Study of Cannabidiol in Sanfilippo Syndrome

Sanfilippo syndrome, or Mucopolysaccharidosis type III (MPS III), is a rare genetic lysosomal storage disease characterized by the accumulation of heparan sulfate due to insufficient production of lysosomal enzymes. Consequently, a buildup of heparan sulfate causes progressive neurodegeneration, leading to significant neurobehavioral problems. These neurobehavioral symptoms are highly disruptive and distressing to families, have a significant impact on the quality of life of the patients and their families, and likely interfere with adjunctive therapeutic attempts at supporting the child. To date, there are no approved therapies for the treatment of the neurobehavioral symptoms of Sanfilippo syndrome. Cannabidiol (CBD), a compound derived from the cannabis plant but without the psychoactive effects, has been shown to be safe and effective in the treatment of children with severe epilepsy disorders. Studies have shown that CBD improves behavior in children with autism. This study will use Epidiolex, a pharmaceutical-grade purified oral solution of cannabidiol that was approved by the FDA for the treatment of severe pediatric epilepsy disorders. Study subjects will include approximately 35 participants with Sanfilippo syndrome. Participants will undergo baseline clinical evaluations, and neurobehavioral, and functional outcomes will be collected from parent-reported questionnaires. Participants will then receive either Epidiolex or placebo for 16 weeks. Following this period and an 8-week washout, participants will cross over and receive the opposite treatment for 16 weeks. Safety labs and questionnaires will be collected throughout these periods to assess safety and efficacy. Participants and study personnel will be blinded to the treatment status of each participant. When this blinded portion of the trial is completed, all participants will receive Epidiolex open-label for 52 weeks to measure long-term safety. The type and severity of adverse events will be collected to measure safety, and different behavioral and functional outcomes will be collected to measure efficacy.