Parkinson’s is a neurodegenerative disease that affects the nervous system, but its signs can also be seen in the blood. As? With a test that measures how damaged the mitochondria of blood cells are, and capable of revealing traces associated with the disease before symptoms appear. There is still no talk of a clinical use test, but measuring mitochondrial damage could one day become a marker of the disease, useful for evaluating the effectiveness of the various therapies under study. To tell all this is a group of international researchers, to which the Italian also contributed Fabio Blandini at the Casimiro Mondino IRCCS National Neurological Institute Foundation of Pavia and today scientific director of the IRCCS Ca’ Granda Ospedale Maggiore Policlinico Foundation of Milan, on pages Of Science Translational Medicine.
The importance of early diagnosis also for neurodegenerative diseases
The hunt for early tests of neurodegenerative diseases is a thriving field of research. The reason is obvious: if we could identify these diseases early, maybe we could hope to intervene before the damage becomes visible in the symptoms, and irreparable. The failure of many studies on therapies against neurodegenerative diseases – not only Parkinson’s but also Alzheimer’s – is in fact largely attributable to too late interventions.
Just a few days ago a team of British researchers suggested that early signs of the disease could be hiding in the eyes, and that it was possible to read them up to seven years earlier with retinal imaging. This time, however, the researchers’ idea was to look in the blood. In fact, blood contains valuable information on the health of our body and, by observing how cell populations and molecular markers vary, it is possible to diagnose various diseases.
Eyes predict Parkinson’s. Seven years before the diagnosis of Valentina Arcovio 22 August 2023
Measure the damage of the mitochondria, in the blood
In this case a possible marker was already there: mitochondrial damage. Mitochondria are small organelles present inside the cell, where they function as small energy plants. They are special not only for this: they contain their own DNA inside. Well, some studies conducted in the past have observed that in people with Parkinson’s the DNA of the mitochondria – for reasons still largely unknown – is damaged. Hence the idea of the researchers to develop a test to measure the integrity of the DNA of the mitochondria (or against its degradation) in blood cells. “We have known of the involvement of mitochondria in the disease since the 1990s, but until now it had not been possible to develop a fast, efficient, reliable and reproducible test to measure it”, comments Blandini. Exactly so far.
A similar test – based on the PCR technique and capable of giving results within 24 hours – actually shows that mitochondrial DNA is more damaged in the blood of Parkinson’s patients than in healthy people. Not only that: he also sees mitochondrial DNA damage in people who carry a mutation associated with the disease, the one in the LRRK2 (leucine-rich repeat kinase 2) gene, but without overt disease. This suggests that it is possible to identify signs before symptoms appear, even if – the researchers point out – it is not said that people with the mutation will then develop clinical signs of the disease. “Tests have also been conducted on patients with Alzheimer’s, demonstrating that in these it is not possible to observe this mitochondrial damage, which is therefore not merely linked to neurodegeneration”, continues the expert: “At the same time it has been observed that there is no correlation between the amount of damage observed and the severity of symptoms: it is as if this test photographs an intrinsic condition of people who have the disease”. Or that they could develop it.
Parkinson, so physical exercise could slow down Tiziana Moriconi’s disease 14 July 2023
Early diagnosis and study of new drugs
The potential therefore of this examination, or of similar tests, is that of being able to use them one day for early diagnoses, potentially also increasing the effectiveness of therapies, he explained Laura Sanders of Duke University School of Medicine, who led the study. At the moment, however, we are still far from all this. “We still don’t have a perfect marker, capable of clearly discriminating patients from healthy subjects, not even this test allows it – continues Blandini – Larger studies in the future could help to better define the diagnostic and predictive character of a similar test” .
The possibility of using a similar test in trials, as a useful marker to stratify patients, appears closer, explain the authors. “As we recall in the paper, each patient is different from the other and continuing to treat all Parkinson’s patients in the same way within the trials puts at risk the possibility of finding a drug”, concludes Blandini. In fact, the researchers showed, in experiments on animals and on cultured cells, that the test is capable of observing a reduction of mitochondrial damage in the presence of an LRRK2 inhibitor. Here then, Sanders continues: “a clear diagnosis would precisely identify patients who could participate in drug studies, leading to the development of better treatments and potentially even cures”.
But first, the authors conclude, it will be necessary to test its reliability on larger numbers (there are only a hundred samples analyzed for now) and to better understand how mitochondrial damage changes over time.