Purpose Of Review: Huntington's disease is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide expansion in the HTT gene, and current therapies focus on symptomatic treatment. This review explores therapeutic approaches that directly target the pathogenic mutation, disrupt HTT mRNA or its translation.
Recent Findings: Zinc-finger transcription repressors and CRISPR-Cas9 therapies target HTT DNA, thereby preventing all downstream pathogenic mechanisms. These therapies, together with RNA interference (RNAi), require intraparenchymal delivery to the brain in viral vectors, with only a single delivery potentially required, though they may carry the risk of irreversible side-effects.Along with RNAi, antisense oligonucleotides (ASOs) target mRNA, but are delivered periodically and intrathecally. ASOs have safely decreased mutant huntingtin protein (mHTT) levels in the central nervous system of patients, and a phase 3 clinical trial is currently underway.Finally, orally available small molecules, acting on splicing or posttranslational modification, have recently been shown to decrease mHTT in animal models.
Summary: Huntingtin-lowering approaches act upstream of pathogenic mechanisms and therefore have a high a priori likelihood of modifying disease course. ASOs are already in late-stage clinical development, whereas other strategies are progressing rapidly toward human studies.
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http://dx.doi.org/10.1097/WCO.0000000000000835 | DOI Listing |
Background: There are no disease modifying therapies for Huntington's disease (HD), a rare but fatal genetic neurodegenerative condition. To develop and test new management strategies, a better understanding of the mechanisms underlying HD progression is needed. Aberrant changes in thalamo-cortical and striato-cerebellar circuitry have been observed in asymptomatic HD, along with transient enlargement of the dentate nucleus.
View Article and Find Full Text PDFMethods Cell Biol
January 2025
State University of Minas Gerais, Department of Biomedical Sciences and Health, Passos, MG, Brazil. Electronic address:
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by a repeat of the cytosine-adenine-guanine trinucleotide (CAG) in the huntingtin gene (HTT). This results in the translation of a mutant huntingtin (mHTT) protein with an abnormally long polyglutamine (polyQ) repeat. The pathology of HD leads to neuronal cell loss, motor abnormalities, and dementia.
View Article and Find Full Text PDFJ Biomed Inform
January 2025
Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, 02115, MA, USA; VA Boston Healthcare System, 150 S Huntington Ave, Boston, 02130, MA, USA. Electronic address:
Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. To address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features.
View Article and Find Full Text PDFMolecules
January 2025
Chair and Department of Biochemistry and Pharmacogenomics, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.
Vitamin B (thiamine) plays an important role in human metabolism. It is essential for the proper growth and development of the body and has a positive effect on the functioning of the digestive, cardiovascular, and nervous systems. Additionally, it stimulates the brain and improves the psycho-emotional state.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego 5, 02-004 Warsaw, Poland.
Diabetes mellitus (DM) and neurodegenerative diseases/disturbances are worldwide health problems. The most common chronic conditions diagnosed in persons 60 years and older are type 2 diabetes mellitus (T2DM) and cognitive impairment. It was found that diabetes mellitus is a major risk for cognitive decline, dementia, Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders.
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