Table 4.

Recent clinical trials for treatments targeting specific molecular mechanisms of fragile X syndrome

Compound	Target and effect	Study, patients	Treatment outcomes	References
Acamprosate	mGluR5	Open-label trial with three male patients with FraX.	Improved linguistic communication and global clinical benefit.	[114]
AFQ056	mGluR5	Randomized, double-blind, two-treatment, two-period, crossover study of 30 male patients with FraX.	Did not improve primary outcome measure, ABC-C score. However, patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved. No response was found in patients with partial promoter methylation.	[115▪▪]
Memantine	NMDA antagonist	Open-label trial with six patients with FraX.	Symptom-specific rating scales showed no statistically significant improvement. However, four of six patients showed global clinical benefit on ratings with the CGI-I.	[116]
Donepezil	Enhanced cholinergic neurotransmission	Open-label trial 12 adolescent and young adult patients with FraX for 6 weeks.	Increased CNT scores and decreased ABC Total, Hyperactivity, and Irritability scores as well as decreased CBCL/ABCL Attention Problems scores.	[117]
Riluzole	Agonist of GABAA receptors, synaptic and extrasynaptic; inhibitor of GABA transporters (GAT)	Six-week open-label prospective pilot study of riluzolein with six adults with FraX.	No significant clinical response was detected.	[118]
Valproic acid	Histone deacetylase inhibitor	Open-label study with 10 boys with FraX and ADHD.	Reduced ADHD symptoms as measured by CPRS.	[119]

ABC, Aberrant Behavior Checklist; ABCL, Adult Behavior Checklist; CBCL, Child Behavior Checklist; CGI-I, Clinical Global Impression – Improvement; CNT, Contingency Naming Task; CPRS, Conner′s Parent Rating Scale – Revised.