our siblings, our parents, our aunts and uncles, our cousins, our grandparents, and our great-grandparents.
As this story was reported by all major news sources, links to many of the articles can be found below.
NOTE THAT APPROXIMATELY A MONTH AFTER THE PUBLICATION OF THIS ARTICLE, THE RESULTS HAVE BEEN CALLED INTO QUESTION BY OTHER SCIENTISTS.
See this article in MIT Technology Review, this article in Science Magazine, this article in Nature, and this article in The Scientist, all of which cite this article in BioRxiv which poses alternative theories for the results claimed by the original paper.
A recent study followed 14 patients carrying one of two known genes associated with HCM (MYBPC3 and MYH7) over a 10+ year period . At the time of gene identification, none of the patients shown clinical evidence of hypertrophy. Over the time span of the study, 3 patients, who were then adults, had developed signs of HCM. Hence, the study suggests that periodic screenings are necessary for gene positive individuals throughout adulthood.
According to Cardiomyopathy U.K., the researchers undertook this project due to the lack of information and guidelines available to patients who are gene positive but have no outward signs of the disease.