Gene therapy used to cure rare Hunter Syndrome

By CINDY JIANG | February 1, 2018

Like flying cars and underwater cities, tampering with DNA once seemed to be an impossible feat that existed only in futuristic tales.

In recent times, however, the abundance of technological advances make this process appear much more attainable. After all, if a cell phone can be guarded by a scan of facial features, the ability to alter DNA should be just around the corner.

Indeed, the scientific community has been taking strides to make gene-editing a reality.

In mid-November, U.S. scientists used gene-editing tools on a human for the first time when a 44-year-old patient named Brian Madeux underwent a medical procedure meant to cure his Hunter syndrome.

Hunter syndrome is also known as mucopolysaccharidosis II (MPS II), and it is an inherited genetic disorder resulting from a missing or a malfunctioning enzyme. Though the syndrome is quite rare, it is considerably detrimental to a patient’s health, since particular molecules accumulate in excess from the lack of enzymes to metabolize them.

Such an accumulation leads to gradual effects on an individual’s appearance, mental development, organ function and physical abilities. Frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues, and brain and thinking problems are just some of the symptoms that are associated with Hunter syndrome.

The procedure to cure Hunter syndrome was carried out by researchers at the University of California, San Francisco’s Benioff Children’s Hospital in Oakland, Calif. It involved introducing a multitude of molecular units to Madeux via an IV.

Although the CRISPR tool has been enjoying its time in the limelight, scientists decided to treat Madeux with a different type of editing technology called zinc finger nucleases (ZFNs). The editing process is comprised of three parts: a corrective gene and two zinc finger proteins, all of which are transported into the body by a virus.

Once in the liver, the zinc finger proteins are in charge of cutting the DNA so that the corrective gene may insert itself into the sequence.

Sangamo Therapeutics is the company that invested in the experiment. Its president, Sandy Macrae, explained that Madeux’s trial is essentially the first of its kind in its attempt to alter DNA in vivo.

“This is opening up a whole new field of medicine. You can imagine all the diseases that now become possible to treat when you can put in a new copy of the gene, or turn it up or turn it down,” Macrae said in a press release.

Madeux will be monitored in the following months. Progress may be apparent in just a month, but definitive conclusions should only come after about three months. Should the trial be a success, it would serve as a monumental milestone for the field of gene therapy.

Macrae aims to use the potential success of the procedure to provide a cure for children affected by Hunter syndrome. The prospects wouldn’t be as promising for older patients because they might have already arrived at a state in which certain conditions cannot be reversed.

However, the possibility of a cure doesn’t imply that the entire procedure is not without risk. In fact, one of the most prominent dangers of gene-editing is an “off-target” edit. Such an occurrence could induce cancer under the worst-case scenarios.

“It’s kind of humbling [to be the first to test this]. I’m willing to take that risk. Hopefully it will help me and other people,” Madeux said.

Despite current uncertainty, there is no doubt that this process possesses a lot of potential to do good in the world, and should Hunter syndrome find a cure through gene-editing, other individuals suffering from heritable disorders like hemophilia and sickle cell disease could find a reprieve in this novel form of gene therapy.

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