Dr. Loh: Gene editing comes to the bedside
An earthquake in clinical care just occurred that may have slipped below the consciousness radar of most people. But I assure you that the implications and ramifications of this development will impact huge swaths of humanity when more applications and the inevitable reduction in costs become widespread.
Most diseases have a genetic component to them, whether it be causal or in the response to an illness. But some diseases are predominantly genetic in their origin, and sometimes the abnormality may be a single point mutation in the genetic code that is DNA.
Ever since the DNA that codes for what we are structurally was elucidated in the early 1950s by James Watson, Francis Crick, and the egregiously under recognized British chemist, Rosalind Franklin, we have come to realize that genetics plays a central role in our health and diseases. The massive human genome project laid out our chemical blueprint, but not what the codes actually meant. Myriad teams around the world have examined diseases and their genetic makeup, and have defined the abnormalities in exquisite detail. But until recently, we had no way do anything about these elucidated anomalies.
CRISPR is much more easily pronounced than its full name, Clustered Regularly Interspersed Short Palindromic Repeats. It was originally found as a bacterial defense system against attacks from viruses. After much intensive work by many august scientists, the technology that is CRISPR allows humans to clip out the desired part of a miscoded (if dealing with a disease) fragment of DNA and insert a normal piece in its place. If this is done in a cell that can reproduce, it will then pass on the normal gene code to its progeny.
What is truly amazing is that the Nobel Prize for CRISPR was awarded in 2020 to Jennifer Doudna and Emmanuelle Charpentier. In November, it was announced that the first approved CRISPR therapy in humans was granted in the U.K. for two genetic diseases for which there was no ostensible cure, only palliative therapies. U.S. approval may come later this year or early next year.
These first two diseases are blood disorders, sickle cell anemia and beta-thalassemia, which have errors in the codes for hemoglobin, the oxygen carrying proteins in red blood cells. These first CRISPR therapies are not curative in the absolute sense, but produce modifications to the patient’s hemoglobin so that it is less abnormal and thus mitigates the severity of the disease. Patients will need to be followed for essentially the rest of their lives to judge the true benefit of these novel interventions and to make sure there are no so-called “off target” effects, that is, unintended consequences.
Cardiovascular disorders are not too far behind, since well-defined genetic mechanisms are known and several companies are working on CRISPR based therapies for genetic cardiomyopathies and lipid disorders. Alzheimer’s and many other disorders are also on the CRISPR therapeutic roadmap.
We are moving from treating the results of disease or targeting the pathways of damage of diseases to actually going after the fundamental genetic mechanism of how a disease does what it does. At the current time, the patient has to undergo an arduous course of care not unlike a stem cell transplant, and the costs are very high. But look at this process as a clinical proof of concept, that genetic manipulation of a human disease is finally at hand, and in our children’s lifetimes, this may become a relatively routine intervention.
Moreover, it may stop genetic diseases from being further transmitted, thus saving future generations from the cost and debilitation of recognized genetic disorders. But let us not forget that when faced with the currently extraordinarily high costs of genetic manipulation, the low cost of genetic counseling when genetic diseases are known to run in families, should also be utilized.
Technological advances are often double edged, with promise of good also tempered by possibility of nefarious applications. But taken as a whole, this remarkable milestone is an example of science truly in the service of humanity.
Irving Kent Loh, M.D., is a preventive cardiologist and the director of the Ventura Heart Institute in Thousand Oaks. Email him at drloh@venturaheart.com.
This article originally appeared on Ventura County Star: Dr. Loh: Gene editing comes to the bedside
