Method for the treatment of Dravet syndrome

• US 10,478,441 B2
• Filed: 02/10/2017
• Issued: 11/19/2019
• Est. Priority Date: 05/03/2013
• Status: Active Grant

• Current Assignee: Katholieke Universiteit Leuven, University Hospital Antwerp
• Original Assignee: Katholieke Universiteit Leuven
• Inventors: Ceulemens, Berten, Lagae, Lieven
• Primary Examiner(s): Kantamneni, Shobha
• Application Number:
  US15/429,516
• Publication Number:
  US 20170151213A1
• Time in Patent Office: 1,012 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/36 Compounds containing methylenedioxyphenyl groups, e.g. sesamin
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers

Abstract

A method of treating and/or preventing Dravet Syndrome in a patient such as a patient previously diagnosed with Dravet Syndrome, by administering an effective dose of fenfluramine or its pharmaceutically acceptable salt to that patient. Dravet Syndrome patients are typically children under the age of 18 and are treated at a preferred dose of less than about 0.5 to about 0.01 mg/kg/day.

Claims

1. A method of stimulating 5-HT receptors in the brain of a patient diagnosed with Dravet syndrome, comprising:

administering to the patient 0.2 mg/kg/day of fenfluramine or a pharmaceutically acceptable salt thereof; and

administering to the patient an effective dose of stiripentol or a pharmaceutically acceptable salt thereof;

whereby 5-HT receptors are stimulated and wherein the 5-HT receptor is in a family of receptors selected from the group consisting of 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7.

2. The method of claim 1, wherein the 5-HT receptor is in the 5-HT1 receptor family and is selected from the group consisting of 5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT1E, 5-HT1F.

3. The method of claim 1, wherein the 5-HT receptor is in the 5-HT2 receptor family and is selected from the group consisting of 5-HT2A, 5-HT2B, 5-HT2C.

4. The method of claim 1, wherein the 5-HT receptor is the 5-HT3 receptor.

5. A method of stimulating 5-HT receptors in the brain of a patient diagnosed with Dravet syndrome, comprising:

administering to the patient an effective dose of fenfluramine or a pharmaceutically acceptable salt thereof administered in a dose of 0.5 mg/kg/day to 0.2 mg/kg/day to the patient; and

administering to the patient an effective dose of stiripentol or a pharmaceutically acceptable salt thereof;

whereby 5-HT receptors are stimulated.

6. The method of claim 5, wherein the effective dose is administered in the form of one or more dosage forms for oral, injectable, transdermal, inhaled, nasal, rectal, vaginal or parenteral delivery.