Column 5 min read

Genome Culture: Genetics Fulfills Some Old Promises in 2017

A look at the top genetic therapies that showed successes this year.

By Laura Hercher featured image ANDRZEJ WOJCICKI /Getty Images

For decades, genetics has been the science that cried wolf.

Stem cell therapies were going to regenerate our aging body parts in the 1980s. Gene therapy was going to free us of genetic disease in the 1990s. The Human Genome Project was going to fix EVERYTHING as the clock struck on the new century. Quantum leaps were promised, incremental steps delivered. Enthusiasts grew jaded, and skeptics grew more skeptical.

Wolf. Wolf. Wolf!

Seriously, I’m not kidding. The wolf we’ve been waiting for is finally here.

Mark it on your calendar: 2017 is the year when genetics began to deliver on its promises.  Here are some of the 2017 success stories that ushered in a new era of genetic medicine:

CAR T Therapy

The great promise of chimeric antigen receptor (CAR) T therapy is to harness the body’s own immune system, using cells called T cells to eliminate cancer with efficiency and precision, and reducing the toxicity of traditional chemotherapies that do not target cancer cells selectively. People have been excited about the potential of immunotherapy for years, and studies using genetically modified T cells have produced some miraculous successes, but the field has also seen setbacks, including early versions derailed by unexpected deaths among participants.

Finally, in August, the FDA approved the first CAR T therapy for clinical use, a drug called Kymriah that treats a pediatric form of leukemia. One month later, the FDA approved Yescarta to treat some forms of B-cell lymphoma. Reason to celebrate: the first of what is certain to be an important class of cancer therapies.

Gene Therapy

Spinal muscular atrophy (SMA) is an untreatable genetic condition that frequently results in the death of young children. At least, that is what it was until a year ago, when the FDA approved Spinraza, a Biogen drug that improves outcomes for SMA patients, though at a cost of $750,000 in just the first year.  But Biogen may not have long to enjoy its monopoly on hope for SMA families. Several companies have begun clinical trials for SMA gene therapies. And an article in the New England Journal of Medicine reported encouraging results from a small study of AveXis’s gene therapy for SMA in November.

The SMA success story is one of several that point to a sort of renaissance for gene therapy, which has seen every earlier positive result undercut by side effects, including malignancies and severe reactions to the virus used to deliver the drug.

This time, two trends have increased the odds of success. First, technological advances have made gene editing quicker, easier, and cheaper. Second, researchers appear to have found a better and less toxic delivery system.  That’s why the list of diseases currently targeted in gene therapy trials is now pretty long, and includes sickle cell, thalassemia, hemophilia, and a range of metabolic disorders. Capping the year’s list of gene therapy milestones, this week the FDA also announced the first approval of a gene therapy drug, which treats a rare retinal dystrophy that can cause blindness.

RNA Interference

The best candidates for gene therapy are diseases where a single missing protein is the key to a cure. If you can get a copy of the gene into the cell and turn it on, the problem is fixed. Other diseases are caused by an aberrant protein, a sort of loose cannon, causing damage or interfering with normal function. In these cases, it is not enough, and may not be necessary, to introduce a working copy of the gene. The key here is to silence the destructive variant.

One example of this type of pathology is Huntington’s disease, in which the cumulative damage to the brain results in cognitive decline, psychiatric disease, and the symphony of uncontrolled tics and jerks called chorea. Hope of a possible treatment for this dreadful disease came in December, with a report of a small, preliminary study using a technique called RNA interference. This type of therapy targets the RNA molecule shuttling instructions from the DNA to the cellular machinery where proteins are assembled. By blocking the RNA messenger, the therapy prevents the body from creating the abnormal protein that is responsible for the damage that causes the disease.

The technique has already shown success in treating another rare disease involving an aberrant transthyretin protein. And the early results for Huntington’s are also promising, as it appears to have decreased levels of the toxic protein in the brain without endangering patients.

Stem Cell Therapy

This is the single greatest story of 2017.

If you can bring yourself to do it, for just a minute, imagine this: a disease that makes your skin so fragile that it blisters and tears with the slightest contact. In 2015, a boy with a severe form of this disease, called epidemolysis bullosa, lay in a hospital in Germany. Nearly 60 percent of his body was a gaping, skinless wound. Instead of sending him to hospice care, doctors removed a tiny fraction of what skin the boy possessed and sent it to researchers in Italy. There, scientists succeeded in correcting the genetic defect in his skin stem cells and used them to grow sheets of new skin for grafting. In 2017, the boy is healthy, in school, and blister-free.

Clinical applications of new genetic technology will open the door to more amazing stories like this in 2018 and beyond. Soon, the operative questions will not be about what we can do but about what we can afford. So congratulations 2017, and in the new year, it is time to talk about costs.