Huntington’s disease (HD) is a rare and complex neurodegenerative disorder that causes progressive motor, cognitive, and psychiatric symptoms.

It is caused by a mutation in the Huntingtin gene, which leads to the production of a mutant Huntingtin protein that accumulates in the brain and damages neurons over time. There is currently no cure for HD, and available treatments only manage symptoms. However, early detection of HD can help patients and families prepare for the future and potentially participate in clinical trials for new therapies.

That is why the development of a blood test to forecast the onset of HD is a significant breakthrough.

What is the blood test for HD?

The blood test for HD is a pioneering diagnostic tool that draws on the discovery of specific biomarkers that can suggest the presence of the Huntingtin protein in the blood. In 2014, researchers at University College London led by Dr.

Sarah Tabrizi identified a set of five genes whose expression levels were associated with the age of onset of HD, as well as the progression of the disease. They found that these genes were more active in people with HD than in healthy individuals. Moreover, the blood levels of these genes were correlated with each other and appeared to reflect the amount of mutant Huntingtin protein in the brain.

Based on these findings, the researchers developed a blood test that measures the levels of the five genes and generates a score that predicts the likelihood of developing HD.

How does the blood test work?

The blood test for HD works by analyzing the RNA molecules in a person’s blood, which reflect the expression levels of the five genes associated with HD.

The test uses a technique called quantitative PCR, which amplifies the RNA molecules and allows their levels to be measured in relative units. The results are then compared to a reference population of unaffected individuals and translated into a score that reflects the estimated years until the onset of HD.

The blood test is not a definitive diagnosis of HD, but rather a screening tool that can indicate the need for further testing or monitoring. The test is also not suitable for people who have already been diagnosed with HD, as their gene expression patterns may be different from those who are asymptomatic.

What are the benefits of the blood test?

The blood test for HD has several potential benefits for patients, families, and researchers.

Firstly, the test can provide early warning signs of HD before the onset of symptoms, allowing for more proactive management of the disease and preparation for the future. Secondly, the test can identify individuals who are at risk of developing HD but who have not yet been diagnosed, enabling them to seek the appropriate medical advice and support.

Thirdly, the test can facilitate clinical trials of new treatments for HD by identifying suitable candidates at an early stage. Finally, the test can contribute to the understanding of HD by revealing the underlying biological processes that lead to the disease and potential targets for therapy.

Is the blood test accurate?

The blood test for HD has been shown to be highly accurate in predicting the onset of HD in asymptomatic individuals.

In a large validation study involving over 1000 participants, the test correctly predicted the age of onset of HD with an average error of only 0.6 years. The test also had a specificity of 91%, meaning that it correctly identified unaffected individuals, and a sensitivity of 87%, meaning that it correctly identified individuals who went on to develop HD.

These results demonstrate the reliability and reproducibility of the blood test across different populations and laboratories. However, further studies are needed to assess the performance of the blood test in clinical settings and to compare it to other diagnostic tools for HD.

What are the limitations of the blood test?

The blood test for HD is a valuable tool, but it has some limitations that need to be taken into account. Firstly, the test is not a definitive diagnosis of HD, as it only provides a probability estimate based on the expression levels of the five genes.

Therefore, a positive result does not mean that an individual will definitely develop HD, and a negative result does not rule out the possibility of developing HD. Secondly, the test is only useful for asymptomatic individuals who have not yet been diagnosed with HD.

It is not suitable for people who have already been diagnosed with HD, as their gene expression patterns may differ from those of pre-symptomatic individuals. Thirdly, the test is not widely available or affordable, and it requires specialized equipment and expertise to perform. Therefore, its use is currently limited to research centers and specialized clinics.

What is the future of the blood test?

The blood test for HD holds great promise for the future of HD diagnosis and treatment.

It represents a significant step forward in our understanding of the molecular mechanisms underlying HD and provides a non-invasive and accessible tool for early detection and monitoring. Moreover, the blood test has the potential to transform clinical trials of new therapies for HD by providing a more accurate and timely assessment of treatment efficacy.

However, further research is needed to optimize the test’s performance, validate its use in clinical settings, and expand its availability and affordability. Additionally, the blood test may be extended to predict the onset of other neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease, which share common features with HD.

Conclusion

The development of the blood test for HD represents a significant milestone in the field of neurodegenerative disorders and highlights the potential of biomarker-based diagnostics. The test is based on the pioneering work of Dr.

Sarah Tabrizi and her team at University College London and provides a non-invasive and accurate tool for predicting the onset of HD. The test has several potential benefits for patients, families, and researchers, but also has some limitations that need to be taken into account.

The future of the blood test depends on further optimization, validation, and expansion to other disorders, but its potential impact on HD diagnosis and treatment is significant.