Blizard Institute - Barts and The London

Neurodegeneration

 

Lead:  Dr Andrea Malaspina

The group’s main focus of research is the identification of neurochemical signals of neurodegeneration in tissues and biofluids that can be used to model novel biomarkers and therapeutics for neurodegenerative disorders. These molecular signatures include disordered proteins like neurofilaments, which can be found in a soluble state or assembled into aggregates. Research activity encompasses metabolic and immune responses which accompany neurodegeneration, like for example the formation of antibodies against axonal proteins and their potential role in disease propagation. Contributing to this research endeavor, basic scientists and clinicians working across NHS and Academia, in partnership with Industry, ensure a multi-modal approach to develop the next generation biomarkers and to identify disease mechanisms and novel target of therapeutic intervention for neurological conditions which are becoming significantly more prevalent in the ageing population. 

 

The strength of the Neurodegeneration group is the link between basic science and precision medicine, the ideal setting to develop novel point-of-care diagnostics. The Unit is part of UK-based and International networks of biorepositories, with one of the world’s largest longitudinal collections of clinical data and biological samples from individuals with amyotrophic lateral sclerosis and other neurodegenerative disorders. This ex-vivo approach is the biological substrate for the study of systemic phenomena that mirror brain pathology.

The critical questions the group seeks to answer are: what are the driving forces behind the variable rate of disease progression in neurodegeneration? What conditions the development of the phenotypic extremes seen in fatal neurodegenerative disorders like amyotrophic lateral sclerosis? Which biological features of disease risk can inform on a pre-symptomatic stage of neurodegeneration in the general population?

Biological mechanisms linked to neurodegeneration and ageing, including altered protein homeostasis, metabolism and neuroinflammation are investigated to enhance clinical stratification and improve clinical trial designs. The goal is to overcome the current impasse in the development of effective treatments for neurodegeneration through better diagnostics and the characterization of the pathological processes underpinning neurodegenerative disorders.

Research Lines

  • Characterization of structural and inflammatory biomarkers in biofluids from individuals affected by neurodegenerative disorders and from animal models of the disease.
  • Neurofilament-containing circulating protein aggregates as a readout of neurodegeneration.
  • Tissue-enhanced TMT calibrator biofluid proteomics in neurodegeneration
  • The interplay between metabolism, cell senescence and inflammation in the development of neurodegeneration
  • Tracking the natural history of amyotrophic lateral sclerosis from a pre-symptomatic stage and during disease progression using neurochemical markers
  • The antibody-response to disordered axonal proteins in phenotypic extremes of neurodegeneration
  • Longitudinal and orthogonal biobanking using remote collection and energy efficient storage.

Ozlem Yildiz, AMBRoSIA Clinical Research Assistant, PhD student, Blizard Institute

Rocco Adiutori, MRC Industrial Case PhD Student, Blizard Institute

Fabiola Puentes, Research Assistant, Blizard Institute

Vittoria Lombardi, Research Assistant, Blizard Institute

Yoanna Bobeva, Laboratory Research Assistant, North-Thames CLRN, Blizard Institute

Georgina Butt, Research Coordinator, Research and Development, Basildon University Hospital

Kezia Allen, Laboratory Research Technician, Research and Development, Basildon University Hospital

Pietro Fratta, Clinician Scientist, UCL Institute of Neurology 

Luca Zampedri, Research Nurse, UCL Institute of Neurology 

 

 

 

Benatar M, Wuu J, Andersen P, Lombardi V, Malaspina A. Neurofilament light: Biomarker of pre-symptomatic ALS and phenoconversion. Ann Neurol. 2018; doi: 10.1002/ana.25276. PMID: 30014505

Elisabetta Zucchi, Ching-Hua Lu, Yunju Cho, Rakwoo Chang, Rocco Adiutori, Irene Zubiri, Mauro Ceroni, Cristina Cereda, OriettaPansarasa, Linda Greensmith, Andrea Malaspina, Axel Petzold. A motor neuron strategy to save time and energy in neurodegeneration: adaptive protein stoichiometry. J Neurochem. 2018. doi: 10.1111/jnc.14542. PMID: 29959860.

Adiutori R, Aarum J, Zubiri I, Bremang M, Jung S, Sheer D, Pike I, Malaspina A. The proteome of neurofilament-containing proten aggregates in blood. Biochem Biophys Rep. 2018 25; 14:168-177. PMID: 29872749.

Lu CH, Allen K, Oei F, Leoni E, Kuhle J, Tree T, Fratta P, Sharma N, Sidle K, Howard R, Orrell R, Fish M, Greensmith L, Pearce N, Gallo V, Malaspina A. Systemic inflammatory response and neuromuscular involvement in amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2016; PMID: 27308305.

Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015; 84: 2247-57. PMID: 25934855.

Menke RA, Gray E, Lu CH, Kuhle J, Talbot K, Malaspina A, Turner MR. CSF neurofilament light chain reflects corticospinal tract degeneration in ALS. Ann Clin Transl Neurol. 2015 Jul;2(7):748-55. doi: 10.1002/acn3.212. Epub 2015 May 25. PMID: 26273687.

Malaspina A, Puentes F, Amor S. Disease origin and progression in amyotrophic lateral sclerosis: an immunology perspective. Int Immunol 2015; 27: 117-29.  PMID: 25344935.

Lu CH, Petzold A, Topping J, Allen K, Macdonald-Wallis C, Clarke J, Pearce N, Kuhle J, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Greensmith L, Malaspina A. Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study. J Neurol Neurosurg Psychiatry 2015; 86: 565-73. PMID: 25009280.

Puentes F, Topping J, Kuhle J, van der Star BJ, Douiri A, Giovannoni G, Baker D, Amor S, Malaspina A. Immune reactivity to neurofilament proteins in the clinical staging of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 2014; 85: 274-8. PMID: 24078718.

Dr Andrea Malaspina
a.malaspina@qmul.ac.uk Tel: +44 (0)20 7882 6239 Fax: +44 (0)20 7882 2180

Ms Jyoti Salhan
j.salhan@qmul.ac.uk Tel: +44 (0)20 7882 8605 Fax: +44 (0)20 7882 2180

Centre for Neuroscience, Surgery and Trauma
Blizard Institute
Barts and The London School of Medicine and Dentistry
4 Newark Street
London
E1 2AT