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Recent advances in understanding hereditary spastic paraplegias and emerging therapies
Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops o...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Faculty Opinions Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009193/ https://www.ncbi.nlm.nih.gov/pubmed/33817696 http://dx.doi.org/10.12703/r/10-27 |
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author | Lallemant-Dudek, Pauline Darios, Frederic Durr, Alexandra |
author_facet | Lallemant-Dudek, Pauline Darios, Frederic Durr, Alexandra |
author_sort | Lallemant-Dudek, Pauline |
collection | PubMed |
description | Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7, which is responsible for HSP or cerebellar ataxia or both. There are no specific therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific therapy has been developed for HSP, but emerging therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients. |
format | Online Article Text |
id | pubmed-8009193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Faculty Opinions Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-80091932021-04-01 Recent advances in understanding hereditary spastic paraplegias and emerging therapies Lallemant-Dudek, Pauline Darios, Frederic Durr, Alexandra Fac Rev Review Article Hereditary spastic paraplegias (HSPs) are a group of rare, inherited, neurological diseases characterized by broad clinical and genetic heterogeneity. Lower-limb spasticity with first motoneuron involvement is the core symptom of all HSPs. As spasticity is a syndrome and not a disease, it develops on top of other neurological signs (ataxia, dystonia, and parkinsonism). Indeed, the definition of genes responsible for HSPs goes beyond the 79 identified SPG genes. In order to avoid making a catalog of the different genes involved in HSP in any way, we have chosen to focus on the HSP with cerebellar ataxias since this is a frequent association described for several genes. This overlap leads to an intermediary group of spastic ataxias which is actively genetically and clinically studied. The most striking example is SPG7, which is responsible for HSP or cerebellar ataxia or both. There are no specific therapies against HSPs, and there is a dearth of randomized trials in patients with HSP, especially on spasticity when it likely results from other mechanisms. Thus far, no gene-specific therapy has been developed for HSP, but emerging therapies in animal models and neurons derived from induced pluripotent stem cells are potential treatments for patients. Faculty Opinions Ltd 2021-03-10 /pmc/articles/PMC8009193/ /pubmed/33817696 http://dx.doi.org/10.12703/r/10-27 Text en Copyright: © 2021 Durr A et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Lallemant-Dudek, Pauline Darios, Frederic Durr, Alexandra Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title | Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title_full | Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title_fullStr | Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title_full_unstemmed | Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title_short | Recent advances in understanding hereditary spastic paraplegias and emerging therapies |
title_sort | recent advances in understanding hereditary spastic paraplegias and emerging therapies |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009193/ https://www.ncbi.nlm.nih.gov/pubmed/33817696 http://dx.doi.org/10.12703/r/10-27 |
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