Date: 2018-04-04
Type of
information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Molecular Therapy
Company: Sangamo Therapeutics (USA - CA)
Product: SB-913 (adeno-associated virus serotype 2/6 (rAAV2/6) vectors encoding zinc finger nucleases (ZFNs) and the human iduronate 2-sulfatase (hIDS) gene)
Action
mechanism:
- gene therapy/genome editing product. Without iduronate-2-sulfatase (IDS), people with mucopolysaccharidosis type II (MPS II) suffer debilitating buildup of toxic carbohydrates in cells throughout their body. Approximately one in 100,000 to one in 170,000 people are born with MPS II. Many people with MPS II receive weekly infusions of enzyme replacement therapy (ERT), the current standard-of-care treatment. Within a day of receiving ERT, however, IDS quickly returns to near undetectable levels in the blood.
- SB-913 makes use of Sangamo's zinc finger nuclease (ZFN) genome editing technology to insert a corrective gene into a precise location in the DNA of liver cells. To restrict editing to liver cells, the ZFNs and the corrective gene are delivered in a single intravenous infusion using AAV vectors that target the liver. The ZFNs enter the cells as inactive DNA instructions in a format designed only for liver cells to unlock. Once "unlocked", the ZFNs then identify, bind to and cut the DNA in a specific location within the albumin gene. Using the cells' natural DNA repair processes, liver cells can then insert the corrective gene for IDS at that precise location.
Disease: mucopolysaccharidosis type II (Hunter's syndrome)
Therapeutic
area: Rare diseases - Genetic diseases - Hematological diseases
Country:
Trial
details:
Latest
news:
- • On April 4, 2018, Sangamo Therapeutics announced the publication of preclinical murine study data from the company's in vivo genome editing program for mucopolysaccharidosis Type II (MPS II) in the April 2018 issue of Molecular Therapy (Laoharawee et al., Dose-Dependent Prevention of Metabolic and Neurologic Disease in Murine MPS II by ZFN-Mediated In Vivo Genome Editing, Molecular Therapy (2018) Vol 26, Issue 4, P1127-1136).
- In the study, in a mouse model of MPS II, zinc finger nuclease (ZFN)-mediated genome editing of cells in the liver resulted in expression of therapeutic levels of iduronate 2-sulfatase (IDS), an enzyme MPS II patients lack, and in the prevention of metabolic and neurological disease symptoms. The work was conducted in collaboration with the laboratory of Dr. Scott McIvor at the University of Minnesota's Center for Genome Engineering.
- Male MPS II model mice between six and nine weeks of age were injected with one of three increasing dose levels of a genome editing treatment consisting of AAV2/8 vectors encoding a pair of ZFNs and a corrective human IDS (hIDS) gene. The treatment was designed to integrate the hIDS gene in a precise location within the albumin gene in liver cells. Treated mice, at both one and four-months after injection, exhibited dose-dependent expression of IDS enzyme in blood and peripheral tissues, including the spleen, kidney, lung, heart, and skeletal muscle. Enzyme expression in liver cells reached levels greater than 200-fold higher than in wild-type mice. In all tested peripheral organs, treatment at the highest dose resulted in greater than 95% reduction in glycosaminoglycan (GAG) substrate levels. Importantly, treatment with Sangamo's genome editing therapy at the highest dose level also prevented the development of neurocognitive deficit in the young MPS II model mice, as measured by the Barnes Maze test.
- Sangamo is currently evaluating in the CHAMPIONS Study, a Phase 1/2 clinical trial assessing the potential safety and efficacy of SB-913 in up to nine adult males with attenuated MPS II.
Is
general: Yes
