Methods and compositions for inhibiting PMP22 expression
Inventors
Hung, Gene • Kordasiewicz, Holly • Zhao, Hien Thuy • Swayze, Eric E.
Assignees
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Publication Number
US-12529055-B2
Publication Date
2026-01-20
Expiration Date
Abstract
The present embodiments provide methods, compounds, and compositions useful for inhibiting PMP22 expression and for treating, preventing, or ameliorating a disease associated with PMP22.
Core Innovation
The invention provides a method of treating an individual exhibiting a symptom of Charcot-Marie-Tooth Disease and having a duplication of the peripheral myelin protein 22 (PMP22) gene. The method includes determining whether the individual has a slowed motor nerve conduction velocity (MNCV), a reduced compound muscle action potential (CMAP), or a combination thereof, and administering a pharmaceutical composition when these criteria are present.
The pharmaceutical composition includes an antisense compound and a pharmaceutically acceptable diluent. The antisense compound comprises an antisense oligonucleotide that includes at least 12 contiguous nucleobases complementary to a target region of the PMP22 transcript and is used to inhibit PMP22 expression in the context of PMP22 gene duplication-associated disease.
The embodiments further specify antisense oligonucleotides with at least 80% complementary nucleobase sequence to the PMP22 transcript target region. The oligonucleotide may include modified internucleoside linkages, including phosphorothioate internucleoside linkages, and may be a single-stranded antisense compound. Formulation details include phosphate-buffered saline (PBS) as a pharmaceutically acceptable diluent.
Claims Coverage
The document provides one independent claim and dependent claim refinements. The independent claim covers a treatment method for individuals with Charcot-Marie-Tooth Disease, PMP22 gene duplication, and slowed MNCV and/or reduced CMAP, using an antisense oligonucleotide with at least 12 contiguous complementary nucleobases to a PMP22 transcript target region.
Treating PMP22 duplication-associated Charcot-Marie-Tooth based on MNCV/CMAP determination
A method of treating an individual exhibiting a symptom of Charcot-Marie-Tooth Disease and having a duplication of the peripheral myelin protein 22 (PMP22) gene by determining whether the individual has a slowed motor nerve conduction velocity (MNCV), a reduced compound muscle action potential (CMAP), or a combination thereof, and administering a pharmaceutical composition when slowed MNCV, reduced CMAP, or a combination is present.
Antisense composition with an oligonucleotide of at least 12 contiguous complementary nucleobases to the PMP22 transcript
A pharmaceutical composition comprising an antisense compound and a pharmaceutically acceptable diluent, where the antisense compound comprises an antisense oligonucleotide that comprises at least 12 contiguous nucleobases complementary to a target region of the PMP22 transcript.
Quantitative complementarity of at least 80% to the PMP22 transcript target region
An antisense oligonucleotide whose nucleobase sequence is at least 80% complementary to the target region of the PMP22 transcript.
Modified internucleoside linkage in the antisense oligonucleotide
The antisense oligonucleotide includes at least one modified internucleoside linkage.
Phosphorothioate internucleoside linkage
The at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.
Single-stranded antisense compound
The antisense compound is a single-stranded antisense compound.
Phosphate-buffered saline (PBS) diluent
The pharmaceutically acceptable diluent is phosphate-buffered saline (PBS).
Overall, the claim coverage focuses on treating PMP22 duplication-associated Charcot-Marie-Tooth Disease based on slowed MNCV and/or reduced CMAP, using an antisense pharmaceutical composition with an antisense oligonucleotide containing at least 12 contiguous nucleobases complementary to a target region of the PMP22 transcript, with further refinements including at least 80% complementarity, modified internucleoside linkages, single-stranded format, and PBS diluent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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