Page 84 - Demo

Chapter 482of all MPS cases diagnosed and the combined birth prevalence is 1.89 per 100.000 live births.24 It is characterized by progressive intellectual neurologic deterioration (PIND)25 and severe and progressive behavioral and sleeping problems including restless, destructive, chaotic, anxious and sometimes aggressive behavior.26 There is yet no curative treatment.23 To date, no evidence exists for the efficacy of CBD for MPS III, although a potential treatment approach has been described that focuses on modulation of the endocannabinoid system in lysosomal storage disorders including MPS III.27FXS is a relatively more common genetic disorder associated with ID. It is X-linked, occurs in approximately 1:4000 males and 1:8000 females, and is caused by an alteration in the recently renamed Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene containing a CGG-repeat with repeat length exceeding 200 CGGs.28,29 Other manifestations include ADHD (70%), ASD (60%), and anxiety (80%). A recent trial with transdermal CBD gel showed good efficacy on irritability in children with FXS.9 The role of the endocannabinoid system in FXS, its dysregulation due to the absence of Fragile X Messenger Ribonucleoprotein (FMRP), and the potential role of CBD has been previously described.13,30 The endocannabinoid system facilitates synaptic homeostasis and plasticity through the cannabinoid receptor 1 (CB1) on presynaptic terminals, resulting in feedback inhibition of neuronal signaling, which are thought to be disrupted in FXS and may be restored by CBD acting as a negative allosteric modulator of CB1.31 These findings suggest that the endocannabinoid system may be involved in the neurodevelopment and behavior regulation.Rationale for the N-of-1 design Trials in RGNDs pose specific methodological challenges due to comorbidities and rarity of conditions.32,33 Additionally, patients with rare disorders require individualized treatments and outcome measures due to their heterogeneity and vulnerability. It is therefore difficult to conduct traditional randomized controlled trials (RCTs) to determine effectiveness. The N-of-1 methodology is an alternative type of RCT, providing rigorous, and the highest level of evidence of treatment effectiveness at an individual level and is consistent with the movement towards personalized care.34,35N-of-1 studies are randomized, controlled, multiple cross-over trials within Annelieke Muller sHL.indd 82 14-11-2023 09:07