Landmark ‘Nature Medicine’ Study Reports Promising New Treatment Reduces Suffering in Sanfilippo syndrome

June 21, 2024

In an open label study, the blood-brain barrier crossing anti-inflammatory anakinra was found to be safe and associated with improved neurobehavioral and functional outcomes in Sanfilippo syndrome.


LOS ANGELES, CA, & COLUMBIA, SC (June 21, 2024) — As a neurodegenerative disease characterized by childhood onset dementia, Sanfilippo syndrome causes immense suffering in many ways, including pain, loss of speech, extreme agitation, and distress, gastrointestinal symptoms, and profound sleep disturbance. With no approved treatment, clinical specialists have had few options to help alleviate this suffering until now. A groundbreaking clinical trial collaboration between study lead and principal investigator Lynda Polgreen, MD, MS, Investigator at The Lundquist Institute for Biomedical Innovation at Harbor-UCLA (TLI) and Associate Professor of Pediatrics at the David Geffen School of Medicine at UCLA and Cure Sanfilippo Foundation’s Chief Science Officer and study co-investigator Cara O’Neill, MD, FAAP, used an innovative approach to treat this disease by targeting neuroinflammation, as it is thought to be a key contributor to disease symptoms.

Dr. Polgreen’s team used anakinra, a recombinant interleukin-1 receptor antagonist, in children and young adults with moderate to advanced stages of the condition, meaning they were all experiencing debilitating, life-limiting symptoms at the time of study enrollment. While ongoing clinical trials are searching for a cure for Sanfilippo syndrome, such trials are restricted to specific disease subtypes and include only the youngest of children exhibiting very few symptoms because the disease is considered irreversible. This has left more than 99% of the Sanfilippo population without any opportunity to receive focused treatment. However, the research team’s revolutionary clinical study was designed to improve the representation of this long-excluded segment of the Sanfilippo community by treating individuals who have already been significantly impacted by their disease.

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is considered an orphan disease, which classifies it for special considerations in drug development and policy. It is a rare genetic disorder in which the body is unable to break down the complex molecule heparan sulfate. Accumulation of heparan sulfate in cells then triggers several biological consequences, including inflammation, ultimately leading to progressive dementia and body-wide disease. Anakinra works by inhibiting interleukin-1 (IL-1), a key mediator of the inflammatory response. By blocking the activity of IL-1, anakinra reduces harmful inflammation in the body and brain. For the first time, this study provides evidence that anakinra can positively impact meaningful disease symptoms in patients with Sanfilippo syndrome.

In the phase 1/2 trial, researchers evaluated anakinra’s safety, tolerability, and effects on neurobehavioral, functional, and quality-of-life outcomes in patients with several subtypes of Sanfilippo syndrome. Results showed anakinra was safe and associated with significant improvements in multiple symptom domains. By week 36 of treatment, 94% of participants showed improvement in at least one domain. Most adverse events were mild, with injection site reactions being the most common. Crucially, no serious adverse events related to the use of anakinra were reported, underscoring its safety profile.

Dr. Lynda Polgreen, the study’s principal investigator, expressed optimism about the results, “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.”

“Together with Dr. Polgreen, we recognized an opportunity to translate existing preclinical proof of concept research into a drug repurposing trial which had the potential to benefit children imminently. Cure Sanfilippo Foundation is proud to have partnered with and supported this highly skilled and compassionate research team led by Dr. Polgreen (TLI), including the expertise of Dr. Eisengart (University of Minnesota) and Dr. Chen (TLI), to address the urgent needs of the patient community. We are also grateful to have collaborated with Sobi, who generously provided study drug. This close collaboration and integration of patient/caregiver perspectives have facilitated using novel outcome instruments and patient-centered study design that will inform future drug development in this ultra-rare disease,” reflected Dr. O’Neill.

“Funding provided by Cure Sanfilippo Foundation to support all clinical trial activities and patient travel was made possible by generous donors and families who support the Foundation’s mission; creating new opportunities to transform lives. We look forward to partnering with The Lundquist Institute to advance additional clinical programs,” said Cure Sanfilippo Foundation President and Co-Founder Glenn O’Neill.

“This study has made immediate strides toward addressing the need to help all people touched by this condition, regardless of their level of disability,” noted Julie Eisengart, Ph.D., Associate Professor of Pediatrics and Director of the Neurodevelopmental Program in Rare Disease at the University of Minnesota Medical School. “This trial shows promise for improving the lived experience of not only the people diagnosed with Sanfilippo syndrome, but also their families who face countless disease-related stressors and heartache.”

This study supports the potential of anakinra as a therapeutic option for Sanfilippo syndrome. It 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.

Article title: “Anakinra for Sanfilippo syndrome: a phase 1/2 trial” (NMED-A129940C)

The article DOI: 10.1038/s41591-024-03079-3

About Cure Sanfilippo Foundation

Cure Sanfilippo Foundation is a 501(c)(3) nonprofit organization that drives research funding, collaboration, and advocacy with a mission to accelerate the development of treatments that lead to functional cures and improve the lives of children with Sanfilippo syndrome. Established in 2013 by parents inspired to action by their own child’s diagnosis, Cure Sanfilippo has, to date, funded over 50 research grants worldwide, leading to three clinical treatment trials for individuals with Sanfilippo syndrome. In addition to funding research, the Foundation works collaboratively with the FDA, the patient community, pharmaceutical industry, and numerous other stakeholders to ensure that clinical trial programs and regulatory decisions integrate the real world lived experience of individuals with Sanfilippo syndrome. This has led the foundation to have a special focus on trial endpoints informed by Foundation led patient preference research, trial operations, and broad outreach to support earlier diagnosis. Providing individualized support for families and their care team navigating new diagnoses, exploring clinical trial participation, and the myriad of challenges and joys throughout their lives is a special honor for Foundation staff. Learn more about Sanfilippo syndrome and the Foundation at

About The Lundquist Institute

The Lundquist Institute is an innovation engine with a global reach and a reputation of more than 70 years of improving and saving lives. With its new medical research building, its state-of-the-art incubator, “BioLabs LA at The Lundquist,” existing laboratory and support infrastructure, and the development of a new 15-acre business BioCenter tech park, The Lundquist Institute serves as a hub for the Los Angeles area’s burgeoning biotech scene. Alongside its research and commercialization work, TLI has developed a robust community outreach effort that includes a science education pipeline that extends from the elementary grade level to the PhD as well as community health programs that are a direct benefit to 60,000 women, children, and families each year who are at risk of preventable disease or medical neglect.

About the University of Minnesota Medical School

The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit

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