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A recent clinical trial has shown that anakinra, a recombinant interleukin-1 receptor antagonist, may significantly reduce symptoms in patients suffering from Sanfilippo syndrome, a rare and devastating neurodegenerative disease. This discovery offers a glimmer of hope for families affected by this condition, which is characterized by childhood onset dementia, pain, loss of speech, extreme agitation, distress, gastrointestinal symptoms, and profound sleep disturbances.
A Collaborative Effort for Innovative Treatment
The clinical trial was led by Dr. Lynda Polgreen, MD, MS, an investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA and an Associate Professor of Pediatrics at the David Geffen School of Medicine at UCLA. Dr. Polgreen collaborated with Dr. Cara O’Neill, MD, FAAP, Chief Science Officer at the Cure Sanfilippo Foundation. Their innovative approach focused on targeting neuroinflammation, believed to be a key contributor to the disease’s symptoms.
Dr. Polgreen’s team administered anakinra to children and young adults with moderate to advanced stages of Sanfilippo syndrome, all of whom were experiencing debilitating symptoms. Unlike other ongoing clinical trials, which are often limited to specific disease subtypes and early-stage patients, this study aimed to improve the representation of patients who have already been significantly impacted by the disease.
Understanding Sanfilippo Syndrome
Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is an orphan disease. It is a rare genetic disorder that impairs the body’s ability to break down heparan sulfate, leading to its accumulation in cells. This buildup triggers inflammation and results in progressive dementia and systemic disease. Anakinra works by inhibiting interleukin-1 (IL-1), a key mediator of inflammation, thereby reducing harmful inflammation in the body and brain.
Promising Results from the Clinical Trial
The phase 1/2 trial evaluated anakinra’s safety, tolerability, and effects on neurobehavioral, functional, and quality-of-life outcomes in patients with various subtypes of Sanfilippo syndrome. The results were promising: by week 36 of treatment, 94% of participants showed improvement in at least one symptom domain. Most adverse events were mild, with injection site reactions being the most common, and no serious adverse events related to anakinra were reported.
Dr. Polgreen expressed optimism about the results, stating, “The changes we observed in our patients represent significant improvements in the day-to-day lives of individuals with Sanfilippo syndrome and their families. This trial highlights the potential of anakinra as an adjunctive treatment option and underscores the broader importance of targeting downstream effects, such as inflammation, in lysosomal diseases.”
Collaboration and Future Implications
Dr. O’Neill emphasized the collaborative effort behind the study, reflecting on the partnership with Dr. Polgreen and other experts, including Dr. Eisengart from the University of Minnesota and Dr. Chen from The Lundquist Institute. The trial was supported by generous donations and the support of Sobi, who provided the study drug.
“Cure Sanfilippo Foundation is proud to have partnered with and supported this highly skilled and compassionate research team,” said Dr. O’Neill. “This close collaboration and integration of patient and caregiver perspectives have facilitated using novel outcome instruments and patient-centered study design that will inform future drug development in this ultra-rare disease.”
Glenn O’Neill, President and Co-Founder of the Cure Sanfilippo Foundation, expressed gratitude for the donors and families who made the trial possible. “We look forward to partnering with The Lundquist Institute to advance additional clinical programs,” he said.
Looking Ahead
This study supports the potential of anakinra as a therapeutic option for Sanfilippo syndrome and opens the door to its application in other MPS and similar neurodegenerative disorders characterized by neuroinflammation. With these encouraging results, further research is vital to explore the full potential of anakinra in changing the trajectory of Sanfilippo syndrome and providing hope to affected families worldwide.
Source: The Lundquist Institute
Journal reference: Polgreen, L. E., et al. (2024). Anakinra in Sanfilippo syndrome: a phase 1/2 trial. Nature Medicine, 1–7. doi.org/10.1038/s41591-024-03079-3.
