Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone deacetylases (HDACs)--enzymes that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Pharmacological manipulations using small-molecule HDAC inhibitors--which may restore transcriptional balance to neurons, modulate cytoskeletal function, affect immune responses and enhance protein degradation pathways--have been beneficial in various experimental models of brain diseases. Although mounting data predict a therapeutic benefit for HDAC-based therapy, drug discovery and development of clinical candidates face significant challenges. Here, we summarize the current state of development of HDAC therapeutics and their application for the treatment of human brain disorders such as Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple sclerosis.
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PMID:Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. 1882 28

The approval of suberoylanilide hydroxamic acid by the FDA for the treatment of cutaneous T-cell lymphoma in October, 2006 sparked a dramatic increase in the development of inhibitors for the class of enzymes known as the histone deacetylases (HDACs). In recent years, a large number of combination therapies involving histone deacetylase inhibitors (HDACIs) have been developed for the treatment of a variety of malignancies and neurodegenerative disorders. Promising evidence has been reported for the treatment of pancreatic cancer, prostate cancer, and leukemia as well as a number of other previously difficult to treat cancers. Drug combination approaches have also shown promise for the treatment of mood disorders including bipolar disorder and depression. In addition to these drug combination approaches, HDACIs alone have demonstrated effectiveness in the treatment of Parkinson's disease, Alzheimer's disease, Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease, multiple sclerosis, anxiety, and schizophrenia. Adverse inflammatory affects observed with traumatic brain injury and arthritis have also been alleviated by treatment with certain HDACIs. Based on the diverse utility and wide range of mechanistic actions observed with this class of drugs, the future development of better drug combination therapies and more selective HDACIs is warranted.
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PMID:Creating zinc monkey wrenches in the treatment of epigenetic disorders. 1954 31

The pathophysiological mechanisms underlying childhood neurological disorders have remained obscure due to a lack of suitable disease models reflecting human pathogenesis. Using induced pluripotent stem cell (iPSC) technology, various neurological disorders can now be extensively modeled. Specifically, iPSC technology has aided the study and treatment of early-onset pediatric neurodegenerative diseases such as Rett syndrome, Down syndrome, Angelman syndrome. Prader-Willi syndrome, Friedreich's ataxia, spinal muscular atrophy (SMA), fragile X syndrome, X-linked adrenoleukodystrophy (ALD), and SCN1A gene-related epilepsies. In this paper, we provide an overview of various gene delivery systems for generating iPSCs, the current state of modeling early-onset neurological disorders and the ultimate application of these in vitro models in cell therapy through the correction of disease-specific mutations.
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PMID:Induced pluripotent stem cells for modeling of pediatric neurological disorders. 2483 56

Epigenetics is a growing field of knowledge that is changing our understanding of pathologic processes. For many cerebellar disorders, recent discoveries of epigenetic mechanisms help us to understand their pathophysiology. In this chapter, a short explanation of each epigenetic mechanism (including methylation, histone modification, and miRNA) is followed by references to those cerebellar disorders in which relevant epigenetic advances have been made. The importance of normal timing and distribution of methylation during neurodevelopment is explained. Abnormal methylation and altered gene expression in the developing cerebellum have been related to neurodevelopmental disorders such as autism, Rett syndrome, and fragile X syndrome. DNA packaging by histones is another important epigenetic mechanism in cerebellar functioning. Current knowledge of histone abnormalities in cerebellar diseases such as Friedreich ataxia and spinocerebellar ataxias is reviewed, including implications for new therapeutic approaches to these degenerative diseases. Finally, micro RNAs, the third mechanism to modulate DNA expression, and their role in normal cerebellar development and disease are described. Understanding how genetic and epigenetic mechanisms interact not only in normal cerebellar development but also in disease is a great challenge. However, such understanding will lead to promising new therapeutic possibilities as is already occurring in other areas of medicine.
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PMID:Epigenetic cerebellar diseases. 2989 Oct 61