Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy
AssigneeEntrada Therapeutics, Inc.
InventorsNatarajan Sethuraman, Jason Ruth, Louis A. Tartaglia, Dehua Pei, Ziqing Qian
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Abstract
Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.
Claims22
A method of treating Mitochondrial Neurogastrointestinal Encephalopathy (MNGIE) in an individual in need thereof, comprising administering a compound comprising:
- a) at least one cyclic cell-penetrating peptide (CPP) having a structure of Formula III:
- wherein:
- each of AA1, AA2, AA3, AA4, AAu and AAz is a D or L amino acid;
- m and n are independently selected from a number from 0 to 6;
- and
- wherein the peptide of Formula III comprises at least two arginine and at least two hydrophobic amino acids;
- b) at least one thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the TP has an amino acid sequence that is at least 97% identical to any one of SEQ ID NOS:
- 1-13;
- and
- c) at least one linker (L) that conjugates each CPP and the TP.
Dependencies are inferred from the claim text.