Compositions for improving cell viability and methods of use thereof
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Publication Number
US-12186330-B2
Publication Date
2025-01-07
Expiration Date
Abstract
This invention relates to methods and compositions for use improving cell viability, particularly neural cell viability, and more particularly to methods and compositions for use improving cell viability by reducing reactive oxygen metabolite-mediated oxidative damage in a cell, regulating redox homeostasis in a cell, or reducing mitochondrial dysfunction in a cell. The invention further relates to the administration of the bile acid tauroursodeoxycholic acid (TUDCA) in combination with phenylbutyric Acid (PBA) to improve cell viability, and treat at least one symptom associated with, prevent the time of onset of, or slow the development of a disease related to oxidative stress.
Core Innovation
The disclosed concept aims to improve neural viability by reducing reactive oxygen metabolite-mediated oxidative damage. It regulates redox homeostasis and/or reduces mitochondrial dysfunction, thereby mitigating oxidative stress-associated neuronal injury and cell death processes. The described context includes oxidative damage and apoptosis under oxidative stress conditions.
The disclosure highlights a therapeutic synergy involving tauroursodeoxycholic acid (TUDCA) together with phenylbutyric acid (PBA) and/or 4-phenylbutyric acid (4-PBA). It describes greater-than-additive effects in peroxide (H2O2)-challenged rat cortical neurons, with outcomes assessed using cell viability and cell death readouts. Reactive oxygen metabolite-mediated oxidative damage is positioned as a target pathway influenced by the combination.
The document further relates the approach to treating neurodegenerative diseases related to oxidative stress, including Alzheimer’s disease and amyloidosis/amyloid plaques, and associated tau pathology such as phosphorylated tau. It also describes patient stratification using APOE4 allele presence and administering the agents in combination, including reducing the PBA dose in combination versus PBA alone.
Claims Coverage
Two independent claims are identified. Across these claims, the inventive coverage centers on treating at least one symptom of a tauopathy by administering TUDCA together with sodium phenylbutyrate at defined amounts, schedules, and regimen phases.
Combination dosing of TUDCA and sodium phenylbutyrate for tauopathy symptoms
Administering to a subject about 10 mg/kg to about 30 mg/kg of body weight of tauroursodeoxycholic acid (TUDCA) and about 30 mg/kg to about 100 mg/kg of body weight of sodium phenylbutyrate to treat at least one symptom of a tauopathy.
Once-daily to twice-daily phased regimen for tauopathy symptoms
Administering about 1 gram of TUDCA once a day and about 3 grams of sodium phenylbutyrate once a day for at least about 2 weeks, followed by administering about 1 gram of TUDCA twice a day and about 3 grams of sodium phenylbutyrate twice a day for treating at least one symptom of a tauopathy.
The independent claims cover combination dosing of TUDCA and sodium phenylbutyrate within specified body-weight ranges and a phased regimen that transitions from once-daily dosing to twice-daily dosing. Dependent claim refinements further address administration format, schedule details, duration constraints, and route limitations.
Stated Advantages
Documented Applications
No documented applications found
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