Cargando…

Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’

BACKGROUND: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has be...

Descripción completa

Detalles Bibliográficos
Autores principales: Jennings, Matthew J., Lochmüller, Angela, Atalaia, Antonio, Horvath, Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203235/
https://www.ncbi.nlm.nih.gov/pubmed/32773395
http://dx.doi.org/10.3233/JND-200546
_version_ 1783708128311771136
author Jennings, Matthew J.
Lochmüller, Angela
Atalaia, Antonio
Horvath, Rita
author_facet Jennings, Matthew J.
Lochmüller, Angela
Atalaia, Antonio
Horvath, Rita
author_sort Jennings, Matthew J.
collection PubMed
description BACKGROUND: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking. OBJECTIVE: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. METHODS: We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale. RESULTS: Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH). CONCLUSIONS: The ‘treatable’ variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
format Online
Article
Text
id pubmed-8203235
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher IOS Press
record_format MEDLINE/PubMed
spelling pubmed-82032352021-06-28 Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’ Jennings, Matthew J. Lochmüller, Angela Atalaia, Antonio Horvath, Rita J Neuromuscul Dis Systematic Review BACKGROUND: Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking. OBJECTIVE: We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies. METHODS: We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale. RESULTS: Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH). CONCLUSIONS: The ‘treatable’ variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies. IOS Press 2021-05-13 /pmc/articles/PMC8203235/ /pubmed/32773395 http://dx.doi.org/10.3233/JND-200546 Text en © 2021 – The authors. Published by IOS Press https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Systematic Review
Jennings, Matthew J.
Lochmüller, Angela
Atalaia, Antonio
Horvath, Rita
Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title_full Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title_fullStr Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title_full_unstemmed Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title_short Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a ‘treatabolome’
title_sort targeted therapies for hereditary peripheral neuropathies: systematic review and steps towards a ‘treatabolome’
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203235/
https://www.ncbi.nlm.nih.gov/pubmed/32773395
http://dx.doi.org/10.3233/JND-200546
work_keys_str_mv AT jenningsmatthewj targetedtherapiesforhereditaryperipheralneuropathiessystematicreviewandstepstowardsatreatabolome
AT lochmullerangela targetedtherapiesforhereditaryperipheralneuropathiessystematicreviewandstepstowardsatreatabolome
AT atalaiaantonio targetedtherapiesforhereditaryperipheralneuropathiessystematicreviewandstepstowardsatreatabolome
AT horvathrita targetedtherapiesforhereditaryperipheralneuropathiessystematicreviewandstepstowardsatreatabolome