Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

Amber L Southwell; Niels H Skotte; C Frank Bennett; Michael R Hayden

doi:10.1016/j.molmed.2012.09.001

Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

Amber L Southwell, Niels H Skotte, C Frank Bennett, Michael R Hayden

89 Citationer (Scopus)

Abstract

The rising median age of our population and the age-dependent risk of neurodegeneration translate to exponentially increasing numbers of afflicted individuals in the coming years. Although symptomatic treatments are available for some neurodegenerative diseases, most are only moderately efficacious and are often associated with significant side effects. The development of small molecule, disease-modifying drugs has been hindered by complex pathogenesis and a failure to clearly define the rate-limiting steps in disease progression. An alternative approach is to directly target the mutant gene product or a defined causative protein. Antisense oligonucleotides (ASOs) - with their diverse functionality, high target specificity, and relative ease of central nervous system (CNS) delivery - are uniquely positioned as potential therapies for neurological diseases. Here we review the development of ASOs for the treatment of inherited neurodegenerative diseases.

Originalsprog	Engelsk
Tidsskrift	Trends in Molecular Medicine
Vol/bind	18
Udgave nummer	11
Sider (fra-til)	634-43
Antal sider	10
ISSN	1471-4914
DOI	https://doi.org/10.1016/j.molmed.2012.09.001
Status	Udgivet - nov. 2012
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.molmed.2012.09.001

Citationsformater

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title = "Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases",

abstract = "The rising median age of our population and the age-dependent risk of neurodegeneration translate to exponentially increasing numbers of afflicted individuals in the coming years. Although symptomatic treatments are available for some neurodegenerative diseases, most are only moderately efficacious and are often associated with significant side effects. The development of small molecule, disease-modifying drugs has been hindered by complex pathogenesis and a failure to clearly define the rate-limiting steps in disease progression. An alternative approach is to directly target the mutant gene product or a defined causative protein. Antisense oligonucleotides (ASOs) - with their diverse functionality, high target specificity, and relative ease of central nervous system (CNS) delivery - are uniquely positioned as potential therapies for neurological diseases. Here we review the development of ASOs for the treatment of inherited neurodegenerative diseases.",

keywords = "Animals, Clinical Trials as Topic, Gene Transfer Techniques, Genetic Therapy, Heredodegenerative Disorders, Nervous System, Humans, Oligonucleotides, Antisense, RNA Interference",

author = "Southwell, {Amber L} and Skotte, {Niels H} and Bennett, {C Frank} and Hayden, {Michael R}",

year = "2012",

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doi = "10.1016/j.molmed.2012.09.001",

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T1 - Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

AU - Southwell, Amber L

AU - Skotte, Niels H

AU - Bennett, C Frank

AU - Hayden, Michael R

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N2 - The rising median age of our population and the age-dependent risk of neurodegeneration translate to exponentially increasing numbers of afflicted individuals in the coming years. Although symptomatic treatments are available for some neurodegenerative diseases, most are only moderately efficacious and are often associated with significant side effects. The development of small molecule, disease-modifying drugs has been hindered by complex pathogenesis and a failure to clearly define the rate-limiting steps in disease progression. An alternative approach is to directly target the mutant gene product or a defined causative protein. Antisense oligonucleotides (ASOs) - with their diverse functionality, high target specificity, and relative ease of central nervous system (CNS) delivery - are uniquely positioned as potential therapies for neurological diseases. Here we review the development of ASOs for the treatment of inherited neurodegenerative diseases.

AB - The rising median age of our population and the age-dependent risk of neurodegeneration translate to exponentially increasing numbers of afflicted individuals in the coming years. Although symptomatic treatments are available for some neurodegenerative diseases, most are only moderately efficacious and are often associated with significant side effects. The development of small molecule, disease-modifying drugs has been hindered by complex pathogenesis and a failure to clearly define the rate-limiting steps in disease progression. An alternative approach is to directly target the mutant gene product or a defined causative protein. Antisense oligonucleotides (ASOs) - with their diverse functionality, high target specificity, and relative ease of central nervous system (CNS) delivery - are uniquely positioned as potential therapies for neurological diseases. Here we review the development of ASOs for the treatment of inherited neurodegenerative diseases.

KW - Animals

KW - Clinical Trials as Topic

KW - Gene Transfer Techniques

KW - Genetic Therapy

KW - Heredodegenerative Disorders, Nervous System

KW - Humans

KW - Oligonucleotides, Antisense

KW - RNA Interference

U2 - 10.1016/j.molmed.2012.09.001

DO - 10.1016/j.molmed.2012.09.001

M3 - Journal article

C2 - 23026741

SN - 1471-4914

VL - 18

SP - 634

EP - 643

JO - Trends in Molecular Medicine

JF - Trends in Molecular Medicine

IS - 11

ER -

Antisense oligonucleotide therapeutics for inherited neurodegenerative diseases

Abstract

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