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We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1\/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6\u201326\u2009years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. 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A.H.C. has a research grant\/contract with Takeda. J.A. and G.B. have research grants\/contracts from the Cure Sanfilippo Foundation. C.O. is an employee of the Cure Sanfilippo Foundation, a non-profit organization; has served as a consultant for Denali Therapeutics, JCR Pharmaceuticals and Lysogene; and participated on a data safety monitoring board or advisory board for BioMarin, Lysogene and Ultragenyx. J.B.E. has research grants\/contracts with Orchard Therapeutics, Prevail and Lysogene; received consulting fees from Denali Therapeutics, JCR Pharmaceuticals, Novel Pharma, Orchard Therapeutics, Regenxbio, Sanofi Genzyme, Sumitomo Pharma Co., Ltd. and Takeda; and received honoraria from Takeda. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}