Diuretic drug Bumetanide discovered to alleviate symptoms of Angelman syndrome in mice experiments.
A groundbreaking study led by Dr. Ryuichi Shigemoto in Japan has revealed promising results for a potential therapeutic strategy in treating patients with Angelman syndrome. The research, published in the journal Scientific Reports, focused on the effects of the diuretic medication bumetanide on cognition and seizure latency in a mouse model of the condition.
Angelman syndrome is a neurogenetic disorder that occurs when a gene called UBE3A is missing or doesn't work properly. As a result, the brain doesn't develop as it should, causing problems with cognitive function and seizures. To understand how certain proteins behave in Angelman syndrome, the researchers compared mice lacking a properly working Ube3a gene with their healthy littermates.
The research team focused on NKCC1 and KCC2, proteins that transport electrolytes into and out of cells. In mature neurons, KCC2 is most abundant and helps transport chloride out of cells, while NKCC1 is most abundant in nerve cells until right after birth and helps transport chloride into cells.
The study found that in Angelman syndrome, the level of KCC2 in the hippocampus brain region was 18% lower compared to wild-type mice, while the level of NKCC1 was 14% higher. These imbalances may contribute to the symptoms of Angelman syndrome.
To test the effects of bumetanide, the diuretic was administered for 21-28 days using an osmotic pump for controlled delivery. The medication worked by blocking NKCC1, a protein that regulates the flow of chloride and other electrolytes.
The researchers found that bumetanide helped the Angelman syndrome mouse model identify a novel object in a novel object recognition test, indicating improved cognitive function. Additionally, chronic administration of bumetanide effectively improved cognitive dysfunction in the mouse model.
The study also found that bumetanide lengthened the time to a flurothyl-triggered seizure, suggesting that it may be a potential therapeutic strategy for improving seizure latency in patients with Angelman syndrome. However, the medication did not help improve the motor coordination of the mice in a rotarod test.
The findings of this study suggest that blocking NKCC1 activity may be a potential therapeutic strategy for improving cognitive dysfunction and epilepsy in Angelman syndrome. If these findings can translate into humans, the blockage of NKCC1 may be a potential therapeutic strategy for patients with Angelman syndrome. Further research is needed to confirm these results and to explore the safety and efficacy of bumetanide as a treatment for Angelman syndrome.
