UCSF Benioff Children’s Hospital Oakland Has First Patient in Landmark Clinical Trial Evaluating "In Vivo" Genome Editing for Rare Genetic Disorder

UCSF Benioff Children’s Hospital Oakland Has First Patient in Landmark Phase 1/2 Clinical Trial Evaluating In Vivo Genome Editing for MPS II

Oakland/Richmond, CA (Nov. 15, 2017) – UCSF Benioff Children’s Hospital Oakland and Sangamo Therapeutics, Inc. today announced treatment of the first patient in the Phase 1/2 clinical trial ("the CHAMPIONS study") evaluating SB-913, an investigational in vivo genome editing therapy for people with mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome.

The trial, being lead in at the hospital by UCSF Benioff Oakland’s Paul Harmatz, M.D., involves an adult patient who has previously participated in other clinical trials for MPS II and who is a long-term patient of Dr. Harmatz.

The clinical trial aims to treat MPS II by using genome editing to insert a corrective gene into a precise location in the DNA of liver cells with the goal of enabling a patient's liver to produce a lifelong and stable supply of an enzyme he currently lacks.

 “We are proud to be part of this groundbreaking trial and it is our hope that the gene editing therapy will produce benefits to our patient and other MPS patients that will greatly contribute to an improved quality of life. We are grateful to our patient Brian for being the first person to participate in the trial,” said Dr. Harmatz, M.D., a pediatric gastroenterologist and a principal investigator for the CHAMPIONS study at the UCSF Benioff Children's Hospital Oakland.

"For the first time, a patient has received a therapy intended to precisely edit the DNA of cells directly inside the body. We are at the start of a new frontier of genomic medicine," said Dr. Sandy Macrae, CEO of Sangamo Therapeutics.

Without that enzyme, called iduronate-2-sulfatase (IDS), people with 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.

"Even with regular infusions of ERT, which has markedly improved functional health outcomes, patients endure progressive damage to heart, bones and lungs. Many patients with MPS II die of airway obstruction, upper respiratory infection or heart failure before they reach the age of 20," said Dr. Harmatz.

The CHAMPIONS study, which is also screening subjects at hospitals specializing in the care of patients with MPS II, including hospitals in Chapel Hill, Chicago, Minneapolis and Philadelphia, is an open-label clinical study designed to assess the safety, tolerability and preliminary efficacy of the SB-913 investigational genome editing therapy in up to nine adult males with MPS II.

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.

The ability to permanently and precisely integrate the therapeutic IDS gene into the DNA differentiates this in vivo genome editing approach from conventional AAV cDNA gene therapy and from lenti- or retroviral-based gene therapies that insert genes randomly into the genome.

UCSF Benioff Children’s Hospital Oakland’s/CHORI’s gastroenterology research group, under the direction of Dr. Paul Harmatz, is focused on translational and clinical research on the treatment of lysosomal storage diseases focused primarily on the mucopolysaccharidoses.

The mucopolysaccharidoses (MPS) are a group of 11 rare genetic disorders in the lysosomal storage disease (LSD) family, each caused by the absence or reduced function of lysosomal enzymes needed to break down glycosaminoglycans (GAGs). GAGs are long chains of carbohydrate constituents of bone, cartilage, and connective tissue. In the absence of lysosomal enzyme function, these GAGs collect in the cells and connective tissues and result in progressive cellular damage and organ system dysfunction. The mucopolysaccharidoses share many clinical features but have varying degrees of severity. Treating these patients has depended on medical and surgical care, with hematopoietic stem cell transplantation as the only cure.

Since 2003, enzyme replacement therapy (ERT) has been approved for MPS I, II  and VI to provide specific therapy administered intravenously. Dr. Harmatz participated in the clinical trials for MPS II and VI that led to FDA approval. Dr. Harmatz lead one of only two US sites that participated in a longitudinal, multicenter, multinational natural history study for MPS IVA or Morquio A. He was also PI of one the US sites for the phase 3, randomized, placebo controlled trial of enzyme replacement therapy that lead to the  U.S. Food and Drug Administration (FDA) has approval of VIMIZIM™ (elosulfase alfa) for patients with MPS IVA (Morquio A syndrome). In addition to these trials, Dr. Harmatz and his colleagues have participated in the NIH-sponsored Lysosomal Disease Network studies and enrolled patients into a longitudinal study of brain disease in MPS I and II.

About UCSF Benioff Children’s Hospital Oakland
UCSF Benioff Children’s Hospital Oakland (formerly Children’s Hospital & Research Center Oakland) is a premier, not-for-profit medical center for children in Northern California, and is the only hospital in the East Bay 100% devoted to pediatrics. UCSF Benioff Children’s Hospital Oakland is a national leader in many pediatric specialties and is one of only five ACS Pediatric Level I Trauma Centers in the state. The hospital has one of largest pediatric intensive care units and pediatric rehabilitation units in Northern California. It is also a leading teaching hospital with an outstanding pediatric residency program and a number of unique pediatric subspecialty fellowship programs. UCSF Benioff Children’s Hospital Oakland’s research arm, Children’s Hospital Oakland Research Institute (CHORI), is internationally known for its basic, translational and clinical research.

About Sangamo Therapeutics
Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic therapies that transform patients' lives using the Company's industry leading platform technologies in genome editing, gene therapy, gene regulation and cell therapy. For more information about Sangamo, visit

PublishedNovember 2017


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