IP Library › Granted Patent US 12,551,479
Granted Patent B2
US 12,551,479 · App. 17/432,419 · Granted Feb 17, 2026

Acyl-protein thioesterase inhibitor for the treatment and/or prevention of Huntington's disease

Inventors: Frederic Saudou (Grenoble, FR); Amandine Virlogeux (Craponne, FR)
Assignees: UNIVERSITÉ GRENOBLE ALPES; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE; CENTRE HOSPITALIER RÉGIONAL DE GRENOBLE; UNIVERSITÉ PARIS-SACLAY
A61K31/496A61P25/28
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Quick Facts
Patent No.
US 12,551,479
App. No.
17/432,419
Granted
Feb 17, 2026
Kind
B2
Abstract

Disclosed is an inhibitor of the acyl-protein thioesterase APT1, ML-348, of formula A: for use in the treatment and/or prevention of a disease or disorder in a subject in need thereof. In particular the inhibitor is for use in the treatment and/or prevention of a neurodegenerative disease or disorder, particularly Huntington's disease. Also disclosed is a pharmaceutical composition including at least the APT1 inhibitor and at least one pharmaceutically acceptable excipient. The inhibitor or composition is intended for use as a medicament. Furthermore, the inhibitor or composition is intended for use in the treatment and/or prevention of a disease or disorder related to impaired intracellular trafficking between the endoplasmic reticulum and the Golgi apparatus and between the latter and the plasma membrane.

Claims (7)

1 . A method for treating a neurodegenerative disease or disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of ML-348, wherein the therapeutic effect for the neurodegenerative disease or disorder is achieved by selective inhibition of Acyl-Protein Thioesterase 1 (APT1) activity without substantial concomitant inhibition of over Acyl-Protein Thioesterase 2 (APT2) activity, thereby restoring endoplasmic reticulum to Golgi apparatus trafficking in neuronal cells affected by the neurodegenerative disease or disorder.

2 . A method for improving motor coordination in a subject having a neurodegenerative disease or disorder the method comprising chronically administering to the subject ML-348, at a dosage of about 0.3 mg/kg/day for a period of at least 28 days, wherein said ML-348 selectively inhibits Acyl-Protein Thioesterase 1 (APT1), over Acyl-Protein Thioesterase 2 (APT2) activity.

3 . The method of claim 2 , wherein the chronic administration is via subcutaneous infusion using an osmotic pump.

4 . The method of claim 1 , wherein the neurodegenerative disease or disorder is Huntington's disease.

5 . The method of claim 2 , wherein the neurodegenerative disease or disorder is Huntington's disease.

6 . The method of claim 1 wherein the neurodegenerative disease or disorder is any one of Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis or Charcot's disease (ALS), Rett's syndrome, Charcot-Marie-Tooth disease, motor-sensory axonal neuropathy, Perry's syndrome, early-onset autosomal dominant Alzheimer's disease (AD3), progressive supranuclear palsy syndrome (PSP), autosomal spastic paraplegia.

7 . The method of claim 2 wherein the neurodegenerative disease or disorder is any one of Huntington's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis or Charcot's disease (ALS), Rett's syndrome, Charcot-Marie-Tooth disease, motor-sensory axonal neuropathy, Perry's syndrome, early-onset autosomal dominant Alzheimer's disease (AD3), progressive supranuclear palsy syndrome (PSP), autosomal spastic paraplegia.

Assignments (3)
CHANGE OF NAME Recorded Aug 1, 2022
From: CENTRE HOSPITALIER UNIVERSITAIRE GRENOBLE ALPES
To: CENTRE HOSPITALIER RÉGIONAL DE GRENOBLE
Reel/Frame 061033/0600 →
MERGER Recorded Dec 22, 2021
From: UNIVERSITE PARIS SUD
To: UNIVERSITÉ PARIS-SACLAY
Reel/Frame 058458/0634 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 19, 2021
From: SAUDOU, FREDERIC; VIRLOGEUX, AMANDINE
To: UNIVERSITÉ GRENOBLE ALPES; INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE; CENTRE HOSPITALIER UNIVERSITAIRE GRENOBLE ALPES; UNIVERSITE PARIS SUD
Reel/Frame 057234/0206 →
Priority Claims (1)
FR 1901773 · Feb 21, 2019 · national
Continuity (1)
Related Publication 20230181574A1 · Jun 15, 2023
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