A Review on Advances in Understanding and Therapeutic Strategies for Huntington's Disease

Review Article

Abstract

The trinucleotide repeat expansion of CAG in the huntingtin (HTT) gene is the underlying genetic abnormality responsible for Huntington's Disease (HD), an inherited neurodegenerative disorder characterized by severe cognitive impairment. HD manifests dominantly and is primarily attributed to the toxic gain-of-function effects of the mutant huntingtin protein. Degeneration of medium-spiny neurons within the caudate nucleus and putamen leads to motor, cognitive, and behavioral abnormalities in affected individuals. The estimated incidence of HD ranges from 1/10,000 to 1/20,000 in the Caucasian population, with symptoms typically emerging between the ages of 30 and 50. In addition to cognitive decline, HD can present with psychiatric disturbances and motor symptoms, notably chorea, which progressively affects muscle control and psychomotor skills. Juvenile Huntington's Disease (JHD) may manifest with behavioral issues and learning difficulties before the age of twenty. Given the lack of curative treatments for chorea, management focuses on symptomatic relief through medications targeting dopamine receptors. Multidisciplinary care is essential for optimizing quality of life, with interventions including home remedies and non-pharmacological approaches to address behavioral and psychological symptoms. As the disease progresses, individuals often require increasing levels of care, leading to significant caregiver burden. Tragically, suicide is a common cause of death among individuals with HD. Prognosis in HD is determined by the severity of clinical manifestations and confirmed genetic diagnosis. Effective management strategies aim to alleviate symptoms and enhance overall well-being, underscoring the importance of holistic care approaches in mitigating the impact of this devastating disease