Methods and compositions of anti-inflammatory drug and dicer activator for treatment of neuronal diseases
Inventors
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Publication Number
US-10980780-B2
Publication Date
2021-04-20
Expiration Date
Abstract
The present invention discloses compositions, means and kits thereof for treating neuronal clinical indications in a mammalian subject. The composition comprises, inter alia, a synergistic combination of an anti-inflammatory drug and a DICER activator. The present invention further discloses methods for treating neuronal diseases including Motor neuron diseases (MNDs), ALS, FTD (Frontotemporal Dementia), macular degeneration (AMD) autism, and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.
Core Innovation
The disclosed invention relates to compositions, means, kits, and methods for treating neuronal diseases using a synergistic combination of an anti-inflammatory drug and a DICER activator. The anti-inflammatory drug includes a COX-2 inhibitor, such as celecoxib, and the DICER activator includes fluoroquinolones such as ciprofloxacin and ciprofloxacin-HCl. The combination is presented as a therapeutically effective synergistic combination for slowing or inhibiting progression of amyotrophic lateral sclerosis.
The disclosure frames the problem as neuronal diseases in which a treatment is sought that can slow or inhibit progression, with amyotrophic lateral sclerosis and motor neuron diseases specifically addressed. It also provides broad disease indications including FTD, autism, AMD, Parkinson’s, and Alzheimer’s, alongside defining drug classes, DICER function, and the role of microRNA/miRNA biogenesis and RNA interference/RISC in the context of DICER activation.
The invention defines administration routes and formulation types and includes anti-inflammatory:DICER activator weight/weight ratio ranges, including about 10:1 to about 1:1000. Preclinical zebrafish ALS results are described using SOD1 G93R, where celecoxib and ciprofloxacin combination improves locomotor activity and nearly restores motor neuron axonopathy, while individual treatments show lesser effects. The disclosure also compares ciprofloxacin versus enoxacin as DICER enhancers.
Claims Coverage
The independent claims identified in the provided claim list comprise a method claim focused on treating amyotrophic lateral sclerosis using a therapeutically effective synergistic combination of celecoxib and ciprofloxacin that slows or inhibits disease progression. Main inventive features are concentrated in the specific drug combination, the synergistic therapeutically effective amount, and further refinements in dependent claim language.
Synergistic combination for ALS progression inhibition
Administering to a subject a formulation comprising a therapeutically effective amount of synergistic combination of celecoxib and ciprofloxacin, wherein the therapeutically effective amount slows or inhibits progression of amyotrophic lateral sclerosis in the subject.
Celecoxib-to-ciprofloxacin ratio constraint
Providing a celecoxib-to-ciprofloxacin ratio that ranges from about 10:1 to about 1:1000.
Sequential or concomitant administration
Administering celecoxib and ciprofloxacin either sequentially or concomitantly.
Oral administration to an ALS subject
Administering the formulation orally to a subject with amyotrophic lateral sclerosis.
Celecoxib and ciprofloxacin daily dose ranges
Using a celecoxib daily dose of about 10 mg to about 800 mg and a ciprofloxacin daily dose of about 50 mg to about 2000 mg daily.
Ciprofloxacin salt form
Specifying that the ciprofloxacin used is ciprofloxacin-HCl.
Across the independent-method claim and its refinements, the coverage centers on administering a therapeutically effective synergistic combination of celecoxib and ciprofloxacin to slow or inhibit amyotrophic lateral sclerosis progression, with additional inventive constraints including ratio ranges, administration timing, oral route, celecoxib/ciprofloxacin daily dose ranges, and ciprofloxacin-HCl salt form.
Stated Advantages
Slows or inhibits progression of amyotrophic lateral sclerosis in the subject.
Notably improves locomotor activity when celecoxib and ciprofloxacin are used in combination in a preclinical zebrafish ALS model.
Nearly restores motor neuron axonopathy in the preclinical zebrafish ALS model when used in combination.
Documented Applications
Treatment use case for a subject having amyotrophic lateral sclerosis using a formulation comprising a therapeutically effective synergistic combination of celecoxib and ciprofloxacin.
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