SOUTH SAN FRANCISCO, Calif., June 8, 2026
Spruce Biosciences announced new long-term clinical data demonstrating the potential of tralesinidase alfa enzyme replacement therapy (TA-ERT) as a disease-modifying treatment for Sanfilippo Syndrome Type B (MPS IIIB), a rare and fatal neurodegenerative lysosomal storage disorder with no approved therapies. Presented at the 18th International MPS & Related Lysosomal Diseases Symposium in Florence, Italy, the findings showed that treatment with TA-ERT resulted in rapid and sustained normalization of disease-related biomarkers while preserving cognitive and functional abilities over a six-year period compared with untreated natural history patients. The data further strengthen the clinical evidence supporting TA-ERT as a potential breakthrough therapy for addressing the underlying neurological progression of MPS IIIB.
Long-Term Treatment Delivers Durable Biomarker Improvements
The analysis included 22 patients who participated in interventional and extension studies of TA-ERT and were followed for up to six years. Researchers reported that treatment rapidly reduced and durably normalized cerebrospinal fluid heparan sulfate non-reducing end (CSF HS-NRE) levels, a biomarker considered reasonably likely to predict clinical benefit in patients with MPS IIIB. Excess accumulation of heparan sulfate in the brain is a key driver of disease progression, leading to widespread neuronal damage and progressive neurological decline. The sustained reduction of this biomarker throughout the study period suggests that TA-ERT is effectively targeting the underlying cause of the disease rather than simply managing symptoms. Investigators noted that the durability of biomarker normalization provides important support for the therapy’s potential disease-modifying effects.
Cognitive, Communication and Motor Skills Remain Stable
Beyond biomarker improvements, the study demonstrated meaningful long-term preservation of neurological and functional outcomes. Patients receiving TA-ERT maintained cognitive performance, communication abilities, and motor function relative to untreated natural history cohorts, which typically experience progressive deterioration. Assessments using the Bayley Scales of Infant and Toddler Development and the Vineland Adaptive Behavior Scales showed stabilization of cognitive development, receptive and expressive language skills, and both fine and gross motor function over time. Researchers also observed stabilization of cortical gray matter volume, an important indicator of brain integrity that normally declines as neurodegeneration advances. These findings are particularly significant because MPS IIIB is characterized by relentless neurological decline that eventually results in severe disability, loss of independence, and premature death.
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Potential First Disease-Modifying Therapy for MPS IIIB
Sanfilippo Syndrome Type B is an ultra-rare inherited disorder caused by deficiency of the N-acetyl-alpha-glucosaminidase (NAGLU) enzyme, which is required for the breakdown of heparan sulfate in lysosomes. The resulting accumulation of toxic substrates progressively damages the central nervous system and leads to cognitive impairment, behavioral abnormalities, communication deficits, motor dysfunction, and shortened life expectancy. Currently, there are no FDA-approved therapies available for patients with MPS IIIB, and treatment is limited to supportive and palliative care. According to investigators, the ability of TA-ERT to preserve neurological and adaptive function over six years highlights its potential to become the first disease-modifying treatment for this devastating condition. Maintaining stability in a progressive neurodegenerative disease is widely considered a clinically meaningful outcome for both patients and caregivers.
Safety Profile Supports Continued Clinical Development
The long-term data also demonstrated a safety profile generally consistent with intracerebroventricular administration of enzyme replacement therapy. Over the course of the clinical development program, approximately 6,000 doses of TA-ERT were administered to 22 patients. No new safety concerns were identified during the six-year follow-up period, supporting the feasibility of chronic treatment. TA-ERT is specifically designed to restore NAGLU enzyme activity within the central nervous system through direct intracerebroventricular delivery, allowing the therapy to reach affected brain tissues and promote clearance of accumulated heparan sulfate. With multiple FDA designations including Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug status, TA-ERT continues to advance as one of the most promising investigational therapies for rare pediatric neurodegenerative disorders. The latest findings reinforce its potential to alter the course of MPS IIIB and address a significant unmet medical need for affected children and families.
Source: Spruce Biosciences press release
