NLX-101 : a novel treatment for Rett syndrome (RTT), an orphan disorder
NLX-101 (previously known as F15599) is a novel compound that activates serotonin 5-HT1A receptors  with exceptional selectivity, having over 1000-fold higher affinity for this target over other receptors. In addition, NLX-101 is a 'biased agonist' at 5-HT1A receptors, preferentially activating 5-HT1A receptors in those brain regions that control mood and cognition. In animal models, NLX-101 is very active in a rat test of antidepressant activity following a single administration, whereas currently used antidepressants require repeated administration to show activity. NLX-101 also robustly restores memory deficits. These pronounced antidepressant and cognitive enhancing properties are not seen with older 5-HT1A agonists.
Treatment of breathing deficits in Rett syndrome using NLX-101
A dysfunction of the serotonergic system has been described for Rett syndrome (RTT), with supporting data coming from Rett patients and from transgenic mouse models . Taken together, these data suggest that a selective 5-HT1A receptor agonist would be of therapeutic benefit for Rett syndrome patients.
The effects of NLX-101 were investigated in a transgenic mouse model of Rett syndrome. These mice exhibit severe breathing difficulties, including apneas and respiratory irregularity, similar to those seen in girls with Rett syndrome. Notably, the administration of NLX-101 in Rett mice robustly reduced the occurrence of apneas and normalized the irregular breathing patterns  without interfering with other behaviors. These data suggest that NLX-101 may represent a promising strategy for treating breathing disturbances in Rett syndrome: a cardiorespiratory study of NLX-101 in Rett mice is being supported by a grant from the International Rett Syndrome Foundation. Rett syndrome patients also exhibit high levels of mood deficits and are cognitively impaired: NLX-101 treatment may bring additional benefit in these areas.