Dr. Aaron Roller Sheds Light on New Gene Editing Therapy
New research recently published in the Journal of Experimental Medicine suggests that an innovative form of CRISPR gene editing may help restore vision in those affected by retinitis pigmentosa (RP), a leading cause of blindness. This gene editing breakthrough is showing promise at proving even more effective on laboratory mice than the standard gene therapy currently used to treat this condition.
In this blog, Dr. Roller is sharing his insights on traditional gene therapy versus the new gene editing treatment to treat RP.
What is retinitis pigmentosa?
Retinitis pigmentosa is a broad term that encompasses many different specific disease entities, each due to genetic mutations in specific genes involved in the metabolism of the retina and adjacent tissues.
Why is this new research important?
Advances such as this are critical to the development of more effective treatments for inherited retinal diseases in humans, and moreover to the possibility of treating a wider range of inherited disease than previously considered possible with current techniques.
How does gene intervention help to correct defective genes and restore vision?
Genetic treatment approaches aim to correct the defective genes by either supplying entire normal genes to compensate for the defective ones (gene therapy), or by replacing specific genetic mutations with normal genetic information (gene editing).
Of these approaches, gene therapy is currently at the forefront of medical treatment. All of the numerous current clinical trials for retinitis pigmentosa utilize gene therapy, most commonly by means of a viral delivery system to provide normal copies of genes to the retina in patients with genetic mutations. These trials are all very promising.
The only FDA-approved treatment of retinal disease utilizes viral gene therapy to restore useful vision in patients with blindness due to Leber congenital amaurosis, a condition similar to retinitis pigmentosa.
What are the limitations of gene therapy?
Despite the success of gene therapy, significant limitations exist.
Gene therapy approaches most commonly employed in present clinical trials are only theoretically able to treat a certain subset of genetic disease. Many of the most common and devastating forms of retinitis pigmentosa and other retinal dystrophies remain out of the reach of standard gene therapy techniques.
How might gene editing prove more successful than traditional gene therapy at restoring vision?
Gene editing has the potential to be a new paradigm in treatment of retinitis pigmentosa, as it offers the potential to circumvent some of the inherent limitations of gene therapy and greatly expand the number of specific genetic mutations that can be treated.
For example, many of the genes implicated in RP are simply too large to fit into most currently utilized gene-delivery systems. Since gene editing modifies the existing genetic information, a size limit does not apply, greatly expanding the range of treatment options for different forms of RP.
What is the main difference between gene therapy and gene editing?
One critical difference is that while gene therapy is most effective in cases of recessively-inherited genetic diseases (which generally only affect a single generation in a family), gene editing has greater potential to treat diseases of all inheritance patterns, including diseases in which many family members of different generations are affected.
What do further advancements in gene therapy and gene editing technologies look like?
While gene editing is still a few steps behind gene therapy with respect to human treatment trials, the technology is evolving at an explosive pace, and the potential applications are incredibly broad. Between gene therapy, gene editing, and other emerging concepts for the treatment of RP and related conditions, it seems likely that effective treatments will continue to become available at a rapidly increasing pace over the coming years. Whereas until now, a diagnosis of RP was often a guarantee of gradual progression towards severe vision loss, these new treatments hold promise for a lifetime of functional vision for many patients.
Which patients are most likely to benefit from this new form of gene editing therapy?
For patients who have already suffered severe vision loss from many forms of RP, genetic treatment will not likely be able to restore vision that has already been lost, but only prevent further progression of vision loss. Therefore, with some exceptions, patients who stand to benefit most from genetic treatment are those in early stages of disease progression.