Use of alpha-1-antitrypsin for the preparation of drugs for the treatment of chronic fatigue syndrome
Inventors
Garcia Quintana, Ana • Alegre Martin, José
Assignees
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Publication Number
US-9205134-B2
Publication Date
2015-12-08
Expiration Date
Abstract
The present invention relates to the use of alpha-1-antitrypsin for the preparation of effective drugs for the treatment of chronic fatigue syndrome. In addition, the present invention relates to the use of plasma or other therapeutic forms with an alpha-1-antitrypsin content sufficient to obtain a dose of 6 mg or more of alpha-1-antitrypsin per kg of body weight at a frequency of between 1 and 31 days.
Core Innovation
The invention relates to a method for treating cognitive impairment in a patient suffering from chronic fatigue syndrome by administering alpha-1-antitrypsin (AAT). The method includes using plasma, recombinant, or recomposed therapeutic forms of AAT to provide a dose sufficient to reduce cognitive impairment.
The described approach links AAT to CFS immunobiology in peripheral blood mononuclear cells (PBMCs). The document states that AAT inhibits elevated intracellular elastase in patient PBMCs and reduces RNase L proteolysis, maintaining an 83 kDa/37 kDa RNase L ratio below 0.5.
The document also states that AAT modulates gene expression in PBMCs, including increasing 2-5A synthetase and SERPINA1 while decreasing metallothionine genes. The document further describes serum exposure as part of the treatment concept, including a serum level up to 8× baseline at 24 hours, and lists administration routes including intravenous/parenteral, intramuscular/intradermal, and inhalation.
Claims Coverage
The partial content identifies one independent claim covering treating cognitive impairment in chronic fatigue syndrome with alpha-1-antitrypsin, with dependent claims adding quantitative thresholds and administration details. The inventive features focus on the therapeutic purpose, administering AAT at a sufficient dose, and claim refinements using biomarker, dose, serum exposure, route, and regimen constraints.
Treating cognitive impairment in chronic fatigue syndrome with alpha-1-antitrypsin
A method for treating cognitive impairment in a patient suffering from chronic fatigue syndrome comprising administering to said patient alpha-1-antitrypsin at a dose sufficient to reduce said cognitive impairment.
Biomarker-guided RNase L ratio reduction in PBMCs
Administering alpha-1-antitrypsin at a dose sufficient to lower the 83 kDa RNase L to 37 kDa RNase L ratio to below 0.5 in peripheral blood mononuclear cells from the patient.
Minimum AAT dose threshold for cognitive impairment reduction
Administering alpha-1-antitrypsin to a patient at a dose greater than 6 mg/kg body weight to reduce cognitive impairment.
Serum exposure target after administration
Administering alpha-1-antitrypsin to reach a patient serum level up to eight times above baseline levels 24 hours after administration.
Route-limited administration of alpha-1-antitrypsin
Administering alpha-1-antitrypsin to the patient via one of several routes: parenteral, intravenous, intramuscular, intradermal, or inhalation.
Weekly repeated dosing regimen within a specified range
Administering alpha-1-antitrypsin to the patient at a dose of 25 to 60 mg/kg body weight, repeated at least once weekly for 8 weeks, to reduce cognitive impairment.
Across the independent claim and its dependents, the core claim covers administering alpha-1-antitrypsin at a dose sufficient to reduce cognitive impairment in chronic fatigue syndrome, with dependent claim inventive features specifying PBMC RNase L ratio reduction below 0.5, minimum dose thresholds, achieved serum level timing, allowable administration routes, and a weekly dosing regimen over 8 weeks.
Stated Advantages
Reduces cognitive impairment in a patient suffering from chronic fatigue syndrome.
Reduces PBMC elastase and reduces RNase L proteolysis, maintaining an 83 kDa/37 kDa RNase L ratio below 0.5.
Modulates PBMC gene expression by increasing 2-5A synthetase and SERPINA1 and decreasing metallothionine genes.
Is associated with improved fatigue, exercise tolerance, and cognition in a CFS patient in the compassionate-use example.
Documented Applications
Treating cognitive impairment in a patient suffering from chronic fatigue syndrome using alpha-1-antitrypsin administration.
Compassionate-use treatment in a CFS patient with weekly intravenous alpha-1-antitrypsin associated with improved fatigue, exercise tolerance, and cognition.
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