Method development

The key to successful therapy: early biological diagnosis of the diseases

In case of an early diagnosis of the diseases, patients get early answers to questions on how to best treat the diseases. Many effective therapies already exist for MS, which should be used early on to avoid relapses and an increase in disability. Meanwhile, there are more and more treatment approaches for the insidious phase of the disease, which, however, are often used too late if they are recognised too late. For Parkinson’s and Alzheimer’s disease, only symptomatic therapies are available so far, which are also applied early, but cannot yet treat the causes of the disease. It is generally agreed, however, that also for these diseases it is necessary to diagnose the diseases as early as possible in order to effectively initiate the entire treatment strategies. The development of causal therapies for Parkinson’s and Alzheimer’s is currently underway with many different approaches.

A special opportunity arises when biological markers can be used to detect the disease already in the so-called prodromal stage, i.e. when the disease is biologically developing in the body but the patient does not experience symptoms.

Biomarkers are biological markers that can indicate and reflect the body’s own pathological, but also healthy, intact processes. They make it possible to diagnose diseases more easily and earlier and to classify or predict the course of a disease. This makes it possible to intervene in the disease process at an early stage, to start therapies as early as possible and thus to prevent or slow down the progression of the disease. The focus is therefore on finding specific biomarkers or biomarker patterns that characterise and differentiate the various neurodegenerative diseases.

Previous methods in the diagnosis of neurodegenerative diseases

In the clinic, the diagnosis of Parkinson’s disease, for example, is primarily based on the clinical neurological examination. This is supported by imaging procedures such as cMRI, DaTSCAN or SPECT, and the L-Dopa Response Test. The biological diagnosis of Alzheimer’s disease is currently one step ahead of that of Parkinson’s disease. In recent years, biomarkers in the cerebrospinal fluid – nervous fluid that surrounds and protects our brain – have been identified and validated. In addition to neuropsychological tests and imaging (cMRI, cCT and PET), neurochemical biomarker analysis is now also being carried out. The biomarkers amyloid-β and tau help to make the diagnosis more certain and to identify possible risk patients in early stages.

Clinic and research go hand in hand

Parkinson’s patients can already participate in various studies at our clinical research centre, which are designed to help characterise the course of the disease more clearly over a longer period of time, to clarify the significance of comorbidities and to test the effectiveness of therapies. The Park Move Study, for example, examines the individual movement profile of patients with the help of wearables (sensors) in order to investigate the effectiveness of the two-week multimodal Parkinson’s complex therapy. The Parkinson Nerve Study is a long-term study that focuses on idiopathic and atypical Parkinson’s patients. It is concerned with the progression of Parkinson’s disease and with additional or concomitant comorbidities of the peripheral nervous system.

Our contribution: Development of innovative methods for early diagnosis

Currently, the available methods for the early diagnosis of Parkinson’s and Alzheimer’s disease in particular, as well as the progressive phase of MS, are insufficient. Our goal is therefore to develop procedures in the multidisciplinary environment of PRODI that will enable or strengthen the early diagnosis of Alzheimer’s, Parkinson’s and progressive MS. These methods are based on the analysis of proteins associated with the disease such as amyloid-β (Aβ), tau or alpha-synuclein as well as markers for nerve cell degradation such as neurofilament in body fluids. In addition to developing specific protein and spectral biomarkers for (early) diagnosis, we are also working to better understand the diseases at the molecular level. In this way, we not only want to improve diagnostics, but also better evaluate the effects and efficacy of new curative drugs.

Biomarkers can be analysed in body fluids, but also in tissues. In Parkinson’s disease, the focus is on cerebrospinal fluid and skin biomarkers. Special attention is paid to the cerebrospinal fluid. Due to its proximity to brain tissue, changes in the protein composition in the CSF could be used to map altered processes in the brain. In cooperation with the Biophysics Section of the ProDi, extensive proteome analyses of the cerebrospinal fluid of Parkinson’s patients from the clinic are carried out. These serve to detect and validate diagnostically and prognostically significant CSF biomarkers. In addition, alpha-synuclein aggregations in the peripheral cutaneous nerves can be relevant for early diagnosis. In cooperation with the Centre for Clinical Research (ZKF), skin samples that can easily be taken by means of skin biopsies are prepared and analysed. In addition, the investigation of a structural protein of nerve cells, neurofilament, in the cerebrospinal fluid of MS patients is taking place.