Dr Emily Feneberg

2020 Post-doctoral Clinical Fellowship

Absolute quantification of pathological TDP-43

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

SARS-CoV-2 and neurodegenerative diseases: what we know and what we don't

Lingor P, Demleitner AF, Wolff AW, Feneberg E

Journal of Neural Transmission (Vienna) 2022 Sep;129(9):1155-1167. doi: 10.1007/s00702-022-02500-w

2022

Atypical TDP-43 protein expression in an ALS pedigree carrying a p.Y374X truncation mutation in TARDBP

Cooper-Knock J, Julian TH, Feneberg E, Highley JR, Sidra M, Turner MR, Talbot K, Ansorge O, Allen SP, Moll T, Shelkovnikova T, Castelli L, Hautbergue GM, Hewitt C, Kirby J, Wharton SB, Mead RJ, Shaw PJ

Brain Pathololgy 2023 Jan;33(1):e13104. doi: 10.1111/bpa.13104

2023

Proteinopathy Specific Biomarker Development

Cordts I, Wachinger A, Scialo C, Lingor P, Polymenidou M, Buratti E, Feneberg E

Cells. 2023 Feb 12;12(4):597. doi: 10.3390/cells12040597

2023

Advantages of routine next-generation sequencing over standard genetic testing in the amyotrophic lateral sclerosis clinic

Scaber J, Thompson AG, Farrimond L, Feneberg E, Proudfoot M, Ossher L, Turner MR, Talbot K

European Journal of Neurology 2023 Aug;30(8):2240-2249. doi: 10.1111/ene.15855

2023

Parkinson's disease therapy: what lies ahead?

Wolff A, Schumacher NU, Pürner D, Machetanz G, Demleitner AF, Feneberg E, Hagemeier M, Lingor P

Journal of Neural Transmission (Vienna). 2023 Jun;130(6):793-820. doi: 10.1007/s00702-023-02641-6

2023

Multicentre appraisal of amyotrophic lateral sclerosis biofluid biomarkers shows primacy of blood neurofilament light chain

Thompson AG, Gray E, Verber N, Bobeva Y, Lombardi V, Shepheard SR, Yildiz O, Feneberg E, Farrimond L, Dharmadasa T, Gray P, Edmond EC, Scaber J, Gagliardi D, Kirby J, Jenkins TM, Fratta P, McDermott CJ, Manohar SG, Talbot K, Malaspina A, Shaw PJ, Turner MR

Brain Communication 2022 Feb 9;4(1):fcac029. doi: 10.1093/braincomms/fcac029

2022

Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS

Halbgebauer S, Steinacker P, Verde F, Weishaupt J, Oeckl P, von Arnim C, Dorst J, Feneberg E, Mayer B, Rosenbohm A, Silani V, Ludolph AC, Otto M

Journal of Neurology, Neurosurgery, and Psychiatry 2022 Jan;93(1):68-74. doi: 10.1136/jnnp-2021-327129

2022

Detection and quantification of novel C-terminal TDP-43 fragments in ALS-TDP

Feneberg E, Charles PD, Finelli MJ, Scott C, Kessler BM, Fischer R, Ansorge O, Gray E, Talbot K, Turner MR

Brain Pathology 2021 Jul;31(4):e12923. doi: 10.1111/bpa.12923.

2021

Advancing mechanistic understanding and biomarker development in amyotrophic lateral sclerosis

Thompson AG, Oeckl P, Feneberg E, Bowser R, Otto M, Fischer R, Kessler B, Turner MR

Expert Review of Proteomics 2021 Nov;18(11):977-994. doi:10.1080/14789450.2021.2004890

2021

Chitotriosidase as biomarker for early stage amyotrophic lateral sclerosis: a multicenter study

Steinacker P, Feneberg E, Halbgebauer S, Witzel S, Verde F, Oeckl P, Van Damme P, Gaur N, Gray E, Grosskreutz J, Jardel CG, Kachanov M, Kuhle J, Lamari F, Maceski A, Del Mar Amador M, Mayer B, Morelli C, Petri S, Poesen K, Raaphorst J, Salachas F, Silani V, Turner MR, Verbeek MM, Volk AE, Weishaupt JH, Weydt P, Ludolph AC, Otto M

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 2021 May;22(3-4):276-286. doi: 10.1080/21678421.2020.1861023

2021

Amyotrophic lateral sclerosis with a heterozygous D91A SOD1 variant and classical ALS-TDP neuropathology

Feneberg E, Turner MR, Ansorge O, Talbot K

Neurology

Sep 2020, 95 (13) 595-596; DOI: 10.1212/WNL.0000000000010587

Detection and Quantification of Novel C-terminal TDP-43 Fragments in ALS-TDP

Feneberg E, Charles PD, Finelli MJ, Connor S, Kessler BM, Fischer R, Ansorge O, Gray E, Talbot K, Turner MR

Brain Pathol.

2020 Dec 10:e12923. doi: 10.1111/bpa.12923.

An ALS-linked mutation in TDP-43 disrupts normal protein interactions in the motor neuron response to oxidative stress

Feneberg E, Gordon D, Thompson AG, Finelli MJ, Dafinca R, Candalija A, Charles PD, Mäger I, Wood MJ, Fischer R, Kessler BM, Gray E, Turner MR, Talbot K

Neurobiol Dis. 2020 Oct;144:105050. doi: 10.1016/j.nbd.2020.105050

2020

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)