Application of antisense conjugates for the treatment of myotonic dystrophy type 1
Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules a...
| Main Authors: | , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
MDPI
2023
|
| _version_ | 1797110375371505664 |
|---|---|
| author | Stoodley, J Vallejo-Bedia, F Seone-Miraz, D Debasa-Mouce, M Wood, MJA Varela, MA |
| author_facet | Stoodley, J Vallejo-Bedia, F Seone-Miraz, D Debasa-Mouce, M Wood, MJA Varela, MA |
| author_sort | Stoodley, J |
| collection | OXFORD |
| description | Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising. |
| first_indexed | 2024-03-07T07:54:07Z |
| format | Journal article |
| id | oxford-uuid:282e4e39-4221-4dc9-98ad-8fe7af0e7c39 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:54:07Z |
| publishDate | 2023 |
| publisher | MDPI |
| record_format | dspace |
| spelling | oxford-uuid:282e4e39-4221-4dc9-98ad-8fe7af0e7c392023-08-11T11:36:12ZApplication of antisense conjugates for the treatment of myotonic dystrophy type 1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:282e4e39-4221-4dc9-98ad-8fe7af0e7c39EnglishSymplectic ElementsMDPI2023Stoodley, JVallejo-Bedia, FSeone-Miraz, DDebasa-Mouce, MWood, MJAVarela, MAMyotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising. |
| spellingShingle | Stoodley, J Vallejo-Bedia, F Seone-Miraz, D Debasa-Mouce, M Wood, MJA Varela, MA Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title | Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title_full | Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title_fullStr | Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title_full_unstemmed | Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title_short | Application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| title_sort | application of antisense conjugates for the treatment of myotonic dystrophy type 1 |
| work_keys_str_mv | AT stoodleyj applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 AT vallejobediaf applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 AT seonemirazd applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 AT debasamoucem applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 AT woodmja applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 AT varelama applicationofantisenseconjugatesforthetreatmentofmyotonicdystrophytype1 |