CHDR is contributing to the development of new drugs against neurodegeneration. We are developing biomarkers to demonstrate a compound’s effects in healthy volunteers, and at the same time we are expanding our abilities to perform research in patients with Alzheimer’s disease and other neurodegenerative diseases, such as Multiple Sclerosis, Parkinson's Disease or epilepsy. CHDR’s staff includes two board-certified neurologists with clinical positions in academic medical hospitals in Leiden and Amsterdam.

Using biomarkers to measure the action of next-generation CNS drugs

New drugs are currently being developed to slow disease progression in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and ALS. However, it is often not possible to measure the pharmacodynamic effects of these compounds in healthy subjects. Usually, CHDR’s solution is to use a challenge model, in which we temporarily and safely induce a symptom in a healthy subject. For example, to measure the effects of cholinergic drugs on cognition, a healthy subject can be given an anticholinergic compound (e.g. scopolamine or mecamylamine), thereby experiencing a temporary decrease in cognitive performance. In this context, the test compound can then be administered, and its ability to restore cognitive function can be measured. Geert Jan Groeneveld, Research Director: "In the case of enzyme inhibitors designed to stop neurodegeneration, such a challenge model would be ethically irresponsible. Nevertheless, we plan to measure the effect of the test compound on pharmacodynamics in the earliest stages of the drug’s development."

Pharmalogical Challenge Models

Genotyping 3000 Parkinson’s patients

Putting the Monocentre and Ready-for-Research strategies into practice: Genotyping 3000 Parkinson’s patients.

Imagine if the only way you could find a needle would be to search through every haystack. Now imagine that you need to find forty needles. CHDR recently faced such a challenge when asked by a sponsor to perform a study in patients who have Parkinson’s disease and a rare mutation present in only 5-10% of all patients with Parkinson’s disease. To meet this challenge, we turned to our extensive network and were able to find more than enough patients. Thanks to our extensive network in the Netherlands, a large number of patients with Parkinson’s disease received a letter from their neurologist informing them of our study and inviting them to send us a signed informed consent form and a saliva sample for DNA analysis. Our collaborators at neighbouring GenomeScan developed a method to rapidly scan the GBA gene for mutations and then used this method to analyse the nearly 3000 samples that we received. If the test compound is ultimately approved for use, it will target a specific subpopulation of PD patients and will be used together with a companion diagnostic test to screen for mutations in the GBA gene. We’re now ready for the next step: investigating the effects of the candidate drug in our target patient population. For the clinical trial, the participating patients will come to CHDR. Using this approach, which we call our Monocentre strategy, will allow us to minimise variability in terms of both the tests and the measurements (including highly sensitive testing of enzyme activity in white blood cells). And of course, the 3000 DNA samples from patients with Parkinson’s disease could potentially be used for other purposes, including genetics studies and studies related to the development of specific treatments.

Alzheimer's disease

Most hospitals in the Netherlands have an outpatient clinic that specialises in elderly patients with impaired memory and/or cognitive function. In addition to providing diagnostic facilities (for example to determine whether a patient has a treatable condition or a non-treatable form of dementia), these clinics offer advice and guidance to patients with Alzheimer’s disease and their families. To tap into this valuable network, CHDR is establishing collaborations with these outpatient clinics, thereby facilitating the recruitment of patients with Alzheimer’s disease who may wish to participate in upcoming drug trials.

- Standard diagnostic CSF (Aβ1-42, tau,p-tau)

- Hippocampal volumetry (MRI)

- Amyloid PET (PIB, florbetapir, flutemetamol)


- 36-h CSF sampling capabilities

- Pharmacological challenge models

Multiple Sclerosis

The MS Center Amsterdam is visited by about 50% of all newly diagnosed MS patients in the Netherlands. The center, headed by prof. Chris Polman, is one of the top five MS research groups in the world. It includes more than 60 researchers of different disciplines who collaborate to answer questions regarding the cause and cure of MS.

- MTR (magnetization transfer ratio) for demyelination

- DTI (diffusion tensor imaging)

- H/M ratio (EMG) for spasticity

- Double inversion recovery 3T MRI imaging for detection of MS lesions

Myelin turnover quantification using D2O labelling

Other patient Populations

  • Parkinson's Disease
  • Dementia
  • Lewy Body Dementia
  • Frontotemporal dementia
  • Vascular Cognitive impairment
  • Epilepsy

  • Essential Tremor
  • Migraine and cluster headaches

Patient recruitment strategies 

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