Methods of treating rheumatic diseases using trimetazidine-based compounds
Inventors
Levin, Andrew D. • Gros, David-Alexandre • Patel, Jaikrishna
Assignees
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Publication Number
US-12318382-B2
Publication Date
2025-06-03
Expiration Date
Abstract
The invention provides compositions and methods for treating a subject having a rheumatic condition.
Core Innovation
The invention provides compositions and methods for treating a rheumatic disease, disorder, or condition in a subject by administering a compound represented by formula (X) or a compound represented by formula (IX). The treated condition is selected from a listed group of rheumatic diseases and related disorders, including ankylosing spondylitis, rheumatoid arthritis, pulmonary fibrosis, inflammatory myositis, and gout, and treatment is carried out by providing the compound-containing composition to a subject having the selected condition.
A central aspect is shifting cellular metabolism from fatty-acid oxidation to glucose oxidation and increasing mitochondrial respiration. The constructs include an NAD+ precursor, including nicotinic acid, nicotinamide, or nicotinamide riboside, and are supported by mechanistic rationale involving citric acid cycle intermediates and NAD/NADH cycling.
The disclosed compounds may be formed as covalently linked compounds or as combined separate components, including co-crystals. The summary also describes PEGylated or ethylene-glycol linker prodrug formats intended to improve bioavailability and potentially mitigate trimetazidine-associated Parkinsonian side effects by reducing CNS penetration and altering pharmacokinetics.
Claims Coverage
Two independent claims are directed to treating rheumatic diseases by providing compound-containing compositions, respectively using compounds of formula (X) or formula (IX). Across the claim set, the inventive features are the specific compound formulas paired with the defined rheumatic indication list, with dependent claims further specifying oral vs intravenous formulation and single-unit vs multi-unit dosing as additional refinements.
Treating rheumatic disease using a formula (X) compound composition
A method of treating a rheumatic disease, disorder, or condition in a subject by providing to a subject having the rheumatic disease, disorder, or condition a composition comprising a compound represented by formula (X), wherein the rheumatic disease, disorder, or condition is selected from the group consisting of ankylosing spondylitis, autoimmune-related lung disease, Behcet's Disease, bursitis, cachexia, cardiac fibrosis, claudication, dermatomyositis, frailty, gout, inflammatory arthritis, inflammatory eye disease, inflammatory myositis, juvenile idiopathic arthritis, muscle myopathy, myofascial pain syndrome, myositis, osteoarthritis, osteoporosis, polymyalgia rheumatica, polymyositis, psoriatic arthritis, pulmonary arterial hypertension, pulmonary fibrosis, rheumatoid arthritis, sarcopenia, scleroderma, Sjögren's syndrome, tendinitis, tinnitus, vasculitis, and vertigo.
Treating rheumatic disease using a formula (IX) compound composition
A method of treating a rheumatic disease, disorder, or condition in a subject by providing to a subject having the rheumatic disease, disorder, or condition a composition comprising a compound represented by formula (IX), wherein the rheumatic disease, disorder, or condition is selected from the group consisting of ankylosing spondylitis, autoimmune-related lung disease, Behcet's Disease, bursitis, cachexia, cardiac fibrosis, claudication, dermatomyositis, frailty, gout, inflammatory arthritis, inflammatory eye disease, inflammatory myositis, juvenile idiopathic arthritis, muscle myopathy, myofascial pain syndrome, myositis, osteoarthritis, osteoporosis, polymyalgia rheumatica, polymyositis, psoriatic arthritis, pulmonary arterial hypertension, pulmonary fibrosis, rheumatoid arthritis, sarcopenia, scleroderma, Sjögren's syndrome, tendinitis, tinnitus, vasculitis, and vertigo.
Claim coverage centers on treating rheumatic diseases by administering compositions containing compounds of formula (X) or formula (IX), with the treated condition selected from a defined rheumatic disease list. Dependent claims further narrow the treatment to specific routes of administration and dosing structures.
Stated Advantages
Improves bioavailability.
Potentially mitigates trimetazidine-associated Parkinsonian side effects by reducing CNS penetration and altering pharmacokinetics.
Documented Applications
Treatment of rheumatic diseases and conditions listed in the claims, including rheumatoid arthritis, ankylosing spondylitis, gout, inflammatory myositis, pulmonary fibrosis, and other enumerated conditions.
Mitochondrial function assessment concepts, including oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) profiling.
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