Dr Viorica Chelban

2021 Post-doctoral Clinical Fellowship

Insights into MSA pathogenesis and pathways for biomarkers discovery

Multiple system atrophy (MSA) is a rare neuropathologically defined disease characterised by the formation of alpha-synuclein (α-syn) positive glial-cytoplasmic-inclusions. A challenging clinical picture is emerging with significant variability in survival times, disease severity and rate of progression. The genetic determinants of clinical progression and survival for neurodegenerative diseases are largely unexplored and are likely to provide important biological insights that might lead to new therapeutic approaches. However, very few breakthroughs in the underlying genetics of MSA have been made. No studies assessing genetic architecture and survival have been performed in MSA. Furthermore, an other important limitation in MSA drug trial design and patient stratification is the lack of validated biomarkers that reflect progression and severity.

The overall goal is to comprehensively study the genetic risks, determinants of survival and the alpha-synuclein (SNCA) region in detail in MSA. I plan to achieve this through the following aims: 1. To analyse (a) genetic risks and (b) determinants of survival in individuals with pathologically confirmed MSA. 2. To investigate the key pathological molecule in MSA: the SNCA and SNCA Antisense RNA 1 (SNCA-AS1) region using RNA sequencing. 3. Establish a disease staging profile based on fluid biomarkers and brain atrophy rate (on MRI) over time. I will perform the genetic analyses in pathologically confirmed MSA cases exclusively, to ensure the highest possible diagnostic accuracy.

Viorica was awarded Principal Investigator grant funding in 2023 to advance basic science and clinical research into MSA and was promoted to Senior Clinical Research Fellow at Queen Square Institute of Neurology, UCL. She was also appointed Chief Investigator for an MSA drug trial.

Publications

Biallelic NAA60 Variants with Impaired N-terminal Acetylation Capacity Cause Autosomal Recessive Primary Familial Brain Calcifications

Chelban V, Aksnes H, Maroofian R, LaMonica L, et al.

Nature Communication, accepted in Dec 2023

2023

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials

Street D, Jabbari E, Costantini A, Jones PS, Holland N, Rittman T, Jensen MT, Chelban V, Goh YY, Guo T, Heslegrave AJ, Roncaroli F, Klein JC, Ansorge O, Allinson KSJ, Jaunmuktane Z, Revesz T, Warner TT, Lees AJ, Zetterberg H, Russell LL, Bocchetta M, Rohrer JD, Burn DJ, Pavese N, Gerhard A, Kobylecki C, Leigh PN, Church A, Hu MTM, Houlden H, Morris H, Rowe JB

Brain. 2023 Aug 1;146(8):3232-3242. doi: 10.1093/brain/awad105

2023

Multiple system atrophy

Goh YY, Saunders E, Pavey S, Rushton E, Quinn N, Houlden H, Chelban V

Practical Neurology 2023 Jun;23(3):208-221. doi: 10.1136/pn-2020-002797

2023

Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in VPS13D-Related Disorder

Pauly, M. G., Brüggemann, N., Efthymiou, S., Grözinger, A., Diaw, S. H., Chelban, V., Turchetti, V., Vona, B., Tadic, V., Houlden, H., Münchau, A., & Lohmann, K

International journal of molecular sciences, 24(3), 1874, doi: 10.3390/ijms24031874

2023

Phenotypic continuum of NFU1-related disorders

Kaiyrzhanov, R., Zaki, M. S., Lau, T., Sen, S., Azizimalamiri, R., Zamani, M., Sayin, G. Y., Hilander, T., Efthymiou, S., Chelban, V et al.

Annals of clinical and translational neurology, 9(12), 2025–2035

2022

Diagnosing Premotor Multiple System Atrophy: Natural History and Autonomic Testing in an Autopsy-Confirmed Cohort

Vichayanrat, E., Valerio, F., Koay, S., De Pablo-Fernandez, E., Panicker, J., Morris, H., Bhatia, K., Chelban, V., Houlden, H., Quinn, N., Navarro-Otano, J., Miki, Y., Holton, J., Warner, T., Mathias, C., & Iodice, V

Neurology, 99(11), e1168–e1177, doi: 10.1212/WNL.0000000000200861

2022

Combining biomarkers for prognostic modelling of Parkinson's disease

Vijiaratnam, N., Lawton, M., Heslegrave, A. J., Guo, T., Tan, M., Jabbari, E., Real, R., Woodside, J., Grosset, K., Chelban, V et al.

Journal of neurology, neurosurgery, and psychiatry, 93(7), 707–715, doi: 10.1136/jnnp-2021-328365

2022