Medical Genetics seminars

There are no effective disease-modifying therapies for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis or Huntington’s disease. Huntington’s disease (HD) is a devastating autosomal dominantly inherited neurodegenerative disease and the world’s most common genetic dementia. I will present an overview of important approaches in development for targeting mutant HTT DNA and RNA (Tabrizi et al Neuron 2019), the cause of HD pathogenesis, and the translational pathway from bench to clinic for a HTT targeting antisense oligonucleotide (Tabrizi et al New England Journal of Medicine 2019, Tabrizi, Science 2020) which is now in phase 3 studies. In my talk I will also review some of the genetic approaches in development for other CNS diseases. I will talk a bit about my journey as a clinician scientist and share some of my learnings for young scientists on how to survive a career in science.

Lysosomal storage diseases are a group of over 70 inherited metabolic disorders, many of which have a neurodegenerative clinical course. Treatments have been developed for a subset of these disorders and are now in routine clinical use. We have found that some neurological and neurodegenerative diseases share unanticipated links to lysosomal storage diseases providing insights into disease pathogenesis. These links also suggest treatments developed for lysosomal disorders may have unanticipated utility in other rare and common diseases.

Dementia is of global interest because of the rapid increase in both the number of individuals affected and the population at risk. It is essential that the risk factors be carefully delineated for the formulation of preventive strategies. Epigenetics refers to external modifications that turn genes "on" or "off”, and cross-cultural studies of migrant populations provide information on the interplay of environmental factors on genetic predisposition. The Indianapolis-Ibadan Dementia Study compared the prevalence, incidence and risk factors of dementia in African Americans and Yoruba to tease out the role of epigenetics in dementia. The presentation will provide details on biomarkers of dementia, vascular risk factors and the association with apolipoprotein E in the Yoruba. The purpose will be to inspire early career researchers on possibilities and research strategies applicable in African populations

In this talk, Dr Singleton will discuss the progress made so far in understanding the genetic basis of Parkinson’s disease. He will cover the history of discovery from the first identification of disease causing mutations to the state of knowledge in the field today, more that 20 years after that initial discovery. He will then discuss current initiatives and the promise of these for informing the understanding and treatment of Parkinson’s disease. Lastly, Dr Singleton will talk about current gaps in research and knowledge and working together to fill these.