Clinical Trial

Disease: Mucopolysaccharidosis I, MPS I, (NCT02702115)

Disease info:

Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body.

Mutations in the IDUA gene cause MPS I. The IDUA gene provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDUA gene reduce or completely eliminate the function of the IDUA enzyme.

The lack of IDUA enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS I, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder.

This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types.

Individuals with severe MPS I usually begin to show other symptoms  of the disorder within the first year of life, whereas those with the attenuated form may have much milder symptoms that develop later in childhood.

Severe MPS I occurs in approximately 1 in 100,000 newborns, while attenuated MPS I occurs in about 1 in 500,000 newborns.
Official title:
A Phase I / 2, Multicenter, Open-label, Single-dose, Dose-ranging Study to Assess the Safety and Tolerability of SB-318, a rAAV2/6-based Gene Transfer in Subjects With Mucopolysaccharidosis I (MPS I)

United States, California

UCSF Benioff Children's Hospital Oakland, Oakland, California, United States, 94609

Study start:
May. 24, 2017
3 participants
Gene editing method:
ZFN- Zinc Finger Nucleases
Type of edit:
Gene insertion
Alpha-L-iduronidase (IDUA)
Delivery method:
Adeno-associated virus (AAV2/6) - In-vivo
(All three subjects dosed in the study have rolled over to the Long-Term Follow-up Study IVPRP-LT01 (NCT04628871)
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Terminated


The purpose of the study is to evaluate the safety, tolerability of ascending doses of SB-318. SB-318 is an intravenously delivered Zinc Finger Nuclease (ZFN) Therapeutic for genome editing. It inserts a correct copy of the α-L-iduronidase (IDUA) gene into the Albumin locus in hepatocytes with the goal of lifelong therapeutic production of the IDUA enzyme.

The objectives of the study are to provide long term expression of IDUA and improve the current clinical outcome of enzyme replacement therapy (ERT) or hematopoietic stem cell transplantation (HSCT) therapy in subjects with attenuated MPS I, a recessive lysosomal storage disorder that results from mutations in the gene encoding IDUA. SB-318 is a therapeutic for ZFN-mediated genome editing which will be delivered by adeno-associated virus (AAV)-derived vectors. SB-318 is intended to function by placement of the corrective copy of the IDUA transgene into the genome of the subject's own hepatocytes, under the control of the highly expressed endogenous albumin locus, and is expected to provide permanent, liver-specific expression of iduronidase for the lifetime of an MPS I patient.

Last updated: Dec. 28, 2023
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