Methods for treating dravet syndrome

A syndrome and subject technology, applied in drug combinations, pharmaceutical formulations, active ingredients of heterocyclic compounds, etc., can solve problems such as insufficient current treatment

Inactive Publication Date: 2020-02-14
CAVION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, current treatments for D

Method used

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  • Methods for treating dravet syndrome
  • Methods for treating dravet syndrome
  • Methods for treating dravet syndrome

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0178] Example 1 Effect of CACNA1G Knockout on Dravet Phenotype

[0179] The Dravet mouse model (see, e.g., Miller et al., Genes Brain Behav. 2014, 13:163-72) was bred to Cav3.1 genetic knockout (KO) mice to generate hybrids of Cacna1g in the Dravet mouse model. KO( figure 1 ). Dravet mice and Cav3.1 KO were tested for spontaneous tonic-clonic seizures and survival. Such as Figure 2A and 2B As shown, in Scn1a + / - Heterozygous deletion of Cacna1g confers a protective benefit on spontaneous generalized tonic-clonic seizures and survival in the Dravet model These data suggest that Cav3.1 may be a useful therapeutic target in the treatment of Dravet syndrome.

Embodiment 2

[0180] Example 2 TTA-A2 to Scn1a + / - Impact of the mouse model

[0181] will be at Scnla + / - TTA-A2, a selective Cav3 antagonist, was evaluated in a mouse model of hyperthermia-induced seizure screening (see eg Miller et al., Genes Brain Behav. 2014, 13: 163-72). Mice will be randomly assigned as treatment or control groups and will be administered TTA-A2 or vehicle by oral gavage. Hyperthermia will be induced until a seizure occurs or maximal temperature is reached, for example, as in image 3 shown. The number of generalized tonic-clonic (GTC) mice was compared between the control and treatment groups. Such as image 3 As shown, "-X" minutes will be determined based on TTA-A2 pharmacokinetics such that maximum brain exposure occurs during seizure induction. The pharmacokinetic data of TTA-A2 are shown in Table 2-3 below. The animal's body temperature will be raised up to 42.5°C and maintained for three minutes or until GTC seizures are observed.

[0182] Table 2

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Abstract

Provided herein are methods of treating Dravet syndrome that include administering an effective amount of a T-type calcium channel antagonist to a subject in need of the treatment.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of US Patent Application Serial No: 62 / 490,357 filed April 26, 2017. The disclosure of this prior application is considered part of (and is incorporated by reference into) the disclosure of the present application. technical field [0003] The present disclosure relates to the treatment of diseases by administering pharmaceutical compounds. In particular, the present disclosure relates to the treatment of Dravet syndrome by administration of T-type calcium channel antagonists. Background technique [0004] T-type calcium channels are low voltage activated calcium channels that open during membrane depolarization and mediate calcium influx into cells following an action potential or depolarizing signal. T-type calcium channels are known to exist in cardiac and smooth muscle, and also in many neuronal cells within the central nervous system. T-type calcium channels (transiently open...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K38/09A61K31/433A61P25/08A61P25/00A61P25/20A61P25/28
CPCA61K38/00A61K45/06A61K31/44A61P25/00A61P25/08A61P25/20A61P25/28A61K31/4412A61K31/00A61K33/24
Inventor 由李·马里切尔埃文·纽博尔德
Owner CAVION INC
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