Methods and compositions for treating amyotrophic lateral sclerosis
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Publication Number
US-12138272-B2
Publication Date
2024-11-12
Expiration Date
Abstract
Provided herein are methods for treating at least one symptom of ALS in a subject who has received a first dosage of BSEP inhibitor, the method including administering to the subject a composition comprising a bile acid or a pharmaceutically acceptable salt thereof and a phenylbutyrate compound, monitoring the subject for response to the B SEP inhibitor, and administering a second dosage of the BSEP inhibitor, wherein the second dosage is less than the first dosage.
Core Innovation
The invention relates to a method of administering Tauroursodiol (TURSO) and sodium phenylbutyrate to a human subject having at least one symptom of Amyotrophic Lateral Sclerosis (ALS) who has received a first dosage of cyclosporine. The method includes administering a composition comprising about 1 gram of TURSO and about 3 grams of sodium phenylbutyrate, and the subject has onset of at least one symptom of ALS for more than about 24 months.
The method includes determining serum transaminases and/or bilirubin in a first biological sample from the human subject. After that first determination, the method includes administering a second dosage of cyclosporine that is lower than the first dosage.
The document provides a rationale tied to transporter interaction and drug-drug interaction involving bile salt export pump (BSEP/ABCB11). It states that TURSO/phenylbutyrate metabolites can inhibit BSEP and that inhibition of BSEP can exacerbate liver conjugated bile salt accumulation when combined with BSEP inhibitors, so the second cyclosporine dosage is reduced and monitoring of transaminases/bilirubin is used.
Claims Coverage
The independent claim set covers 6 inventive features centered on ALS treatment with TURSO and sodium phenylbutyrate, cyclosporine dose reduction, and biomarker monitoring.
TURSO and sodium phenylbutyrate with reduced cyclosporine after biomarker determination in ALS
A method administering Tauroursodiol (TURSO) and sodium phenylbutyrate to a human subject having at least one symptom of Amyotrophic Lateral Sclerosis (ALS) who has received a first dosage of cyclosporine, comprising administering a composition comprising about 1 gram of TURSO and about 3 grams of sodium phenylbutyrate, determining a first level of serum transaminases and/or bilirubin in a first biological sample, and administering a second dosage of cyclosporine that is lower than the first dosage, wherein onset of at least one symptom of ALS is more than about 24 months and the first dosage of cyclosporine is about 0.5 to about 15 mg/kg/day.
Second cyclosporine-relevant biomarker determination using a second biological sample
The method further includes determining a second level of serum transaminases and/or bilirubin from a second biological sample taken from the human subject.
Comparative biomarker reduction relationship
Having a lower second level than a first level for serum transaminases and/or bilirubin.
Plasma or serum biological sample for biomarkers
Performing the method using a biological sample that is specifically a plasma or serum sample.
Once-daily TURSO administration
Specifying that TURSO is administered at an amount of about 1 gram once a day.
Oral or feeding-tube administration route
Administering the composition to a human subject orally or via a feeding tube.
Overall, the claims center on administering TURSO and sodium phenylbutyrate to an ALS human subject who has received cyclosporine, determining serum transaminases and/or bilirubin, and administering a second cyclosporine dosage that is lower than the first, with dependent claims refining biomarker re-measurement, comparative biomarker relationships, plasma or serum sample type, and route and dosing details.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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