Methods for treating heart disease in a subject with Friedreich's ataxia by an aromatic-cationic peptide

Inventors

Wilson, D. Travis

Assignees

Stealth Biotherapeutics Inc

Abstract

The disclosure provides methods of preventing or treating Friedreich's ataxia in a mammalian subject, reducing risk factors, signs and/or symptoms associated with Friedreich's ataxia, and/or reducing the likelihood or severity of Friedreich's ataxia. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide to e.g., reduce oxidative stress, increase mitochondrial metabolism, or a combination thereof.

Core Innovation

The problem addressed is treating or preventing Friedreich’s ataxia and related frataxin deficiency, which is associated with oxidative stress and reduced mitochondrial function. In subjects having Friedreich’s ataxia, the document links frataxin deficiency to mitochondrial dysfunction, including oxidative stress/reactive oxygen species and impaired mitochondrial metabolism, mitochondrial membrane potential, mitochondrial iron handling, and mitochondrial frataxin localization to mitochondria. The invention targets these deficiencies by administering an aromatic-cationic peptide as a therapeutic approach.

The core approach is administering an aromatic-cationic peptide, exemplified by D-Arg-2′,6′-Dmt-Lys-Phe-NH2, or a pharmaceutically acceptable salt thereof, to subjects having Friedreich’s ataxia. The document states that therapeutic effects are associated with reducing oxidative stress/ROS, stabilizing and/or increasing mitochondrial metabolism, restoring mitochondrial membrane potential, improving mitochondrial frataxin localization to mitochondria, and reducing mitochondrial iron. The therapeutic mechanism is also described as impacting processes related to mitochondrial iron overload and downstream cell death pathways, including caspase activation and apoptosis.

The document further applies the peptide treatment to heart disease in subjects having Friedreich’s ataxia. It describes that the therapeutic method addresses heart disorders associated with Friedreich’s ataxia, including heart rhythm abnormalities such as tachycardia and heart block. The peptide can be used as monotherapy and is also described in the context of optional combination therapy with additional therapeutic agents, with an asserted synergistic effect when the peptide is administered together with an additional therapeutic agent.

Claims Coverage

The partial content identifies one independent claim. It covers one inventive concept: treating heart disease in a subject having Friedreich’s ataxia by administering a therapeutically effective amount of a specific aromatic-cationic peptide (or a pharmaceutically acceptable salt).

Across the identified claim coverage, the core inventive feature is the use of D-Arg-2′,6′-Dmt-Lys-Phe-NH2 (or a pharmaceutically acceptable salt) to treat heart disease in subjects having Friedreich’s ataxia, with further refinements including minimum daily treatment durations, optional combination therapy with selected additional therapeutic agents, an asserted synergistic effect, and narrowing to tachycardia or heart block.

Stated Advantages

Documented Applications