ABC: A Duty to Balance Conflicting Interests
Robert Wheeler in Clinical Law for Clinical Practice, 2020
This chapter presents a case study of a lady, whose father, killed her mother, leading to his detention in a psychiatric facility. His clinicians tested him for Huntington's disease, which proved positive. He had capacity, and agreed to the testing only on the basis that his results were not shared with his family. In the meantime, the lady fell pregnant. Her father's doctors knew about the pregnancy and wanted to disclose his diagnosis to his daughter; from the time of his diagnosis there would have been a window of 2 months during which termination of her pregnancy was feasible. The claimant told the court that the clinicians had a ‘duty to balance the Claimant's interest in being informed of her risk of a genetic disorder against her father's interest in having the confidentiality of that diagnosis preserved’. The judge reflected that this duty would rarely act as foundation for litigation.
Genetics, ethics and society
Peter S. Harper in The Evolution of Medical Genetics, 2019
Both practice and research in medical genetics encounter numerous ethical issues, something that is inevitable given the many personal and sensitive aspects involved. Since medical genetics turned its back on eugenics after World War II, beginning with the example of Penrose and the Galton Laboratory, those working in the field have mostly been highly sensitive to these ethical aspects and have led the way in identifying and analysing them, and later in alerting those in other countries and other fields of medicine to their existence. Prenatal diagnosis and issues surrounding termination of pregnancy arose in the 1970s, but the most difficult have been those involving molecular genetic testing from the 1980s on, especially prediction of late-onset genetic disorders such as Huntington's disease. Extensive studies of these problems led to increasing involvement and collaboration of those in the social sciences and humanities, and to the creation of formal bodies such as the Human Genetics Commission and Nuffield Council on Bioethics, with numerous valuable reports influencing both government and professionals, in Britain and abroad. A related important development has been the growth of numerous lay societies for genetic disorders, often working closely with medical geneticists.
Central nervous system: Adult-onset and psychiatric disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
The central nervous system disorders of adult life considered here fall into two main groups: the neurodegenerative disorders and dementias, and another group, of the psychiatric disorders of adult life, that has intriguingly close aetiological links with neurodevelopmental disorders although these links remain ill defined. Huntington's disease, due to an expanded and unstable trinucleotide repeat, represents one of the most difficult genetic counselling problems among the Mendelian disorders of adult life. Parkinsonian features may occur in more general brain degenerations, such as frontotemporal and Lewy body dementias, prion disease, spinocerebellar ataxias, Wilson disease and others, including non-genetic disorders and weakly genetic disorders. Alzheimer’s disease is the most common dementia of old age, and increased survival makes it a major problem for society as well as for individual families. Late-onset ataxia accompanied by upper motor neurone signs is a heterogenous group and has been found to result from trinucleotide repeat expansions in specific genes.
Huntington's disease is a multi-system disorder
Published in Rare Diseases, 2015
Huntington's disease (HD) is one of the most common non-curable rare diseases and is characterized by choreic movements, psychiatric symptoms, and slowly progressive dementia. HD is inherited as an autosomal dominant disorder with complete penetrance. Although brain pathology has become a hallmark of HD, there is a critical mass of new studies suggesting peripheral tissue pathology as an important factor in disease progression. In particular, recently published studies about skeletal muscle malfunction and HD-related cardiomyopathy in HD mouse models strongly suggest their important roles, leading to upcoming preclinical and clinical trials. One might conclude that therapeutic approaches in HD should not be restricted only to the brain pathology but instead major efforts should also be made to understand the cross-talk between diseased tissues like the CNS-Heart or CNS-skeletal muscle axes.
Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity
Published in Rare Diseases, 2016
Helen Budworth, Cynthia T. McMurray
Huntington's Disease is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. Whether somatic expansion contributed to toxicity was unknown. From extensive work from multiple laboratories, it has been made clear that toxicity depended on length of the inherited allele, but whether preventing or delaying somatic repeat expansion in vivo would be beneficial was unknown, since the inherited disease allele was still expressed. In Budworth et al., we provided definitive evidence that suppressing the somatic expansion in mice substantially delays disease onset in littermates that inherit the same disease-length allele. This key discovery opens the door for therapeutic approaches targeted at stopping or shortening the CAG tract during life. The analysis was difficult and, at times, non-standard. Here, we take the opportunity to discuss the challenges, the analytical solutions, and to address some controversial issues with respect to expansion biology.
The calpain-suppressing effects of olesoxime in Huntington's disease
Published in Rare Diseases, 2016
Jonasz J. Weber, Midea M. Ortiz Rios, Olaf Riess, Laura E. Clemens, Huu P. Nguyen
Olesoxime, a small molecule drug candidate, has recently attracted attention due to its significant beneficial effects in models of several neurodegenerative disorders including Huntington's disease. Olesoxime's neuroprotective effects have been assumed to be conveyed through a direct, positive influence on mitochondrial function. In a long-term treatment study in BACHD rats, the latest rat model of Huntington's disease, olesoxime revealed a positive influence on mitochondrial function and improved specific behavioral and neuropathological phenotypes. Moreover, a novel target of the compound was discovered, as olesoxime was found to suppress the activation of the calpain proteolytic system, a major contributor to the cleavage of the disease-causing mutant huntingtin protein into toxic fragments, and key player in degenerative processes in general. Results from a second model of Huntington's disease, the HdhQ111 knock-in mouse, confirm olesoxime's calpain-suppressing effects and support the therapeutic value of olesoxime for Huntington's disease and other disorders involving calpain overactivation.
Related Knowledge Centers
- Chorea
- Genetic Testing
- Neurodegenerative Disease
- Genetic Disorder
- Recessive
- Genetic Anticipation
- Hereditary Disease Foundation