Anakinra shows promise in reducing symptoms in patients with Sanfilippo syndrome

As a neurodegenerative disease characterized by childhood-onset dementia, Sanfilippo syndrome causes enormous suffering in many ways, including pain, loss of speech, extreme agitation and anxiety, gastrointestinal symptoms, and profound sleep disturbances. In the absence of an approved treatment, clinical specialists have not yet had the ability to alleviate this suffering. Groundbreaking clinical research collaboration between principal investigator and principal investigator Lynda Polgreen, MD, MS, an 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 Scientific Director and co-author of the study, MD. Cara O’Neill, M.D., FAAP, has taken an novel approach to treating this disease, targeting neuroinflammation, which is believed to be a key cause of the disease’s symptoms.

Dr. Polgreen’s team used anakinra, a recombinant interleukin-1 receptor antagonist, in children and newborn adults with moderate to advanced stages of the disease, which means all of them had debilitating and life-limiting symptoms when they entered the study. Although clinical trials are ongoing to find a cure for Sanfilippo syndrome, such trials are restricted to specific subtypes of the disease and only include the youngest children who show very few symptoms because the disease is considered irreversible. As a result, over 99% of the Sanfilippo population was deprived of the opportunity to receive targeted treatment. However, the research team’s revolutionary clinical trial aimed to improve representation of this long-excluded part of the Sanfilippo community by treating people who are already significantly impacted by the disease.

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is considered an orphan disease, classifying it with particular emphasis on drug development and policy. It is a scarce genetic disease in which the body is unable to break down the complicated molecule heparan sulfate. The accumulation of heparan sulfate in cells then causes several biological consequences, including inflammation, ultimately leading to progressive dementia and systemic diseases. Anakinra works by inhibiting interleukin-1 (IL-1), a key mediator of the inflammatory response. By blocking IL-1 activity, anakinra reduces harmful inflammation in the body and brain. This study provides evidence for the first time that anakinra can positively impact significant disease symptoms in patients with Sanfilippo syndrome.

In a phase 1/2 study, investigators evaluated the safety, tolerability, and effects of anakinra on neurobehavioral, functional, and quality of life outcomes in patients with several subtypes of Sanfilippo syndrome. The results showed that anakinra is sheltered and associated with significant improvement in many symptom areas. By week 36 of treatment, 94% of participants showed improvement in at least one area. Most side effects were gentle, with injection site reactions being the most common. Most importantly, no solemn adverse events have been reported with anakinra, highlighting its safety profile.

Dr. Lynda Polgreen, principal investigator of the study, expressed optimism about the results: “The changes we have seen in our patients represent a significant improvement in the everyday lives of people with Sanfilippo syndrome and their families. “This study highlights the potential of anakinra as an adjunctive treatment option and highlights the broader importance of targeting downstream effects, such as inflammation, in lysosomal diseases.”

“Together with Dr. Polgreen, we saw an opportunity to translate existing pre-clinical proof-of-concept research into a drug repurposing trial that could provide immediate benefits to children. The Cure Sanfilippo Foundation is proud to have collaborated 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 urgent needs of the patient community. We are also grateful for the collaboration with Sobi, who generously provided the study drug. This close collaboration and integration of the patient/caregiver perspective facilitated the employ of novel endpoint instruments and a patient-centered trial design that will underpin future drug development for this extremely scarce disease,” Dr. O’Neill said.

“The funding provided by the Cure Sanfilippo Foundation to support all clinical research and patient journey activities was made possible by generous donors and families who support the Foundation’s mission to create up-to-date life-changing opportunities. We look forward to working with the Lundquist Institute to advance additional clinical trials programs,” said Glenn O’Neill, president and co-founder of the Cure Sanfilippo Foundation.

This research has made immediate progress towards meeting the need for facilitate for all people affected by this disease, regardless of their disability. This study promises to improve the life experiences not only of people diagnosed with Sanfilippo syndrome, but also their families who deal with the myriad stresses and heartaches associated with the disease.”

Dr. Julie Eisengart, associate professor of pediatrics and director of the Scarce Disease Neurodevelopmental Program at the University of Minnesota Medical School

This study supports the potential of anakinra as a therapeutic option for the treatment of Sanfilippo syndrome. It opens the door to its employ in other MPS and similar neurodegenerative disorders characterized by neuroinflammation. Given these encouraging results, further research is needed to discover anakinra’s full potential to alter the course of Sanfilippo syndrome and provide hope to affected families around the world.