Abstract
Among hereditary diseases, the group of motor neuron diseases (MNDs) includes some of the most devastating and rapidly progressive lethal conditions. Although degeneration of motor neurons is common to all of them, the phenotypic spectrum of MNDs is relatively broad and ranges from perinatal conditions like spinal muscular atrophy (SMA) to adult-onset diseases such as amyotrophic lateral sclerosis (ALS). While the understanding of the pathology of the diseases is constantly growing, the development of therapeutic approaches lags behind. In fact, there is no approved therapy for MNDs available at the moment.
Recent findings demonstrated the existence of some patterns that are shared by several MNDs such as transcriptional dysregulation. In addition, conditions like SMA or certain types of Charcot-Marie-Tooth disease provide some defined targets which may be amenable to therapeutic approaches. Consequently, counteracting this dysregulation may be a valuable therapeutic option and ameliorate disease progression in MND patients. The feasibility of such an approach has been proven during the past years by the epigenetic treatment of various neoplastic entities with histone deacetylase inhibitors (HDACi). On these grounds, also epigenetic therapy of MNDs has become a promising option. So far, several HDACi have been tested in vitro and in animal models and some proceeded further and were evaluated in clinical trials. This review will summarize the advances of HDACi in MNDs and will give a perspective where the road will lead us.
Keywords: Amyotrophic lateral sclerosis, spinal muscular atrophy, spinal and bulbar muscular atrophy, HSP1, HDAC inhibitor, valproic acid, SAHA, trichostatin A.
Current Pharmaceutical Design
Title:Histone Acetylation as a Potential Therapeutic Target in Motor Neuron Degenerative Diseases
Volume: 19 Issue: 28
Author(s): Lutz Garbes, Markus Riessland and Brunhilde Wirth
Affiliation:
Keywords: Amyotrophic lateral sclerosis, spinal muscular atrophy, spinal and bulbar muscular atrophy, HSP1, HDAC inhibitor, valproic acid, SAHA, trichostatin A.
Abstract: Among hereditary diseases, the group of motor neuron diseases (MNDs) includes some of the most devastating and rapidly progressive lethal conditions. Although degeneration of motor neurons is common to all of them, the phenotypic spectrum of MNDs is relatively broad and ranges from perinatal conditions like spinal muscular atrophy (SMA) to adult-onset diseases such as amyotrophic lateral sclerosis (ALS). While the understanding of the pathology of the diseases is constantly growing, the development of therapeutic approaches lags behind. In fact, there is no approved therapy for MNDs available at the moment.
Recent findings demonstrated the existence of some patterns that are shared by several MNDs such as transcriptional dysregulation. In addition, conditions like SMA or certain types of Charcot-Marie-Tooth disease provide some defined targets which may be amenable to therapeutic approaches. Consequently, counteracting this dysregulation may be a valuable therapeutic option and ameliorate disease progression in MND patients. The feasibility of such an approach has been proven during the past years by the epigenetic treatment of various neoplastic entities with histone deacetylase inhibitors (HDACi). On these grounds, also epigenetic therapy of MNDs has become a promising option. So far, several HDACi have been tested in vitro and in animal models and some proceeded further and were evaluated in clinical trials. This review will summarize the advances of HDACi in MNDs and will give a perspective where the road will lead us.
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Cite this article as:
Garbes Lutz, Riessland Markus and Wirth Brunhilde, Histone Acetylation as a Potential Therapeutic Target in Motor Neuron Degenerative Diseases, Current Pharmaceutical Design 2013; 19 (28) . https://dx.doi.org/10.2174/13816128113199990356
DOI https://dx.doi.org/10.2174/13816128113199990356 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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