Clinical Research Directory

Spironolactone Improved Children With Gene Mutations Related to NCOR

MECP2, a key transcriptional regulator, has been shown to interact with the NCOR1/2 complex to modulate gene expression. Specifically, MECP2 recruits the NCOR complex to specific genomic loci, facilitating histone deacetylation and chromatin remodeling, which are essential for the proper regulation of genes involved in synaptic function and neuronal maturation. Disruptions in the MECP2-NCOR interaction have been implicated in neurodevelopmental disorders, including Rett syndrome and autism spectrum disorder (ASD), highlighting the collaborative role of MECP2 and the NCOR1/2 complex in maintaining neuronal homeostasis. Building on this, NCOR1/2 constitutes the NCOR complex,interacts with many different nuclear receptors to produce special physiological effects. The 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 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. Spironolactone is widely used in the treatment of hypertension, edema, and anti-androgen therapy in children. Spironolactone is currently under investigation as a potential treatment for children with NCOR gene mutations. Preclinical studies have demonstrated that spironolactone can ameliorate ASD-related symptoms in NCOR mutant mice, including reduced sensorimotor capacity, learning disability, and impaired working memory. Furthermore, the efficacy of related diuretics in the treatment of ASD has been demonstrated clinically. Therefore, spironolactone may represent a novel therapeutic target for patients with NCOR-related gene mutations in the future.

Regulating Blood Pressure During Recovery From Intracerebral Hemorrhage and Ischemic Stroke

The purpose of this research study is to determine whether blood pressure treatment regimens with spironolactone are better than blood pressure treatment regimens without spironolactone at lowering blood pressure in stroke survivors.