Sanfilippo syndrome type A, also called mucopolysaccharidosis type IIIA (MPS IIIA), is a rare, inherited condition that affects the brain and nervous system. Children with MPS IIIA are missing a working copy of an enzyme the body needs to break down a complex sugar molecule called heparan sulfate. When this sugar builds up inside cells, especially in the brain, it progressively damages how children think, learn, and develop. Many children with MPS IIIA develop normally at first, then start to lose language, movement, and thinking skills they had already gained.
Until recently, care for MPS IIIA focused only on managing symptoms because there was no treatment that could change the course of the disease itself.
In September 2026, the FDA approved Fayuvi (rebisufligene etisparvovec-hopf) as the first gene therapy for MPS IIIA. Fayuvi is a one-time IV (given into a vein) infusion. It's designed to deliver a working copy of the gene a child's body is missing so that cells can start making the enzyme on their own.
This article covers how Fayuvi works, who it's approved for, how it's given, and what clinical studies have found so far. You may also be interested in reading about Fayuvi side effects and interactions.
How Does Fayuvi Work for MPS IIIA?
MPS IIIA happens because of changes (mutations) in a gene called SGSH. This gene normally tells the body how to make an enzyme called sulfamidase. Sulfamidase's job is to help break down heparan sulfate, a sugar molecule found throughout the body, including in the brain.
Without enough working sulfamidase, heparan sulfate builds up inside cells instead of being broken down and cleared away. Over time, this buildup damages brain cells and interferes with normal development.
Fayuvi is built on a harmless, modified virus called an adeno-associated virus serotype 9 (AAV9). This type of virus is commonly used in gene therapy because it can deliver genetic material into cells without causing illness, and it can reach tissue throughout the body, including the brain. Fayuvi uses this AAV9 vector to carry a working copy of the SGSH gene into a child's cells. Once inside, cells can use this copy to start making sulfamidase, allowing the body to break down heparan sulfate again.
Because Fayuvi is given once, as a single infusion, it's designed to provide ongoing production of the enzyme going forward, rather than needing to be given repeatedly like some other treatments for lysosomal storage conditions.
Is Fayuvi Right for My Child?
Fayuvi is approved for the treatment of neurological manifestations of MPS IIIA in pediatric patients with preserved neurodevelopmental function. In other words, it's intended for children whose thinking and developmental skills haven't yet declined to an advanced stage from the disease.
A diagnosis of MPS IIIA is typically confirmed through enzyme activity testing and genetic testing that identifies two altered copies of the SGSH gene. Your child's health care provider will also want to assess current developmental and cognitive function as part of deciding whether Fayuvi is a good option.
Before treatment, your child's health care provider will also test for antibodies against the AAV9 vector itself. Some children have natural antibodies to AAV9, often from prior exposure to similar viruses. Fayuvi isn't recommended for children with high levels of these antibodies because the antibodies could prevent the gene therapy from reaching its target cells effectively.
How Is Fayuvi Given?
Fayuvi is given as a single, slow IV infusion over about one hour. It isn't given by mouth, and it isn't repeated. The dose is based on your child's body weight.
Because Fayuvi can affect liver health, your child's health care provider will check liver test results (and platelet counts) before the infusion. Starting the day before the infusion, your child will take an oral corticosteroid medicine to help lower the chance of liver-related side effects. This is typically continued for at least eight weeks, then slowly tapered down over at least four more weeks, based on how your child's liver tests look along the way.
After the infusion, your child's health care provider will continue to check liver test results regularly (weekly at first, then every two weeks) until at least two weeks after the corticosteroid taper finishes. They will likely check platelet counts weekly for the first month, then monthly for six months. These follow-up visits are an important part of using Fayuvi safely, so it's worth planning for them in advance.
Fayuvi is only given at specialized treatment centers with experience in gene therapy and the ability to manage infusion reactions if they occur.
How Was Fayuvi Studied for MPS IIIA?
Fayuvi's approval was based on an ongoing clinical study (referred to here as the pivotal study) along with a long-term follow-up study that continued to track children after they finished the main study period.
Because MPS IIIA is so rare and the disease worsens steadily without treatment, researchers didn't compare Fayuvi to a placebo (a look-alike treatment with no medicine in it). Instead, children who received Fayuvi were compared with a separate group of children with MPS IIIA who didn't receive treatment, drawn from historical medical records (called a natural history control group). This approach is sometimes used in rare disease research, when a large enough group of untreated patients for a traditional placebo-controlled trial wouldn't be feasible or ethical.
The main group used to measure how well Fayuvi worked included 17 children who received the recommended dose and were either 2 years old or younger or older than 2 years with cognitive skills that hadn't declined too far already (based on a standard developmental test, explained below). At the start of the study, these children were, on average, about 22 months old (ranging from 3 months to just under 3 years) and weighed about 13 kg (29 lbs) on average. About two-thirds were boys, all were White, and about 1 in 8 were Hispanic or Latino.
The comparison group of 27 untreated children was, on average, about 38 months old at the time their records were reviewed. About 3 in 4 were boys. Race and ethnicity weren't recorded for about half of this group; among those with data available, about half were White.
Researchers measured thinking and developmental skills using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), a standardized test used in young children. Specifically, they looked at the cognitive subtest, in which a child scores from 0 to 91 based on skills such as memory, problem-solving, and object exploration, with higher scores meaning more developed skills. At the start of the study, children who went on to receive Fayuvi had an average Cognitive score of about 48 (out of a possible 91), while children in the untreated comparison group averaged about 55.
What Are the Main Benefits of Fayuvi Based on Studies?
Researchers tracked how each child's Bayley-III Cognitive score changed between 24 and 60 months (2-5 years) of age, comparing children treated with Fayuvi to the untreated natural history group.
On average, children treated with Fayuvi gained about 16 points on the Cognitive scale over this period. Children in the untreated comparison group lost about 7.6 points, on average, reflecting the cognitive decline that's typical as MPS IIIA progresses without treatment. That's a difference of about 23.5 points favoring children treated with Fayuvi. Researchers considered this difference meaningful and not likely to be due to chance.
In practical terms, this means that children treated with Fayuvi tended to gain or hold on to developmental skills during this period, while children who didn't receive treatment tended to lose skills they'd already developed.
Your child's results may differ from what was seen in clinical studies.
Are There Additional Potential Benefits of Fayuvi Based on Studies?
Beyond the main cognitive measurement above, researchers also tracked a biomarker (a measurable sign of disease activity) called cerebrospinal fluid heparan sulfate (CSF HS). This is the level of the built-up sugar molecule described earlier, measured in the fluid that surrounds the brain and spinal cord.
Within the first month after treatment, CSF HS levels dropped substantially, and this reduction was generally sustained through at least two years of follow-up. By two years after treatment, the large majority of children maintained at least a 50% reduction in CSF HS compared with where they started. While this measurement doesn't directly describe how a child feels or functions day to day, researchers use it as a sign that the gene therapy is working as intended, by helping the body clear out the built-up substance that drives the disease.
Separately published research following children treated with Fayuvi (under its earlier research name, UX111) also reported gains across specific areas of development beyond the single Cognitive score, including receptive and expressive communication (understanding and using language) and fine and gross motor skills (small and large movements), when compared with the expected course of untreated MPS IIIA.
Your child's results may differ from what was seen in these studies.
How Long Were the Studies? Is There Longer-Term Data?
Children in the main study were followed for 24 months and then had the option to continue into a separate long-term follow-up study. Across both studies, children treated with Fayuvi have now been followed for a median of about 4.2 years, with some children followed for close to eight years. Most of the children in the main efficacy group have now reached at least 5 years of age, giving researchers a meaningful look at how the gene therapy's effects hold up over time, rather than just in the months right after treatment.
Separately published data pooling all children treated with Fayuvi across every dose level studied, including some treated with lower doses earlier in development, reported a similar pattern: reductions in CSF HS that were sustained through a median follow-up of more than 3.5 years for most participants, with continued stabilization or improvement in developmental skills, including in some children who were older or had more advanced disease at the time of treatment.
What Are Other Unique Considerations to Be Aware Of?
Fayuvi is a one-time treatment, which is different from many other therapies for rare metabolic conditions that require ongoing, repeated dosing. Because the goal is for the gene therapy to keep working over your child's lifetime, there's currently limited data on what would happen if a child needed another dose or another AAV9-based gene therapy later on.
After treatment, small amounts of the Fayuvi vector can be temporarily present in your child's bodily fluids and waste (called vector shedding). Extra precautions around handling diapers, bodily fluids, and hand hygiene are recommended for about three months after the infusion to reduce the chance of the vector being passed to others.
What Do I Need to Do to Get Fayuvi? What Kind of Doctor Prescribes It?
Fayuvi is only available through specialized treatment centers with experience administering AAV-based gene therapies and the staff and equipment needed to monitor for and manage infusion reactions. Your child's metabolic specialist or geneticist can help coordinate a referral to one of these centers, which will also handle the pretreatment testing (including the AAV9 antibody test described earlier) and the follow-up monitoring schedule.
Is There Any Cost Assistance Available?
Fayuvi is a complex, specialized treatment, and cost and insurance coverage are often major questions for families considering it. Ultragenyx Pharmaceutical Inc., the maker of Fayuvi, offers a patient support program to help families understand their insurance coverage, explore financial assistance options, and navigate the steps involved in getting treatment, regardless of the type of insurance a family has. You can learn more by visiting Ultragenyx's patient support page or calling 888-756-8657.