Lysosomal Storage Disorders

Lead Indication Approach Program Research Preclinical Phase 1/2 Phase 3
ZFN (insert) SB-318
Research Phase complete
Preclinical Phase complete
Phase 1/2 Phase in progress
Phase 3 Phase not started

MPS I (Scheie, Hurler-Scheie and Hurler syndromes) is a lysosomal storage disorder caused by a deficiency of the enzyme alpha-L iduronidase (IDUA) and results in the toxic buildup of glycosaminoglycans (GAGs). Sangamo Therapeutics has an open IND application for SB-318 and is initiating an open-label, dose-escalating Phase 1/2 clinical trial to assess the safety, tolerability and preliminary efficacy of the treatment. SB-318 uses ZFN-mediated in vivo genome editing to place a normal functioning copy of the IDUA gene under the control of the strong albumin promoter in the patient’s liver.  This enables the liver to produce and secrete active IDUA into the bloodstream to be taken up by other tissues.

ZFN (insert) SB-913
Research Phase complete
Preclinical Phase complete
Phase 1/2 Phase in progress
Phase 3 Phase not started

MPS II (Hunter syndrome) is a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS) that results in the buildup of glycosaminoglycans (GAGs). Sangamo Therapeutics has an open IND application for SB-913 and is initiating an open-label, dose-escalating Phase 1/2 clinical trial to assess the safety, tolerability and preliminary efficacy of the treatment. SB-913 uses our ZFN-mediated in vivo genome editing to place a normal functioning copy of the IDS gene under the control of the strong albumin promoter in the patient’s liver. This enables the liver to produce and secrete active IDS into the bloodstream to be taken up by other tissues.

About MPS I and MPS II

Mucopolysaccharidosis Type I (MPS I) and MPS II are inherited metabolic disorders known as lysosomal storage disorders (LSDs). They are caused by mutations in genes encoding enzymes that break down unwanted substances in cells. Lack of these enzymes leads to the toxic build-up of these substances. The resulting cell damage can lead to serious health problems.

MPS I

MPS I (Scheie, Hurler-Scheie and Hurler syndromes) is caused by mutations in the gene encoding the alpha-L-iduronidase (IDUA) enzyme which is required for the degradation of glycosaminoglycans (GAGs). The inability to degrade GAGs leads to their accumulation throughout the body. Depending on the severity of the mutations and degree of residual enzyme activity, affected individuals may develop enlarged organs, joint stiffness, skeletal deformities, corneal clouding, hearing loss and cognitive disability.

MPS II

MPS II (Hunter syndrome) is a progressive disorder that primarily affects males and is caused by mutations in the gene encoding the iduronate-2-sulfatase (IDS) enzyme which is also required for the degradation of GAGs. Children with MPS II begin showing symptoms of developmental delay by age 2 – 3 years. Depending on the severity of the mutation and degree of residual enzyme activity, affected individuals may experience delayed development and develop enlarged internal organs, cardiovascular disorders, stunted growth, skeletal abnormalities and hearing loss.

LSDs affect approximately 1 in every 5,000 live births

All disease statistics are according to the National MPS Society.

2,000

MPS I patients in the U.S

Three forms of MPS I, in order of increasing severity, include Scheie, Hurler-Scheie and Hurler syndromes.

500

Approximate number of MPS II patients in the U.S.

One in 100,000 male births in the U.S. will result in MPS II.

Our Therapeutic Approach

SB-318 for MPS I and MPS-913 for MPS II 

SB-318 (MPS I) and SB-913 (MPS II) are designed to provide stable, continuous production of the enzymes IDUA (MPS I) or IDS (MPS II) for the lifetime of the patient. Sangamo’s ZFN-mediated in vivo genome editing approach makes use of the albumin gene locus, a highly expressing gene in the DNA of a patient’s liver cells that can be edited with ZFNs to accept and express therapeutic genes. The approach is designed to enable the liver to permanently produce circulating therapeutic levels of a corrective enzyme product. Ultimately, the target population for this approach will include pediatric patients for whom it is important to be able to produce stable levels of therapeutic protein for their lifetime. With such a large capacity for protein production (approximately 15g/day of albumin), targeting and co-opting only a very small percentage of the albumin gene’s capacity could potentially produce therapeutically relevant levels of IDUA (MPS I) or IDS (MPS II) with no significant effect on albumin production.

Clinical Trials

Clinical Trials

In 2017 Sangamo is conducting Phase 1/2 clinical trials to evaluate safety, tolerability and preliminary efficacy in MPS I and MPS II. Please visit the Clinicaltrials.gov webpage to learn more about our clinical trials.

Learn More

Presentations + Publications

In vivo genome editing of the albumin locus as a platform for protein replacement therapy

Rajiv Sharma, Xavier M. Anguela, Yannick Doyon, Thomas Wechsler, Russell C. DeKelver, Scott Sproul, David E. Paschon, Jeffrey C. Miller, Robert J. Davidson, David Shivak, Shangzhen Zhou, Julianne Rieders, Philip D. Gregory, Michael C. Holmes, Edward J. Rebar and Katherine A. High
BLOOD, 8 OCTOBER 2015 x VOLUME 126, NUMBER 15

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