Thursday April 13, 2023
“Groundbreaking”, “new era” and great hope for patients and treating physicians: A new method makes it possible to detect the onset of Parkinson’s disease even before the brain is damaged. It could be a crucial step for the development of therapies.
A protein in the cerebrospinal fluid could make Parkinson’s detectable long before the disease breaks out and even before brain damage occurs. An international research team writes in the journal that the test can significantly improve the development of therapies “The Lancet Neurology”.
In a comment, Daniela Berg and Christine Klein from the Schleswig-Holstein University Hospital call the method for detecting the misfolded protein alpha-synuclein a “game changer” for the diagnosis, research and treatment of Parkinson’s disease. The President of the German Society of Neurology (DGN), Lars Timmermann, expects the findings to have an impact on new therapies over the next few years.
300,000 sick people in Germany
Magnetic resonance imaging (MRI) of Parkinson’s disease, a degenerative disorder of the central nervous system.
(Foto: picture alliance / BSIP)
Magnetic resonance imaging (MRI) of Parkinson’s disease, a degenerative disorder of the central nervous system.
(Foto: picture alliance / BSIP)
According to estimates, around 300,000 people live with Parkinson’s disease in Germany – making it the second most common neurodegenerative disease after Alzheimer’s dementia. The treatment of Parkinson’s has so far been subject to a major dilemma: if the disease is diagnosed on the basis of typical movement disorders such as tremors or muscle stiffness, the substantia nigra brain area, which is crucial for the coordination of movements, has been damaged for years.
Genetic risk factors such as the gene variants GBA and LRRK2 increase the risk of disease, as do other factors such as age, exposure to pesticides or brain injuries. The misfolded protein alpha-synuclein, which occurs in nerve cells and can form clumps and deposits in the midbrain, plays a key role. The deposits called Lewy bodies are considered the main feature of the disease.
A new method, the so-called Alpha-Synuclein Seed Amplification Assay (αSyn-SAA), now enables the protein to be detected in the cerebrospinal fluid. In a study, a team led by Andrew Siderowf from the University of Pennsylvania examined 1,123 people, including patients diagnosed with Parkinson’s disease, people with frequent pre-cancerous stages of the disease and healthy people.
Protein found in 88 percent of Parkinson’s patients
The test found the protein in 88 percent of Parkinson’s patients. In people with the sporadic form of the disease, the hit rate was even 93 percent, in patients with the genetic risk factor GBA it was 96 percent. In patients with the LRRK2 variant, however, the proportion was only 68 percent – here studies indicate a possible different mechanism of the disease.
In people with pre-Parkinson’s disease, the hit rate depended heavily on the symptoms: If the sense of smell was impaired, the misfolded protein was detectable in a good 97 percent of the participants. In people with a dream sleep disorder, the proportion was only 63 percent.
Very early warning possible
Particularly important: In most participants with a pre-Parkinson’s disease in which the protein was present in the cerebrospinal fluid, there was no evidence of changes in the nerve cells in the substantia nigra. From this, the team deduces that alpha-synuclein can be a very early indication of the developing disease.
“The core problem with Parkinson’s is that we are too late with the therapies,” explains Timmermann, Director of the Department of Neurology at the University Hospital in Marburg. “We need to be able to identify patients before the brain is damaged.” The study shows that this is possible with the method examined.
This is also emphasized by the authors of the study: “Our results indicate that the αSyn-SAA method determines the biomarker for Parkinson’s disease very reliably,” says co-author Luis Concha from the biotechnology company Amprion in a “Lancet”. -Notice quoted. This makes it possible to diagnose the disease in the early stages. Apparently, the misfolded proteins spread before brain damage could be detected.
Lower hit rate for certain gene variants
However, the authors of the study emphasize that the method has proven to be less reliable in people with the gene variant LRRK2 and an unimpaired sense of smell: Here the hit rate was only around 35 percent. For women in this group, it was just under 13 percent.
The authors emphasize that these findings would have a direct impact on the planning of clinical trials. When examining therapies for people with the LRRK2 gene variant, the αSyn-SAA finding must be taken into account. Similarly, with therapies targeting alpha-synuclein, one should consider the possibility that people without accumulation of the misfolded protein may respond differently to treatment.
Hope for “new era” of therapies
The importance of these findings can also be seen in retrospect: in 2022, two large studies (here and here) with antibodies against alpha-synuclein failed – a major setback for Parkinson’s research. This study data could now be analyzed again, taking into account the current findings, says Timmermann.
The German commentators Berg and Klein emphasize that a “new era in the development of biomarkers and therapies” is beginning for Parkinson’s disease. The possibility of being able to detect misfolded alpha-synuclein is a groundbreaking development. However, compared to examining the brain water, a less invasive blood test would be desirable. It was only recently that this was possible in principle Study shown. DGN President Timmermann can imagine that findings from the study could be reflected in new therapies in about five years.