Method of treating or preventing tumors of the central nervous system
Inventors
Jimenez, Joaquin J. • Narain, Niven Rajin • Sarangarajan, Rangaprasad • McCook, John Patrick
Assignees
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Publication Number
US-10376477-B2
Publication Date
2019-08-13
Expiration Date
Abstract
The invention provides methods and compositions for treatment of a subject with a central nervous system (CNS) tumor comprising administration of Coenzyme Q10 (CoQ10), particularly when the subject exhibits at least one CNS abnormality as a result of the tumor.
Core Innovation
The invention relates to methods of treating a central nervous system (CNS) tumor in a subject exhibiting at least one CNS abnormality as a result of the presence of the CNS tumor. The method administers a composition comprising a Coenzyme Q10 (CoQ10) compound to treat the CNS tumor, and at least one CNS abnormality includes difficulty with walking, with treatment resulting in amelioration of the difficulty with walking in the subject.
The disclosed subject matter includes embodiments directed to CNS abnormalities exhibited by the subject as a result of the presence of the CNS tumor, including neurological and cognitive symptoms such as headache, seizure, change in memory, change in temperament, confusion, disorientation, blurred vision, loss of vision, loss of peripheral vision, double vision, dizziness, hearing problems, decreased muscle control, lack of coordination, decreased sensation, weakness, paralysis, paraplegia, quadriplegia, change in gait, and difficulty with speech.
The invention also describes treatment of different CNS tumor contexts, including primary CNS tumor, secondary CNS tumor, metastatic tumor, leukemic tumor, chloroleukemia, and pediatric tumors, with disclosed embodiments including remission. In certain embodiments, CoQ10 treatment is combined with additional tumor therapies such as chemotherapy, radiation therapy, and/or surgery, and CoQ10 is administered by non-intracranial administration, including intravenous administration.
In disclosed formulations, CoQ10 is provided as an intravenous nanosuspension comprising nano-particles with a mean particle size less than 200 nm, stabilized using a dispersion stabilizing agent and/or an opsonization reducer. Experimental support is described using a Fischer 344 rat chloroleukemia CNS model, where CoQ10-treated animals show recovered motor skills and regressed MRI-detectable lesions, supporting treatment and potential prophylaxis against secondary CNS tumor development.
Claims Coverage
The partial content provides one independent claim and describes dependent claims that refine subject symptoms, tumor types, combination therapies, and CoQ10 formulation parameters, including intravenous nanosuspension nanoparticle size and specific formulation component percentages.
Treating a CNS tumor with CoQ10 to ameliorate walking difficulty
A method of treating a central nervous system (CNS) tumor in a subject exhibiting at least one CNS abnormality as a result of the presence of the CNS tumor by administering to the subject a composition comprising a Coenzyme Q10 (CoQ10) compound, thereby treating the CNS tumor, wherein the at least one CNS abnormality comprises difficulty with walking and treatment results in amelioration of the difficulty with walking.
Enumerated CNS abnormalities including walking difficulty
The method where the at least one CNS abnormality exhibited by the subject comprises difficulty with walking and includes at least one neurological or cognitive symptom selected from an enumerated list of CNS abnormality types.
Leukemic tumor treatment
The method where the CNS tumor being treated is a leukemic tumor.
Combination with radiation therapy
The method where the CNS tumor is further treated with radiation therapy.
Intravenous CoQ10 nanosuspension with nanoparticles under 200 nm
The method where the CoQ10 compound is provided in an intravenous formulation as a nano-dispersion that forms nanoparticles with a mean particle size less than 200 nm, using a dispersion stabilizing agent and/or an opsonization reducer.
Specific weight-per-volume formulation of CoQ10, DMPC, and poloxamer 188
The method where the CoQ10 formulation has weight-per-volume of CoQ10, DMPC, and poloxamer 188 of 4%, 3%, and 1.5%, respectively.
Across the independent claim and the identified dependent refinements, the core coverage centers on administering a CoQ10 composition to treat a CNS tumor in subjects with CNS abnormalities that include difficulty with walking, with amelioration, and further specifies additional CNS symptom sets, leukemic/chloroleukemia contexts, optional combination with radiation therapy, and intravenous CoQ10 nanosuspension formulation constraints including nanoparticles with mean particle size less than 200 nm and example component weight-per-volume percentages.
Stated Advantages
Amelioration of difficulty with walking in the subject following treatment.
Recovered motor skills in CoQ10-treated animals in the disclosed Fischer 344 rat chloroleukemia CNS model.
Regression of MRI-detectable lesions in CoQ10-treated animals in the disclosed Fischer 344 rat chloroleukemia CNS model.
Potential prophylaxis against secondary CNS tumor development, as supported by the disclosed experimental support.
Documented Applications
Treating a central nervous system tumor in a subject exhibiting CNS abnormalities, including difficulty with walking.
Treating CNS tumor-related neurological and cognitive symptoms, including headache, seizure, change in memory, change in temperament, confusion, disorientation, and vision-related symptoms.
Treating primary CNS tumor and secondary CNS tumor contexts, including metastatic tumor, leukemic tumor, chloroleukemia, and pediatric tumors.
Use of CoQ10 treatment supported by a Fischer 344 rat chloroleukemia CNS model with recovered motor skills and regressed MRI-detectable lesions.
Potential prophylaxis against secondary CNS tumor development, as described by the disclosed experimental support.
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