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Ppar[gamma] agonist for treatment of progressive supranuclear palsy

一种预防性、对象的技术，应用在神经系统疾病、化合物筛选/测试、药物组合等方向，能够解决药物无法充分减轻症状等问题

Inactive Publication Date: 2020-04-10
COHERUS BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as the disease progresses and symptoms worsen, the drug may not adequately reduce symptoms

Method used

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  • Ppar[gamma] agonist for treatment of progressive supranuclear palsy
  • Ppar[gamma] agonist for treatment of progressive supranuclear palsy
  • Ppar[gamma] agonist for treatment of progressive supranuclear palsy

Examples

Experimental program
Comparison scheme
Effect test

specific Embodiment approach

[0084] New uses for known compounds that modulate PPARγ have now been discovered. In particular, PPARγ agonists, particularly INT131, have been found to be effective in the treatment of progressive supranuclear palsy.

[0085] Accordingly, in one embodiment, the present invention relates to a method of treating progressive supranuclear palsy or a symptom thereof in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of INT131 or a pharmaceutically acceptable salt thereof, Pharmaceutical compositions of prodrugs or isomers.

[0086] Without wishing to be bound by a particular theory, it is believed that INT131 increases PPARγ activation in brain cells (including activation of elements in the PPARγ pathway), increases adiponectin levels, improves energy metabolism in brain cells, and reduces or prevents abnormal Tau protein activation. aggregation, by reducing oxidative stress and neuroinflammation, and thus treating progressiv...

Embodiment 1

[0205] Example 1: INT131 is a potent adiponectin upregulator in patients with reduced adiponectin levels

[0206] method

[0207] A randomized, double-blind, placebo-controlled 24-week study was conducted in which adiponectin levels were measured. The study had a 2-week run-in period, a 24-week double-blind treatment period and a 2-week follow-up period. 367 patients with type 2 diabetes mellitus (TD2), a disease in which patients have reduced adiponectin levels, were randomly assigned to receive 0.5, 1, 2, or 3 milligrams ("mg") of INT131 besylate, 45 mg of pioglitazone or placebo for 24 weeks. To measure adiponectin levels, blood was drawn at weeks 0, 2, 6, 12 and 24.

[0208] The results of the study showed that INT131 at doses of 1, 2 and 3 mg resulted in HbA compared with placebo 1c level was statistically significantly lower. Furthermore, the study showed that INT131 at doses of 2 mg and 3 mg reduced HbA 1c Levels at least consistent with 45 mg of pioglitazone, a...

Embodiment 2

[0220] Example 2: INT131 is a potent upregulator of adiponectin in healthy subjects

[0221] method

[0222] A study was conducted to determine the effect of INT131 on serum adiponectin levels. 30 healthy subjects were randomly selected to receive placebo, 0.1mg INT131, 1mg INT131 or 4mg INT131 daily for 14 days. To measure adiponectin levels, blood was drawn on days 1, 4, 8 and 14.

[0223] result

[0224] From day 1 to day 14, administration of placebo and 0.1 mg INT131 did not significantly change serum adiponectin levels, and further administration of 0.1 mg INT131 resulted in no significant change in adiponectin levels compared to placebo. See figure 1 . However, administration of 1 mg or 4 mg INT131 resulted in significant changes in serum adiponectin levels relative to placebo and from day 1 to day 14. Thus, administration of INT131 is capable of upregulating adiponectin in healthy individuals (ie, subjects without reduced adiponectin levels due to disease or d...

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Abstract

Methods of treatment of progressive supranuclear palsy or its symptoms, with PPAR[gamma] agonists, and in particular, the compound of formula (I) known as INT 131: Formula (I). Also provided are methods of treating a subject that include selecting a subject having an elevated level of neurofilament light chain protein in a sample obtained from the subject, as compared to a reference level of neurofilament light chain protein, and administering a pharmaceutical composition including a therapeutically effective amount of a compound of formula (I) to the selected subject.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 480,838, filed April 3, 2017, and U.S. Provisional Patent Application Serial No. 62 / 651,653, filed April 2, 2018, the contents of each of which are incorporated by reference in their entirety This article. [0003] field of invention [0004] The present invention relates to a method for treating progressive supranuclear palsy. The invention also relates, at least in part, to methods of using CHS-131 to treat a subject having an elevated level of neurofilament light chain protein (e.g., compared to a reference level of neurofilament light chain protein) in a sample comprising Cerebrospinal fluid, blood, serum or plasma of the subject. Background technique [0005] Neurological disorders can cause permanent and irreversible damage that can affect a patient's quality of life, such as language, cognitive skills, motor skills, and metabo...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/47A61P25/28
CPCA61K31/47A61P25/28A61P25/00A61K49/0004
Inventor B·芬克D·E·维因斯泰恩S·K·贾殷
Owner COHERUS BIOSCI
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