Methods of treatment of temozolomide-resistant glioma using coenzyme Q10
Inventors
Narain, Niven Rajin • Sarangarajan, Rangaprasad • VISHNUDAS, VIVEK K. • Diers, Anne R. • Gesta, Stephane
Assignees
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Publication Number
US-12303471-B2
Publication Date
2025-05-20
Expiration Date
Abstract
The invention provides methods and compositions for treatment of a subject with a glioma that has failed treatment with temozolomide (TMZ) comprising administration of a composition comprising a Coenzyme Q10 compound to the subject. The invention also provides a method of treating a cancer that exhibits increased Complex II activity in a subject comprising administration of a composition comprising a Coenzyme Q10 compound to the subject.
Core Innovation
The invention relates to treating a glioma in a subject by administering a composition comprising a Coenzyme Q10 compound together with temozolomide (TMZ). The Coenzyme Q10 compound is delivered by injection or infusion, and the approach is directed to glioma treatment in which TMZ is used in combination with increased mitochondrial Complex II activity associated with Coenzyme Q10.
The background problem described in the provided content is the treatment challenge presented by temozolomide (TMZ)-resistant or refractory glioma and other cancers, including glioblastoma. The document indicates that prior TMZ failure and related limitations motivate a therapeutic strategy that links CoQ10 cytotoxicity and apoptosis to Complex II-driven respiration, with Complex II identified as succinate-coenzyme Q reductase (SDH; EC 1.3.5.1).
The document further supports the treatment concept with described assessment of clinical benefit and embodiments for glioblastoma populations and combinations. Clinical benefit is assessed using RECIST 1.1 response categories including stable disease, partial response, and complete response, and the provided content also describes combination possibilities with bevacizumab and delivery/formulation concepts including intravenous infusion and nanosuspension formulations for CoQ10.
Claims Coverage
The independent claim is directed to a TMZ combination treatment for glioma using a Coenzyme Q10 compound delivered by injection or infusion. The dependent claims further refine glioma types and stages, clinical benefit selection, and delivery specifics, including continuous infusion and duration thresholds, as well as an optional addition of bevacizumab.
Glioma treatment with Coenzyme Q10 and temozolomide
A method of treating a glioma in a subject by administering a composition comprising a Coenzyme Q10 compound and temozolomide (TMZ), thereby treating the glioma in the subject.
Injection or infusion delivery of Coenzyme Q10 composition
The composition comprising the Coenzyme Q10 compound is administered by injection or infusion.
Coenzyme Q10 dose selected from specified minimum mg/kg/dose options
The method further specifies that a Coenzyme Q10 dose is selected from specified minimum mg/kg/dose options.
Continuous infusion administration of Coenzyme Q10 composition
The method further specifies that a composition containing Coenzyme Q10 is administered via continuous infusion.
Continuous infusion duration thresholds for Coenzyme Q10 administration
The method of administering by continuous infusion provides that the composition containing Coenzyme Q10 is administered for at least specified durations including 48, 72, 96, 120, or 144 hours.
RECIST 1.1-defined clinical benefit categories
The method further specifies that clinical benefit is chosen from stable disease, partial response, or complete response as defined by RECIST 1.1 criteria.
Addition of bevacizumab
The method further includes using the additional anti-cancer agent bevacizumab.
Claim coverage centers on administering a Coenzyme Q10 compound in combination with temozolomide for treating a glioma, with delivery by injection or infusion. Dependent claim refinements include specified CoQ10 dose options, continuous infusion delivery and minimum infusion durations, RECIST 1.1-based clinical benefit categories, and inclusion of bevacizumab as an additional anti-cancer agent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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