Gene therapies bring genomic research to patients in life-changing ways

In November 2017, scientists took a leap forward and used gene editing to change the DNA inside a person to help fight a disease. Brian Madeux, 44, underwent a first-of-its-kind treatment targeting a deficient gene in his liver. Madeux has a genetic condition called Hunter syndrome. His DNA doesn’t produce an enzyme that breaks down polysaccharides, a key source of energy in the body. If those polysaccharides don’t get broken down, they build up in cells and wreak havoc on the body.

The treatment, administered in California, used zinc finger nucleases (ZFNs) to target the area of the genome in question. The ZFNs cut the DNA and slip in a new gene, which in turn, orders the cell to make the enzyme-producing protein the patient lacked. Only one percent of the liver cells need to be corrected for the treatment to be successful.

ZFN is a predecessor to the much-heralded gene editing tool called CRISPR. Both tools contribute to the increasingly diverse range of progress we’ve seen recently in gene therapies.

Gene therapies work by overriding or altering the genetics of the human body to fight disease.  Most often, the technique inserts a working copy of a gene into patient cells to rescue a nonfunctional version of the gene, like with Madeux. But they could also theoretically revolve around “knocking out” or turning off a mutated gene that isn’t working correctly so that it would stop harming the body. Scientists also hope to introduce all new genes into the body to help fight some diseases.

The goal is to treat disease at its source, rather than simply managing its symptoms. Gene therapy may be delivered directly to the patient’s affected tissues or to a subset of harvested cells that will subsequently be re-introduced into the body. Scientists have been pursuing these approaches for nearly four decades, but have achieved significant clinical success only within the last few years.

Success Stories

While these treatments have a long way to go before they become a go-to for clinicians, the successes of gene therapy do point to a promising future.

For example, the first gene therapy approved in the U.S. to correct a specific disease-linked gene has already improved the vision of dozens of patients affected by a rare form of childhood blindness. The vision problems come from mutations of the RPE65 gene, which scientists targeted by injecting billions of virus particles directly into the eye. The virus has been modified so it no longer causes an infection, but instead functions as a delivery vehicle, carrying a healthy copy of the gene directly into the retina.

The treatment, called Luxturna, improved light sensitivity and functional vision for 93% of the more than two dozen children and adults that went through clinical trials. The effects have lasted at least four years in the patients researchers have been able to follow that long. However, the treatment costs $425,000 per eye, raising questions about how quickly it and similar treatments could become mainstream options.

Gene therapies have also shown promise for serious blood disorders. Researchers were able to dramatically improve the lives of a small cohort of patients with beta thalassemia, which reduces the flow of oxygen through the bloodstream, causing an array of extremely painful side effects. After gene therapy corrected the causative mutation, the number of blood transfusions required by the severely affected patients fell by 74%. Encouragingly, most of the subjects in the trial stopped needing blood transfusions altogether, raising hope that gene therapy could outright cure the excruciating disorder. Scientists have also made progress with hemophilia through gene therapy, reducing bleeding and increasing clotting in patients with both hemophilia A and B.

In one particularly striking example, doctors used gene therapy to save the life of a 7-year-old boy with a rare skin disorder, where a genetic mutation had caused blisters and painful chronic wounds.  A working copy of the disease gene was inserted into stem cells grown from the boy’s skin. These stem cells were grown into sheets of skin in the lab and grafted to more than 80% of the boy’s body. Two years later, his skin now functions properly.

Going Forward

Gene therapies still have very limited uses at very high price points. It can be very challenging to deliver a working copy of a gene to the tissues where it is needed most. That said, physicians are beginning to see effective and lasting treatments – and perhaps even cures – for ailments that have bested them for centuries.

They add to a growing list of genetics-based treatments. For decades, clinicians have been giving patients injections or infusions of proteins their body is unable to produce (think insulin for type I diabetes or clotting factors for hemophilia). In our last Shareable Science, we explored RNA Interference (RNAi) treatments that seek to minimize disease by blocking faulty genes from carrying out incorrect instructions to make malfunctioning proteins. Going one step further, gene therapy seeks to fix the disorder at its source, replacing or directly editing the DNA error.

All told, genomic research expands further and further into the realm of treatment, offering new options to physicians and new hopes for patients. For example, a number of clinical trials using CRISPR-based gene editing tools have recently launched.

As for Mr. Madeux, researchers released a follow-up report for him and three other patients in early September 2018. It showed that some of the individuals who underwent the ZFN treatment did have lower levels of toxic polysaccharides in their body. However, the company behind the treatment, Sangamo Therapeutics, still has a long way to go to show this new method can help these patients in a meaningful, sustainable way. The results show the promise of the treatment — and confirm that promise remains at the very edge of medicine’s reach.

To schedule a media interview with Dr. Neil Lamb or to invite him to speak at an event or conference, please contact Margetta Thomas by email at or by phone: Office (256) 327-0425 | Cell (256) 937-8210