Can new gene-editing tools provide the roadmap to a cure for myeloma? Part One
September 28, 2017
Can new gene-editing tools provide the roadmap to a cure for myeloma? Part OneWRITTEN BY: Brian GM Durie MD
CRISPR technology was the 2015 science breakthrough of the year. The discovery and implementation of this technology has set off a revolution in genetic research and treatment. But what does it mean for cancer, and specifically, might CRISPR technology be used to help find a cure for myeloma?
I will explore these questions in a two-part series of posts. Today, I will focus on what we know about CRISPR so far. Next, I will examine ways in which CRISPR might impact MGUS, SMM, and myeloma when used as a tool in early diagnosis, prevention, treatment, and, ultimately, finding the roadmap to a cure.
First, a bit of explanation: CRISPR stands for “clustered regularly interspaced short palindromic repeats” – words that hint at how CRISPR works. You may be surprised to know that this is an ancient technology used by the bacteria in our bodies. Bacteria targets areas along the DNA (“repeats” in the genetic code) to capture, insert, then cut out and remove invading viruses. The cutting is done by an enzyme named Cas9, a large protein that encircles the DNA, cuts out the bad piece, and replaces it with normal or other DNA. An excellent video from the McGovern Institute for Brain Research at MIT gracefully explains the CRISPR process.
In 2015, two competing research teams—one based at Harvard University and the Broad Institute, the other at UC Berkeley and the Helmholtz Centre for Infection Research in Germany – reported successful gene editing with CRISPR.
An early thought was that bad genes linked to cancer could be removed, which has led to one of the first patient trials – in lung cancer – just starting in China.
To understand the broad potential of gene editing, it is helpful to look at five recent applications, as identified in MIT Technology Review:
1. Treating cancer with a topical gel or cream.
It may seem like science fiction, but this is how it works. The HPV (human papilloma virus) enters the cells of the cervix and can cause cancer. Gene editing can be used to edit out the virus and thus prevent cancer. In the TALEN (Trans Activator-like Effector Nuclease) clinical trial women with HPV infections apply a gene-editing enzyme in a gel to the cervix twice a week for four weeks. TALEN, an earlier iteration of gene editing, is not as precise as CRISPR. Still, indications are this will remove the virus. The trial is beginning at Sun Yat-sen University in Guangzhou, China.
Again, sounds a bit like science fiction. Drink a probiotic-type yogurt with bacteria carrying the enzyme to destroy antibiotic-resistant bacteria. Bad bacteria are destroyed; good bacteria remain intact. Researchers are now looking at the body’s resistance to therapies other than antibiotics, including myeloma drugs.
3. By injection.
When you are deaf, the tiny hairs in the middle ear don't work well. By injecting CRISPR as a fatty gel material (liposomes) into the middle ear, the hair cells can be treated. The TMC1 gene is cut out. Hearing improves, but by how much remains to be seen. Results, again in China, are preliminary at this time.
4. By skin graft.
This is a simple idea – treat diabetes by adding the insulin gene to a skin graft. It seems like it will work well. There are myriad opportunities for this skin-grafting approach.
5. Manipulating cells outside the body and re-injecting.
This is a method we have seen with the CAR T-cell therapies. The team at the University of Pennsylvania is now using CRISPR technology to engineer and re-infuse molecularly tailored T-cells to attack myeloma. Again, these are early days – in part because of possible toxicities – but the method has great potential.
While CRISPR offers the world enormous opportunities, ethical issues will no doubt loom large. Most people would not have a problem editing out so-called bad genes. A slippery slope arises when we consider the possibility of enhancing or changing good genes, like muscle strength, eye or hair color, or any number of other features. True medically necessary gene editing will have to be distinguished from the cosmetic or more fanciful.
Just how will all these CRISPR applications be applied in myeloma? The options are so diverse that they require—and deserve—a follow-up blog post. For now, I’ll say that the roadmap to finding a cure has a lot more details. The applications are only limited by our imagination.
Part Two: Dr. Durie looks at the role CRISPR could play in the prevention, diagnosis, and treatment of multiple myeloma.
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