Spruce Reports Positive Long-Term Data for MPS IIIB ERT

Rare Daily Staff

Spruce Biosciences has reported long-term clinical data suggesting its experimental enzyme replacement therapy, tralesinidase alfa, may offer the first disease-modifying approach for Sanfilippo syndrome type B, a rare and fatal pediatric neurodegenerative disorder with no approved treatments.

The findings, presented at the 18th International MPS & Related Lysosomal Diseases Symposium in Florence, Italy, show that weekly administration of tralesinidase alfa (TA-ERT) directly into the brain led to sustained biochemical and clinical effects over up to six years of follow-up.

Sanfilippo syndrome type B (MPS IIIB) is characterized by progressive cognitive decline, behavioral challenges, and eventual loss of motor function. Most patients do not survive beyond their late teens, and current care is limited to managing symptoms.

TA-ERT is designed to overcome a key limitation of traditional enzyme replacement therapies, which typically cannot reach the brain. The therapy combines a modified version of the missing NAGLU enzyme with a targeting component that helps it enter cells more effectively, allowing delivery to lysosomes in the central nervous system.

The program has received multiple regulatory designations from the U.S. Food and Drug Administration, including Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations.

In a cohort of 22 patients enrolled across multiple studies, treatment led to rapid and sustained normalization of a key disease biomarker—heparan sulfate non-reducing end—in the cerebrospinal fluid. Elevated levels of this substance are believed to drive brain damage in MPS IIIB.

Beyond biomarker improvements, researchers reported stabilization across several areas that typically decline over time in untreated patients. Cognitive performance remained stable compared to natural history data, and communication and motor skills were also preserved.

Brain imaging findings supported these results, showing stabilization of gray matter volume, while untreated patients typically experience progressive brain atrophy. Other disease-related measures, such as liver and spleen enlargement, also improved.

“In a progressive neurodegenerative disease like MPS IIIB, stability itself is a clinically meaningful outcome,” said Nicole Muschol, principal investigator of the TA-ERT program. “Over six years, we observed sustained reductions in heparan sulfate alongside preservation of cognition, communication, and motor function compared to untreated patients.”

The therapy’s safety profile was consistent with previous findings for this type of administration, with approximately 6,000 doses delivered across the study population.

If these results are confirmed in future studies and regulatory review, TA-ERT could represent a meaningful shift in how MPS IIIB is treated—moving beyond supportive care toward a therapy that may slow or halt disease progression.