The diagnosis of neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) is currently difficult and imprecise in living patients. The reason is that it is based only on clinical symptoms rather than a definite pathology of disease-specific markers such as those that can be identified in the brain of patients after they have died.

TDP-43 is a normal protein that regulates important cellular functions, but in nearly all cases of ALS, half of those with FTD and 20% of Alzheimer’s dementia patients TDP-43 can be found abnormally accumulated in nerve cells of the brain and spinal cord leading to progressive cell death. Measuring the disease-relevant form of TDP-43 in the blood and spinal fluid of those patients would be the ideal biomarker that might reduce diagnostic delays and offer a readout for use in future drug trials.

During my GoB Fellowship I developed a novel and highly sensitive method to measure the disease-specific forms of TDP-43 from central nervous system tissue derived from patient’s that donated their brains after death. I have detected disease-specific forms of the TDP-43 protein, which we then used for a highly specialised mass spectrometry to directly detect those TDP-43 disease forms up to attomolar (10-18/l) concentrations in biofluids. Together this enabled the development of a technique for the absolute quantification of abnormal TDP-43 and will now be used for assay development for patient screening and stratification based on their molecular protein signature.

Publications

Patents

Filed: The invention relates to methods, compositions and kits for diagnosing a condition characterised by TDP-43 proteinopathy The application No of the patent is 2004863.3.Territory: United Kingdom, Filing Date: 2 April 2020.

Career

Specialist Neurologist at the Department of Neurology Klinikum rechts der Isar at the Technical University Munich (Germany)