Study of DNL126 in Pediatric Participants With Mucopolysaccharidosis Type IIIA (Sanfilippo Syndrome Type A)

Key Inclusion Criteria:

• Confirmed diagnosis of MPS IIIA

• For Cohort B1: Have a severe phenotype based on having at least one of thefollowing:

• An older sibling with the same genotype and severe MPS IIIA, in the opinion ofthe investigator

• A definitive genotype indicative of severe MPS IIIA, in the opinion of theinvestigator

• Clinical symptoms of MPS IIIA prior to 28 months of age that, in the opinion ofthe investigator, are indicative of severe MPS IIIA

• For Cohort B2: Are an older sibling of a participant in Cohort B1 (who has alreadybeen confirmed to be eligible for dosing) with MPS IIIA, the same causativegenotype, and who has severe MPS IIIA in the opinion of the investigator

Key Exclusion Criteria:

• Have unstable or poorly controlled medical condition(s) or significant medical orpsychological comorbidity or comorbidities that, in the opinion of the investigator,would interfere with safe participation in the trial or interpretation of studyassessments

• 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 theinvestigator

• For Cohort B only: Are homozygous or compound heterozygous for theN-sulfoglucosamine sulfohydrolase (SGSH) S298P mutation or any other mutation knownto 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 or anakinra within 7 days of screening or intended use ofgenistein or anakinra during the study

• Have a documented likely pathogenic mutation sufficient to cause disease (eg, takinginto account zygosity) of other genes that are known to be associated withdevelopmental delay, seizures, or other significant CNS disorders

• Have clinically significant thrombocytopenia, other clinically significantcoagulation abnormality, significant active bleeding, or require treatment with ananticoagulant or more than two antiplatelet agents

• Contraindication for lumbar punctures

• Contraindication for MRI scan

• Have a clinically significant history of stroke, status epilepticus, head traumawith loss of consciousness, or any clinically significant CNS disease that is notMPS IIIA-related within 3 months of screening

• Have had a ventriculoperitoneal (VP) shunt placed or a clinically significant VPshunt malfunction within 30 days of screening

• Have any clinically significant CNS trauma or disorder, including severe untreatedintracranial hypertension or brain surgery, that, in the opinion of theinvestigator, may interfere with assessment of study endpoints or make participationin the study unsafe