Compositions and methods for the treatment and prevention of neurological disorders

US11241417B2 · kind B2 · utility

Assignee

• Yumanity Therapeutics, Inc. · US

Inventors

• Rebecca ARON · Cambridge, US
• Bhaumik Pandya · Bedford, US
• Daniel TARDIFF · Arlington, US
• Jeff S. Piotrowski · Madison, US
• Matthew C. Lucas · Sunnyvale, US
• Bertrand Le Bourdonnec · Coatesville, US
• Kenneth Rhodes · Belmont, US
• Robert Scannevin · Hopkinton, US

Key dates

• Filing date: Jun 21, 2019
• Grant date: Feb 8, 2022
• Expiry date: Jun 21, 2039

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N15/1137
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention provides compositions and methods for treating neurological disorders, such as amyotrophic lateral sclerosis, frontotemporal degeneration, and Alzheimer's disease, among others. Using the compositions and methods described herein, a patient having a neurological disorder, such as a neurological disorder associated with TAR-DNA binding protein (TDP)-43 aggregation, may be administered an inhibitor of cytochrome P450 (CYP450) isoform 51A1 (CYP51A1), also referred to herein as lanosterol 14-alpha demethylase, so as to treat an underlying etiology of the disorder and/or to alleviate one or more symptoms of the disease. The inhibitor of CYP51A1 may be a small molecule, anti-CYP51A1 antibody or antigen-binding fragment thereof, or a compound, such as an interfering RNA molecule, that attenuates CYP51A1 expression. Patients that may be treated using the compositions and methods described herein include those that express a mutant TDP-43 isoform containing a mutation associated with TDP-43-promoted aggregation and toxicity.