Genotyped cohort facilitates recruitment for studies in Parkinson's Disease

‘This is a very interesting time in the development of new treatments for neurodegenerative disorders,’ says Dr Philip Kremer, Director of Neurology. ‘Thanks to the growing knowledge about neurodegenerative pathways and the associated pharmacological targets, we are seeing more and more drugs that are able to slow down the disease process. These are often aimed at subgroups of patients in whom a specific pathophysiological pathway is of particular importance new to inherited traits. We can contribute to the study of these drugs, especially in PD, thanks to our previous work on genotyping PD patients.’

An important basis for CHDR’s easy recruitment of PD patients with specific genetic characteristics is a genetic screening study carried out by the Neurology group in 2017 and 2018. In collaboration with neurologists throughout the country, more than 3,500 patients were recruited. DNA material was collected via saliva swabs, which was used for genotyping. For example, variants in the gene for the lysosomal enzyme glucocerebrosidase (GCase) were studied. In the years that followed, CHDR remained in contact with these neurologists, and the database with genotyped PD patients has already grown to 5,000 patients.

‘Our collaboration with neurologists is in the interests of patients and our sponsors,’ says Kremer. Thanks to this collaboration, patients can participate in trials with innovative medicines, often with the possibility of a months-long extension after completion of the study. For our clients, this means that we have quick access to sufficient patients with exactly the right genetic profile. And of course, our scientific collaboration with these neurologists is in our mutual interest as well.’

A good example of the above is the study conducted by the Neurology Group with a new allosteric activator of lysosomal GCase. Loss of function of this lysosomal enzyme is the most common genetic risk factor for PD. As a result of a mutation, the activity of the enzyme is reduced. This causes the lysosome to function less effectively, resulting in the accumulation of alpha synuclein in neurons, causing the neurodegeneration characteristic of PD. Restoring the function of this enzyme has the potential to slow the progression of PD. “In this new study, initiated in 2024, we were able to specifically measure GCase activity in response to the investigational molecule, something that could not be done in the 2018 study”.

‘We have conducted both first-in-human studies in healthy participants and initial studies in selected patients with PD due to GCase loss of function,’ says Kremer. In the Single and Multiple Ascending Dose (SAD/MAD) studies in healthy study participants, the team was able to demonstrate that the drug is safe and reaches its target in the brain. It could also be shown that the drug increases GCase activity in a dose-dependent manner. Building on these results, the study was conducted in patients, a 28-day placebo-controlled study with a 3- or 6-month open-label extension. The first results are promising and confirm the pattern seen in healthy participants. GCase activity in patients increases to the level of people without the mutation of the same age group.

Kremer: ‘We are, of course, curious to see how the further development of this drug progresses. For us, this study is a valuable follow-up to our previous work on this debilitating condition. We hope to contribute to the development of better treatments for PD and similar neurodegenerative diseases.’