AAVance: A Clinical trial Investigating a Potential Therapy for Patients with MPS IIIA

The goal of the therapy is to show improved or stabilized neurodevelopmental status of MPS IIIA patients by allowing the brain cells to secrete the missing enzyme. Development under treatment will be compared to development based on natural history studies. The trial will enroll 20 patients at eight sites in the U.S. and Europe.

MPS IIIA (Sanfilippo A Syndrome)

MPS IIIA, or Sanfilippo syndrome type A, is a rare inherited lysosomal storage disorder characterized by progressive neurodegeneration and early death. MPS IIIA is caused by mutations in the N-sulfoglucosamine sulfohydrolase (SGSH) gene that encodes an enzyme called Heparan-N-sulfamidase necessary for breakdown of a large sugar molecule called heparan sulfate (HS) in cells. As heparan sulfate accumulates, it affects the normal functions of the body, in particular the brain. Signs and symptoms usually become apparent in early childhood and include speech problems, developmental delays, challenging behaviors, extreme hyperactivity, and poor sleep.

Purpose of the AAVance Clinical Trial

A single-arm trial evaluating the safety and effectiveness of a one-time delivery of a recombinant adeno-associated virus vector rh.10 carrying the SGSH gene, in patients with Mucopolysaccharidosis IIIA (MPS IIIA).
Investigational Therapeutic:
Recombinant adeno-associated virus (AAV) rh.10 carrying the N-sulfoglucosamine sulfohydrolase (SGSH) gene (LYS-SAF302)
Study Type:
find a trial location

What is LYS-SAF302 Gene Therapy?

The Lysogene/Sarepta partnered investigational therapy, LYS-SAF302, is being evaluated in the AAVance study as an approach to supplement the faulty SGSH gene with a healthy copy of the gene. By supplementing the defective gene it is hoped that the body will start making sufficient quantities of enzyme (Heparan-N-sulfamidase ) and therefore slow or halt the progression of the disease.
Normal SGSH gene is inserted into the AAVrh.10 virus
The gene therapy is administered to your child
The gene therapy is taken into the brain cells.
The gene therapy makes the enzyme, SGSH, in the brain cells and the enzyme is secreted throughout the brain.

Who is Eligible?

Children with documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
Children with a cognitive development quotient (DQ) score of 50 and above, using a test called the Bayley Scales of Infant and Toddler Development (BSID-III).

There are additional requirements for participation. For more information about potential inclusion in this study, please contact PatientAdvocacy@Lysogene.com.


Frequently Asked Questions

Who is Eligible?
• Children with documented MPS IIIA diagnosis based on genotyping confirming the SGSH gene mutations
• Children with a cognitive development quotient (DQ) score of 50 and above, using a test called the Bayley Scales of Infant and Toddler Development (BSID-III).
• There are additional requirements for participation. For more information about potential inclusion in this study, please contact PatientAdvocacy@Lysogene.com or check clinicaltrials.gov.
How many children will be enrolled in this study and where is it being run?
20 patients are planned to be enrolled in this study. We have clinical trial sites in the United States and Europe. Patients from other geographies may also be considered for the trial.
What is a cognitive DQ score?
A cognitive developmental quotient or DQ is an indication of a child’s maturity and growth across a range of competencies relative to their age. This study uses the Bayley Scales of Infant and Toddler Development (BSID-III), to measure a cognitive DQ number.
Why is the gene therapy administered directly to the brain?
Our brains are protected by what is known as the 'blood-brain barrier'. This stops unwanted substances in the blood from entering the brain and limits the amount of gene therapy entering the brain when administered by normal injection. For
this reason, the gene therapy is given by a surgeon under general anesthesia. The gene therapy enters the brain cells and is able to initiate the production of enzyme and limit the neurological effects of the disease on the brain.
Why is immunosuppressive treatment part of this study?
Children in this study will also receive an immune suppression in order to prevent any potential immune response against the AAVrh10 virus or against the protein expressed from the administered gene, which could potentially impair overall efficacy. The duration of immune suppression will be discussed with the study investigator.
When can we expect to see possible changes after the gene therapy administration?
It is hoped that the gene therapy will stop the progression of the disease in a child receiving treatment. Children will be monitored very closely by means of examinations, about every six months, allowing us to assess the nervous system through neurocognitive tests and brain imaging.
What does participation involve?
The first step is a discussion with one of the study sites, where investigators will determine your child's eligibility to participate in the study. If eligible, the dosing of the investigational medication will take place up to 8 weeks after the initial baseline visit. After dosing your child will be followed up for an initial period of 2 years. This period is followed by an additional 3-year period to conduct long-term efficacy analysis and safety assessment.

• During the screening period of up to 8 weeks, your child will be visiting the clinical site once and separately the surgical site once prior to procedure to confirm eligibility for the trial

• Your family will be relocated to the surgical site one week prior to the surgery and be asked to remain in the surgical site area for about 2 weeks post-surgery

• Up to 7 days before surgery your child will start immunosuppressive treatment

• After the surgery there will be visits with the clinical site at 1 month post procedure and then every three months starting at month 6 for a brief check-up, blood and urine tests. Additional development testing will be conducted every 6 months starting at month 6

• A meeting with the neurosurgeon will be held at month 3 post procedure

• You can learn more about all of the requirements and activities in this clinical trial from the study doctor.
What risks are associated with this study?
As with all clinical studies, there can be risks associated with possible side effects of taking the study drug and with the standard medical tests carried out as part of the study at each visit. Information on the possible side effects your child may experience in the study is available in the consent form and should be discussed with your study doctor.
What are some benefits to being a part of this clinical trial?
The potential benefits of LYS-SAF302 in patients with MPS IIIA are unknown. Even if you do not benefit from being in this study, we might learn something that could advance research and help others.
Will the gene therapy need to be repeated?
Gene therapy is intended to be a one-time treatment. We know, from pre-clinical experiments that when enzyme is present in the brain the diseased brain cells return to normal function i.e. they break down heparan sulfate. This effect in animal experiments is long-lasting, but we don’t know yet whether it is "for life."
Will the costs of my participating in this study be reimbursed?
Generally, reasonable costs associated with participation in the study will be prepaid or reimbursed by Lysogene in accordance with the approved travel policy for the study procedures performed as part of the study. Information will be provided by the study site.

Find a Trial Location

Find the nearest clinical trial site. If you are interested in this study, please contact PatientAdvocacy@Lysogene.com or your healthcare provider.
View list of locations
Armand Trousseau Public Hospital
Paris, France 75012
Contact: Bénédicte Heron, MD
Principal Investigator: Bénédicte Heron, MD
Status: Recruiting
University Medical Center Hamburg-Eppendorf
Hamburg, Germany 20246
Contact: Nicole Muschol, MD
Principal Investigator: Nicole Muschol, MD
Status: Not yet recruiting
Amsterdam UMC
Amsterdam , Netherlands 1000
Principal Investigator: Frits Wijburg, MD
Status: Recruiting
United States
Baylor college of medicine / Texas children's hospital
Houston, Texas 77030
Contact: Lisa Emrick, MD
832-825-1717 emrick@bcm.edu
Principal Investigator:
Status: Recruiting
United States
Weill Cornell Medical College
New York, New York 10065-4897
Contact: Department of Genetic Medicine
646-962-2672 cora@med.cornell.edu
Principal Investigator:
Status: Recruiting
United States
University of Minnesota
Minneapolis, Minnesota 55455
Contact: Brenda Diethelm-Okita, MPA
612-625-1594 dieth001@umn.edu
Principal Investigator: Chester Whitley, MD
Status: Recruiting
United States
CHOC Children's
Orange, California 92868
Contact: Nina Movsesyan
Principal Investigator: Raymond Wang, MD
Status: Recruiting

Still have questions about whether this trial is right for you and your family?

Lysogene's Patient Advocacy Team is available to answer your questions. Email PatientAdvocacy@lysogene.com. Or visit clinicaltrials.gov for more information, including a list of sites that are enrolling patients.