Huntington’s Disease: Clinical Complexities and Therapeutic Strategies

Abstract

Named after physician George Huntington, Huntington's disease (HD) is an adult onset, rare, progressive, fatal, neurodegenerative autosomal dominant disorder, clinically characterized by abnormal movements, dementia, and psychiatric syndromes. The mechanisms by which neuronal degeneration and cell death are being generated in HD may include excitotoxicity, energy deficit, oxidative stress, inflammatory processes, and protein aggregation. Genetically, HD is caused by expanded CAG repeat in the Huntington gene which encodes an abnormally long polyglutamine repeat in the Huntington protein. HD share several of feature of other neurodegenerative disorders like delayed onset, selective neuronal vulnerability, abnormal protein aggregation and processing and cellular toxic effects involving both cell autonomous and cell cell interaction. In the brain, the basal ganglia (caudate and the putamen) is highly affected which organize muscle-driven movements of the body or motor movement. The disease is characterized by a primary progressive loss of medium spiny projection neurons within the basal ganglia. Unfortunately, there is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blockingor depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring fulltime care, and finally death. The most common cause of death is pneumonia, followed by suicide.