Delving into the Latest Updates on LifeSplice Pharma LLC with Synapse

概览

疾病领域	数量

神经系统疾病	3
内分泌与代谢疾病	1

排名前五的药物类型	数量

反义寡核苷酸	3

排名前五的靶点	数量

Nav1.6(VIII型钠通道蛋白α亚基)	1

关联

3

项与 LifeSplice Pharma LLC 相关的药物

LSP-GR1

靶点-

作用机制

RNA剪接调节剂

在研机构

LifeSplice Pharma LLC

原研机构

LifeSplice Pharma LLC

在研适应症

肌萎缩侧索硬化 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

LSP-SCN8

靶点-

作用机制

RNA剪接调节剂

在研机构

LifeSplice Pharma LLC

原研机构

LifeSplice Pharma LLC

在研适应症

Dravet综合征

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

LSP-SCN8A

靶点

Nav1.6

作用机制

Nav1.6阻滞剂

在研机构

LifeSplice Pharma LLC

原研机构

LifeSplice Pharma LLC

在研适应症

CDKL5缺乏症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 LifeSplice Pharma LLC 相关的临床结果

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0 项与 LifeSplice Pharma LLC 相关的专利（医药）

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1

项与 LifeSplice Pharma LLC 相关的文献（医药）

PLOS ONE3区 · 综合性期刊

AMPA GluA1-flip targeted oligonucleotide therapy reduces neonatal seizures and hyperexcitability

3区 · 综合性期刊

ArticleOA

作者: Coughlin, David J ; Lykens, Nicole M ; Tallent, Melanie K ; Lutz, Gordon J ; Reddi, Jyoti M

Glutamate-activated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-Rs) mediate the majority of excitatory neurotransmission in brain and thus are major drug targets for diseases associated with hyperexcitability or neurotoxicity. Due to the critical nature of AMPA-Rs in normal brain function, typical AMPA-R antagonists have deleterious effects on cognition and motor function, highlighting the need for more precise modulators. A dramatic increase in the flip isoform of alternatively spliced AMPA-R GluA1 subunits occurs post-seizure in humans and animal models. GluA1-flip produces higher gain AMPA channels than GluA1-flop, increasing network excitability and seizure susceptibility. Splice modulating oligonucleotides (SMOs) bind to pre-mRNA to influence alternative splicing, a strategy that can be exploited to develop more selective drugs across therapeutic areas. We developed a novel SMO, GR1, which potently and specifically decreased GluA1-flip expression throughout the brain of neonatal mice lasting at least 60 days after single intracerebroventricular injection. GR1 treatment reduced AMPA-R mediated excitatory postsynaptic currents at hippocampal CA1 synapses, without affecting long-term potentiation or long-term depression, cellular models of memory, or impairing GluA1-dependent cognition or motor function in mice. Importantly, GR1 demonstrated anti-seizure properties and reduced post-seizure hyperexcitability in neonatal mice, highlighting its drug candidate potential for treating epilepsies and other neurological diseases involving network hyperexcitability.

100 项与 LifeSplice Pharma LLC 相关的药物交易

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100 项与 LifeSplice Pharma LLC 相关的转化医学

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