Method of treating immunoglobulin light chain amyloidosis
Inventors
Diomede, Luisa • SALMONA, Mario • Merlini, Giampaolo
Assignees
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Publication Number
US-11357770-B2
Publication Date
2022-06-14
Expiration Date
Abstract
The present invention relates to the use of substituted quinoline compounds for treating immunoglobulin light chain (LC) amyloidosis (AL), especially cardiotoxicity associated with immunoglobulin LC AL. In particular, the substituted quinoline compounds useful in the treatment of cardiac LC amyloidosis are 5,7-dihalo-8-hydroxyquinoline derivatives, especially 5,7-dichloro-8-hydroxyquinoline derivatives.
Core Innovation
The disclosure describes substituted quinoline compounds, including 5,7-dihalo-8-hydroxyquinoline derivatives such as 5,7-dichloro-8-hydroxyquinoline derivatives, for treating or preventing immunoglobulin light chain (AL) amyloidosis. The compounds are defined as compounds of formula (I), including pharmaceutically acceptable salts, hydrates, and solvates.
The document frames an anti-cardiotoxicity therapeutic concept centered on compound-mediated metal/ROS involvement. It references assays indicating superoxide and hydrogen peroxide, and describes comparison between cardiotoxic immunoglobulin light chains and myeloma light chain controls.
The disclosure states that the substituted quinoline compounds can alleviate or reverse symptoms and protect against heart tissue damage associated with cardiotoxic immunoglobulin light chains. It also describes modulation of the FOXO/DAF-16 signaling pathway and oxidative-stress genes, and reports mitochondrial ultrastructural damage in C. elegans and in AL patient biopsies.
Claims Coverage
The partial content includes three independent claims centered on administering a compound of formula (I) to treat immunoglobulin light chain amyloidosis, with refinements to cardiotoxicity associated with immunoglobulin light chain amyloidosis and an antioxidant combination. Across the independent claims, the inventive coverage is organized around the broad formula (I) compound definition with enumerated substituent options and allowed salts, hydrates, and solvates.
Administering a compound of formula (I) to treat immunoglobulin light chain amyloidosis
A method of treating immunoglobulin light chain amyloidosis in a subject in need thereof comprising administering a compound of formula (I) having substituent definitions for R, R1, R3, R2, R4, R5, R6, R7, R8, R9, R10, R11, and m (m is 0 or 1), including pharmaceutically acceptable salt, hydrate or solvate thereof.
Treating cardiotoxicity symptoms associated with immunoglobulin light chain amyloidosis using a compound of formula (I)
A method of treating or alleviating or reversing the symptoms of cardiotoxicity associated with immunoglobulin light chain amyloidosis in a subject in need thereof comprising administering a compound of formula (I) with the same substituent definitions, including pharmaceutically acceptable salt, hydrate or solvate thereof.
Treating immunoglobulin light chain amyloidosis symptoms with a compound of formula (I) and an antioxidant
A method of treating or alleviating or reversing the symptoms of immunoglobulin light chain amyloidosis comprising administering an effective amount of a compound of formula (I) with the same substituent definitions, including pharmaceutically acceptable salt, hydrate or solvate thereof; and an effective amount of an antioxidant.
Across the independent claims, the inventive coverage consistently requires administering compounds of formula (I) defined by broad enumerated substituent options, with permitted pharmaceutically acceptable salts, hydrates, and solvates. The claims differ in therapeutic scope: one treats immunoglobulin light chain amyloidosis generally, one targets cardiotoxicity associated with immunoglobulin light chain amyloidosis with alleviation or reversal of cardiotoxicity symptoms, and one adds treatment, alleviation, or reversal of immunoglobulin light chain amyloidosis symptoms in combination with an antioxidant.
Stated Advantages
Alleviating or reversing symptoms of immunoglobulin light chain amyloidosis.
Treating or alleviating or reversing the symptoms of cardiotoxicity associated with immunoglobulin light chain amyloidosis.
Combination treatment with an antioxidant as part of treating, alleviating, or reversing immunoglobulin light chain amyloidosis symptoms.
Documented Applications
Treating immunoglobulin light chain amyloidosis in a subject in need thereof.
Treating, alleviating, or reversing symptoms of cardiotoxicity associated with immunoglobulin light chain amyloidosis.
Treating, alleviating, or reversing symptoms of immunoglobulin light chain amyloidosis using an effective amount of a compound of formula (I) together with an antioxidant.
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