Table 2.
Summary of new drugs under clinical trials in fragile X syndrome [95].
| Medication | Drug Class | Mechanism of Action |
Target Problems | Dose/Day | Common Side Effects |
|---|---|---|---|---|---|
| Cannabidiol (CBD) | Phytocannabinoid exhibits no effects indicative of any abuse or dependence potential |
Multiple: Interact with an FXS-compromised endocannabinoid system; positively affect synaptic plasticity; a positive allosteric modulator of GABAA receptors; Serotonin 1A receptors modulator | Multiple: Reductions in social avoidance and anxiety; improvements in sleep, feeding, motor coordination, language skills, anxiety, seizures and sensory processing | Oral tincture: 25 to 50 mg per dose up to bid Topical ointments: 125 mg to 500 mg bid |
Sedation, but rare cases of activation. Higher doses may cause liver function test elevations. Topicals may cause skin rash or irritation |
| BPN14770 | Phosphodiesterase-4D (PDE4D) inhibitor | Selectively binding to and partially suppressing the activity of phosphodiesterase 4D (PDE4D), an enzyme known to regulate a brain cyclic adenosine monophosphate (cAMP). | Cognitive function, language and daily functioning | Adult: 25 mg bid | The most commonly reported side effects were vomiting and upper respiratory infections |
| Metformin | Oral antidiabetic; Class: biguanides | Impacts mTOR and ERK/MAPK pathways through the AMP- activated protein kinase pathway. Decreases the level of protein MMP-9 in FXS |
Intellectual abilities, behavioral problems, speech and language deficits, weight management | 500 mg bid < 50 kg 1000 mg bid > 50 kg |
Gastrointestinal side effects (nausea, diarrhea and abdominal discomfort), headache, weight loss, dizziness, inadequate vitamin B12 |
| Minocycline | Antibiotic; Class: tetracycline |
Anti-inflammatory, MMP inhibition and anti-apoptotic effects. Inhibition of activity of the protein MMP-9 in FXS |
Overall clinical improvement; In particular, mood and anxiety-related behaviors | 25 mg < 25 kg 50 mg 25–45 kg 100 mg > 45 mg |
Gastrointestinal side effects (nausea, diarrhea, etc.), dizziness, discoloration of skin, nails or gums |