for people ages 6 months to 18 years (full criteria)
at Oakland, California and other locations
study started
completion around
Principal Investigator
by Paul Harmatz, MD
Headshot of Paul Harmatz
Paul Harmatz



This is a multicenter, open-label, Phase 1/2 study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and exploratory clinical efficacy of DNL126 in participants with Sanfilippo syndrome Type A (MPS IIIA). The core study period is 25 weeks (approximately 6 months) and is followed by a 72-week (approximately 18 month) open-label extension (OLE).

Official Title

A Phase 1/2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)


Mucopolysaccharidosis Type IIIA, Sanfilippo Syndrome, MPS IIIA, Mucopolysaccharidoses, Mucopolysaccharidosis III, DNL126, Optional


You can join if…

Open to people ages 6 months to 18 years

  • Confirmed diagnosis of MPS IIIA
  • Cohort B only: Have a severe phenotype based on an older sibling with the same genotype and severe MPS IIIA based on the opinion of the investigator

You CAN'T join if...

  • Have unstable or poorly controlled medical condition(s) or significant medical or psychological comorbidity or comorbidities that, in the opinion of the investigator, would interfere with safe participation in the trial or interpretation of study assessments
  • Have lost the ability to walk independently, in the opinion of the investigator
  • Are unable to take the majority of nutrition via mouth, in the opinion of the investigator
  • For Cohort B only: Are homozygous or compound heterozygous for the N-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation known to be associated with slow-progressing phenotype
  • Have used any CNS-targeted MPS IIIA enzyme replacement therapy (ERT) (eg, intrathecal SGSH or TfR-mediated SGSH delivery to CNS) within 3 months before Day 1
  • Have a prior history of hematopoietic stem cell transplantation
  • Have a prior history of gene therapy
  • Have used genistein within 30 days of screening or intended use of genistein during the study
  • Have a documented likely pathogenic mutation of other genes that are known to be associated with developmental delay, seizures, or other significant CNS disorders
  • Have clinically significant thrombocytopenia, other clinically significant coagulation abnormality, significant active bleeding, or require treatment with an anticoagulant or more than two antiplatelet agents
  • Contraindication for lumbar punctures
  • Contraindication for MRI scan
  • Have a clinically significant history of stroke, status epilepticus, head trauma with loss of consciousness, or any CNS disease that is not MPS IIIA-related within 3 months of screening
  • Have had a ventriculoperitoneal (VP) shunt placed or a clinically significant VP shunt malfunction within 30 days of screening
  • Have any clinically significant CNS trauma or disorder, including severe untreated intracranial hypertension or brain surgery, that, in the opinion of the investigator, may interfere with assessment of study endpoints or make participation in the study unsafe


  • UCSF Benioff Children's Hospital Oakland accepting new patients
    Oakland California 94609 United States
  • University of North Carolina at Chapel Hill accepting new patients
    Chapel Hill North Carolina 27514 United States

Lead Scientist at UCSF

  • Paul Harmatz, MD
    Dr. Paul Harmatz is a gastroenterologist who specializes in mucopolysaccharidoses (MPS) and other lysosomal storage diseases (genetic disorders in which a lack of certain enzymes results in progressive damage to cells and organ systems). He leads a team of specialists who diagnose and care for patients with these rare diseases, offering therapies such as weekly enzyme infusion.


accepting new patients
Start Date
Completion Date
Denali Therapeutics Inc.
Phase 1/2 research study
Study Type
Expecting 16 study participants
Last Updated