Genomic testing is particularly useful in the diagnosis of familial and early-onset neurodegenerative diseases, for example ataxia, hereditary spastic paraparesis and some forms of dementia and Parkinson’s.
Prior to genomic technologies, testing was done gene by gene. For a condition where there may, for example, be 10 possible genetic causes, this is a time-consuming process which takes its toll on patients and families. Genomic testing enables us to test many genes concurrently and thus speeds up diagnosis in these instances.
Genomic test results can impact whole families. If one person in a family is found to have pathogenic variants, other family members could, too. If such variants are found early, it can enable better clinical management for the whole family and enable individuals to consider their options for the future. For example, identification of the Huntington’s gene mutation in a family with Huntington disease enables the counselling of other family members for risk-management including possible predictive testing and referral to relevant clinical trials.
In some instances, a precise genetic diagnosis means an individual can access gene-directed therapies which have a good chance of benefiting them. In this film, professor Morris talks about the treatment of spinal muscular atrophy (SMA) with Nusinersin. It is hoped that other gene-directed therapies will soon be available.
Clinical trails and drug development
The identification of the genetic cause(s) of a disease makes it easier to develop targeted therapies. For example:
- The identification of mutations in the synuclein gene in Parkinson’s disease, and identifications and mutations in the APP and presenilin genes in Alzheimer’s disease, have allowed for the development of animal models. These animal models have been used to develop antibody-based treatments for these diseases, and those antibody treatments are now in clinical trials. Updates can be found on the Alzoforum website.
- Several years ago, the gene most commonly associated with motor neurone disease – the C9orf72 gene – was identified. A gene therapy trial is now in progress, looking to turn off the abnormal gene and potentially provide a treatment for affected patients (see ‘Genomics in Practice’ example below).
The widespread availability and relative accessibility of genomic testing will result in more trials, more patients being eligible for and recruited to trials, and, as a result, more rapid progress in the area of targeted treatments.
Polygenic risk scores
We know that some people are at higher risk of certain conditions due to a combination of multiple genetic variants – for example Parkinson’s Disease, for which we know of around 90 associated areas of the genome. Estimating this risk to an individual using polygenic risk scores is complex, but it is a focus for research. Genomic technologies make rapid advances in this area probable, but it is likely that clinical geneticists will specialise in this area.