Gene Therapy in Patients With Mucopolysaccharidosis Disease

Mucopolysaccharidosis type VI disease is involved in Lysosomal Storage Disorder. The MPS VI disease is characterized by growth retardation, corneal clouding, cardiac valve disease, organomegaly, skeletal dysplasia, without central nervous system involvement.

Inclusion criteria

• Documented biochemical and molecular diagnosis of MPS VI. Testing for homozygous or compound heterozygous disease-causing mutations of the ARSB gene must have been performed by an accredited laboratory.
• Subjects must be of 4 years of age or older.
• Subjects should have received ERT for at least 12 months before enrolment and should continue to receive ERT until 7-14 days before IMP administration.
• Documented informed consent; willingness to adhere to protocol and to participate to long-term follow-up, as evidenced by written informed consent.

Exclusion criteria

• Subjects unable or unwilling to meet requirements of the study.
• Participation in a clinical study with an investigational drug in the 6 months prior to enrolment in this trial.
• Subjects unable to perform the 6MWT.
• History of severe anaphylactoid reaction to Naglazyme in subjects receiving ERT that could affect the safety (severe reaction is meant to be a respiratory impairment event that is life-threatening).
• Presence of tracheostomy or need of ventilatory assistance.
• Subjects with evidence of progressive myelomalacia that is considered severe enough to require neck surgery in the first six months after enrolment.
• Values of AST or ALT above the upper limit of normal range at baseline 2 (at -5days) evaluations.
• Co-existence of chronic diseases or clinically relevant abnormal baseline laboratory values; infections with hepatitis B, C, or HIV (Baseline 1).
• Systemic corticosteroid therapy or other immunosuppressive/immunomodulating drugs within 2 months prior to IMP administration.
• Female individuals of childbearing age who are pregnant or nursing or unwilling to use effective contraception for at least one year post-IMP administration.
• Fertile male individuals who are unwilling to use male barrier contraceptives such as condom.
• Any other condition that would not allow the subject to complete follow-up examinations during the course of the study and that, in the opinion of the Investigator, would make the subject unsuitable for the study.
• Presence of serum NAB to AAV8 above the limit of detection of the assay (Screening and Baseline 1).
• Presence of serum antibodies anti-ARSB above the upper limit of detection of the assay (antibodies anti-ARSB level >31250 or declared positive at the value of serum dilution 1.10 according to the performed assay) at Screening and Baseline 1.