Sangamo Therapeutics shared some big news about the search for Mucopolysaccharidosis II (MPS II) treatment. They reported that they have, for the very first time, used experimental in vivo gene therapy to treat a patient with MPS II, in phase 1/2 clinical trial.
MPS II, also called Hunter syndrome, is a rare and progressively debilitating condition, which usually affects males. It occurs in individuals with a shortage of iduronate 2-sulfatase, an enzyme that helps break down large sugar molecules. It may be identified in children ages 2-4, due to distinct physical traits, such as a broad nose, enlarged tongue, full lips, and round cheeks. It also leads to serious symptoms, such as respiratory problems caused by narrowed airways, enlarged liver and spleen, inguinal hernia, macrocephaly, and a build up of fluid in the brain, called hydrocephalus. Symptom severity varies between patients. Prognosis has improved, due to advancements in treatments for cardiac and respiratory symptoms. Still, for many, MPS II can be life-threatening. To learn more about this rare disorder, click here.
Sangamo, a pharmaceutical company, set out to correct the genetic mutation that leads to this disorder. The company uses zinc finger nuclease (ZFN) gene editing technology to go in and remove the mutated gene, and replace it with a corrected version of the same gene. Sangamo is specifically focusing on liver cells, in order to let the body create a stable supply of the missing enzyme for the rest of the patient’s life.
Sangamo’s CEO, Sandy Macrae, says that this is the first time that a MPS II patient has been given a treatment that edits the DNA of living cells in the body.
The therapy is called SB-913. Doctors administer the ZFN treatment intravenously. The ZFN, along with the fixed version of the cell, make their way to the patient’s liver. They bind to the target cells, with DNA instructions that unlock liver cells. The ZFN treatment then binds to the unlocked liver cells, and cuts out a precise portion of the DNA. Then, it takes advantage of the natural DNA repair processes in order to stick in the corrected version of the gene, which helps the body produce the missing enzyme.
This is a major improvement on the current treatments, which still leave patients vulnerable to worsening damage to vital organs. Even with the existing treatments, patients with MPS II often do not make it 20, because of respiratory problems. Gene editing can change that.
Sangamo has two other clinical trials evaluating their in vivo gene editing tool for a related condition called MPS I (or Hurler syndrome) and hemophilia B. All of these trials are targeting the albumin gene in the liver. The trials have received both Fast Track and Orphan Drug designations from the FDA. FDA has also given the Rare Pediatric Disease designation to the therapies for MPS I and MPS II. They are working closely alongside the FDA and NIH to make sure the study is done responsibly.
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