HJLR Mar/Apr 2019

Healthcare Journal of LITTLE ROCK I  MAR / APR 2019 51 If you saw this story, you might have quickly turned the page of your newspaper or internet browser and mentally filed this material as fanciful science bordering on fic- tion—definitely not a concern for contempo- rary healthcare, especially not inArkansas in 2019. But you would be wrong. Gene editing is heading our way soon and could be an interesting topic for theArkansas Medicaid program. CRISPR technology has been a hot topic in the biosciences for most of this decade and in biotech investing in the last few years. CRISPR stands for Clustered Regularly Inter- spaced Short Palindromic Repeats. It refers to the discovery that bacterial cells have genetic mechanisms to protect themselves from viral invasion of their intrinsic DNA. This defense mechanism relies on an endonuclease Cas9 that targets naturally repetitive genetic se- quences and excises foreign DNA material introduced by viruses. Clever laboratory ex- periments were able to use Cas9 as a tool to edit any sequence of cellular DNA. In fact, gene editing has become highly specific and reliant on inexpensive laboratory materials. In a sense, researchers found a biologic mechanism to “word process” amino acid sequences, and they can now delete, correct, or insert genetic material in a cell. This tech- nology opens the door to a whole newworld of genetic engineering in plants, bacteria, and possibly humans. At this stage, no one is quite sure whether the editing is truly specific. Are other unknown genetic sequences changed, and to what effect? Hence, the editing of em- bryonic DNA in a future human could affect numerous unknown developmental signals across numerous cell lines. Such intervention has frightening potential to induce unknown genetic defects in utero. On the other hand, targeted application of CRISPR principles in a specific cell line has exciting potential. Imagine editing red blood cell precursors to induce a patient’s own bone marrow to produce normal hemoglobin and cure sickle cell anemia. This concept is un- der active development and might be widely available in the next five years. Spinal Muscular Atrophy (SMA) is a ter- rible genetic disorder that, until recently, had modest supportive treatments for the condition that afflicts one in every 10,000 births, the most common inherited pediatric lethal disease. In the last two years, a new drug called nusinersen was approved by the FDA. Nusinersen can slow the progression of the disorder in about 50 percent of patients with type II and type III SMA by increasing production of an important motor neuron protein. Injections are given into the spinal canal four times in the first year and every six months thereafter. Cost of the medica- tion approaches $750,000 in the first year. Early results are promising, but more data are needed to fully understand the stabil- ity of the clinical improvements. Because of this progress, the American College of OB- GYN (ACOG) and several state legislatures have recommended that the screening test for SMA be included in the mandated panel of bloodwork for all newborns in our com- munities. Such early screening could identify those children who could benefit from early treatment and forestall clinical deterioration. While nusinersen is an interesting im- provement for SMA, researchers have ac- tively used CRISPR techniques to induce cells to produce normal proteins and eliminate the deficiency that leads to the terrible disabilities of spinal muscular dystrophy. AVXS-101, Zol- gensma, may come on the market in 2019. Its developer is already working withMassachu- setts Medicaid and other payers to accom- modate a $2-5 million price tag per patient. While successful interventions save lives and the costs of managing severe disabilities, the proposed price for genetic treatments will present an interesting economic challenge. One framework suggests an installment plan of payment over several years. Thus, the brave newworld of genetic edit- ing has arrived. It will affect many aspects of our lives from farming to health care. There is potential for abuse and for incredible new technologies. Research CRISPR on the inter- net or readACrack in Creation by bio scien- tist Jennifer Doudna. It is likely the start of a new tech revolution. n Sources Barclay, E., Belluz, J., Irfan, U., Plumer, B. (2018, December 27). A simple guide to CRIS- PR, one of the biggest science stories of the decade. Vox. Retrieved from  https://www.vox . com/2018/7/23/17594864/crispr-cas9-gene-ed- iting Doudna, J., & Sternberg, S. (2018). A crack in creation: Gene editing and the unthinkable power to control evolution. New York, NY: Houghton Mif- flin Harcourt. Specter, M. (2017, January 2). Rewriting the code of life. The New Yorker. Retrieved from https:// www.newyorker.com/magazine/2017/01/02/re- writing-the-code-of-life “CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It refers to the discovery that bacterial cells have genetic mechanisms to protect themselves from viral invasion of their intrinsic DNA.” WilliamGolden, MD Arkansas Medicaid Medical Director