Spironolactone Improved Children With NCOR Mutations
Status:
NOT_YET_RECRUITING
Trial end date:
2025-10-30
Target enrollment:
Participant gender:
Summary
NCOR1/2 constitutes the NCOR complex, which interacts with many different nuclear receptors to produce special physiological effects. These receptors further recruit epigenome modifying enzymes that are involved in the transcription of multiple genes involved in neurotransmission and synaptic plasticity. Studies of mice with gene knockout and autistic patients with NCOR mutations have found that both exhibit clinical symptoms characteristic of ASD, such as deficits in social interaction, spatial learning and impaired recognition memory. Further study revealed that the cause was the hyperexcitability of GABaergic neurons in the lateral hypothalamus (LH) due to the NCOR1/2 defect, which impaired synaptic plasticity in the hippocampal CA3 region through the single synaptic LHGABA-CA3 neural projection, and thus exhibited learning/memory impairment. Therefore, drugs that affect the NCOR receptor can improve learning/memory impairment by affecting GABA neurons. Spironolactone is a widely used diuretic with good safety. It is widely used in the treatment of hypertension, edema and anti-androgen therapy in children. In this study, spironolactone is one of the most popular drugs used to treat children with NCOR gene mutation. In our previous animal experiments, we found that spironolactone could treat NCOR mutant mice and improve ASD-related symptoms, such as reduced sensorimotor capacity, learning disability and impaired working memory; Moreover, the efficacy of related diuretics in the treatment of ASD diseases has been proved clinically. So spironolactone may be a new target for the treatment of NCOR patients in the future.