US 12,403,104 B2
Compounds and methods of promoting myelination
Paul J. Tesar, Wickliffe, OH (US); Drew Adams, Cleveland, OH (US); Zita Hubler, Cleveland, OH (US); Matthew Elitt, St. Louis, MO (US); Dharmaraja Allimuthu, Cleveland, OH (US); and Steven B. Landau, Wellesley, MA (US)
Assigned to Case Western Reserve University, Cleveland, OH (US)
Filed by Case Western Reserve University, Cleveland, OH (US)
Filed on May 27, 2022, as Appl. No. 17/826,252.
Application 17/826,252 is a division of application No. 16/320,554, granted, now 11,344,511, previously published as PCT/US2017/044205, filed on Jul. 27, 2017.
Claims priority of provisional application 62/452,204, filed on Jan. 30, 2017.
Claims priority of provisional application 62/367,416, filed on Jul. 27, 2016.
Prior Publication US 2023/0000798 A1, Jan. 5, 2023
Int. Cl. A61K 31/137 (2006.01); A61K 31/136 (2006.01); A61K 31/138 (2006.01); A61K 31/198 (2006.01); A61K 31/4174 (2006.01); A61K 31/4196 (2006.01); A61K 31/4535 (2006.01); A61K 31/4545 (2006.01); A61K 31/496 (2006.01); A61K 31/5375 (2006.01); A61K 31/7105 (2006.01); A61K 38/16 (2006.01); A61K 38/21 (2006.01); A61K 39/395 (2006.01); A61K 45/06 (2006.01); A61P 25/14 (2006.01); A61P 25/28 (2006.01); C12N 9/50 (2006.01); C12N 15/113 (2010.01)
CPC A61K 31/137 (2013.01) [A61K 31/136 (2013.01); A61K 31/138 (2013.01); A61K 31/198 (2013.01); A61K 31/4174 (2013.01); A61K 31/4196 (2013.01); A61K 31/4535 (2013.01); A61K 31/4545 (2013.01); A61K 31/496 (2013.01); A61K 31/5375 (2013.01); A61K 31/7105 (2013.01); A61K 38/16 (2013.01); A61K 38/215 (2013.01); A61K 39/3955 (2013.01); A61K 45/06 (2013.01); A61P 25/14 (2018.01); A61P 25/28 (2018.01); C12N 9/50 (2013.01); C12N 15/1137 (2013.01)] 10 Claims
 
1. A method of treating multiple sclerosis (MS), amylotrophic lateral sclerosis (ALS), Alzheimer's disease, Huntington's disease, or Parkinson's disease in a subject wherein myelination or remyelination is beneficial to the subject, the method comprising administering to the subject a therapeutically effective amount of an agent that inhibits expression of an enzyme that synthesizes one or more sterol intermediates of the cholesterol biosynthesis pathway in oligodendrocyte progenitor cells (OPCs), wherein the agent:
(1) comprises an interfering RNA targeting said enzyme, or an antisense oligonucleotide targeting said enzyme, or
(2) a polynucleotide encoding said interfering RNA, or said antisense oligonucleotide;
wherein said enzyme functions in the cholesterol biosynthesis pathway spanning CYP51 and emopamil binding protein (EBP).