Methods for improving exercise tolerance in myalgic encephalomyelitis patients
Inventors
Strayer, David R. • YOUNG, DIANE L. • EQUELS, Thomas K.
Assignees
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Publication Number
US-11813281-B2
Publication Date
2023-11-14
Expiration Date
Abstract
The present invention relates to methods for treating a subject with myalgic encephalomyelitis/chronic fatigue syndrome symptoms comprising administering a target subject a pharmaceutical composition comprising a therapeutic dsRNA (tdsRNA).
Core Innovation
The invention relates to a method for treating a subject with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) symptoms by determining that the subject is a target subject exhibiting onset of ME/CFS symptoms between 2 to 8 years prior to treatment, and administering to the target subject a pharmaceutical composition comprising an effective amount of therapeutic dsRNA (tdsRNA) as an active ingredient.
The therapeutic dsRNA is defined in terms of structure and sequence/length, including rI_n·r(C12U)_n and n being an integer from 40 to 50,000. The invention also includes further characterization of the tdsRNA composition and properties, including constraints tied to dsRNA size distribution, helical turns, and molecular weight ranges.
The patient selection and treatment evaluation are linked to functional outcomes in ME/CFS, including exercise treadmill tolerance improvements and PEM-related considerations as part of defining target subjects. The disclosed approach reports improved exercise treadmill tolerance outcomes associated with tdsRNA treatment, including responder rates and placebo-adjusted differences, and references quality-of-life relevance and tolerability statements.
Claims Coverage
The independent claim covers a two-part treatment method for ME/CFS that first determines a target-subject timing window (2 to 8 years since onset) and then administers an effective amount of a specific therapeutic dsRNA defined by rI_n·r(C12U)_n with n from 40 to 50,000. The claim set refines target selection and treatment outcomes through additional inventive features including PEM duration and quantitative exercise-tolerance improvement, and through formulation constraints on dsRNA composition and physicochemical properties (e.g., size distribution and molecular weight).
Target-subject symptom-onset window and tdsRNA administration
A method for treating a subject with ME/CFS symptoms comprising determining the subject is a target subject exhibiting onset of ME/CFS symptoms between 2 to 8 years prior to treatment and administering to the target subject a pharmaceutical composition comprising an effective amount of therapeutic dsRNA (tdsRNA).
rI_n·r(C12U)_n therapeutic dsRNA with n constrained
The method wherein the tdsRNA is rI_n·r(C12U)_n and wherein n is an integer from 40 to 50,000.
PEM-duration refinement for target subject
The method wherein the target subject experiences post-exertional malaise (PEM) lasting about 24 hours or longer.
Quantified exercise tolerance improvement (≥25%)
The method wherein the target subject is treated such that it increases exercise tolerance by at least 25% after treatment compared with before treatment.
High fraction of dsRNA larger than 40 bp
The method wherein the tdsRNA formulation contains at least 90 weight percent of dsRNA larger than 40 base pairs.
Molecular-weight range for tdsRNA
The method wherein the tdsRNA has a molecular weight in the range of about 10 kilodaltons to about 30,000 kilodaltons.
Listed stabilizing polymer options
The method wherein a stabilizing polymer is chosen from polylysine, polylysine plus carboxymethylcellulose, polyarginine, polyarginine plus carboxymethylcellulose, poly ICLC, or combinations thereof.
Overall, the claim coverage is grounded in treating ME/CFS symptoms by targeting a symptom-onset timing window (2 to 8 years), administering a defined therapeutic dsRNA (rI_n·r(C12U)_n with n from 40 to 50,000), and optionally refining the target-subject definition using PEM duration and quantified exercise-tolerance response. Additional coverage narrows tdsRNA composition and properties, including dsRNA size distribution and molecular-weight constraints, and specifies optional stabilizing polymer choices.
Stated Advantages
Improved exercise treadmill tolerance outcomes with a reported responder rate and placebo-adjusted differences.
Treatment is associated with functional improvement in exercise tolerance and is linked to quality-of-life relevance.
Tolerability statements are provided in connection with the improved exercise-tolerance outcome.
Documented Applications
Use in a ME/CFS placebo-controlled trial context using tdsRNA treatment, with exercise treadmill tolerance as an outcome and responder definition based on ≥25% exercise improvement.
Patient stratification by symptom-onset duration (2–8 years) to identify a responsive subset in ME/CFS.
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