PhD in Neuroscience

Contacts

Supervisor

Curriculum vitae

Phd thesis

Serum and cerebrospinal fluid proteins correlating with neurodegeneration as potential biomarkers of Central Nervous System (CNS) involvement in Neuromusclar Disorders (NMDs)

Abstract

Among Neuromuscular Disorders (NMDs), central neural damage often represents a relevant issue of the multi-systemic phenotypes, even if not overt at least initially. With the advent of more elaborated diagnostic technologies and disease-modifying therapies, easily accessible biomarkers are needed as predictive and prognostic measures. In regards to Central Nervous System (CNS) dysfunction, biochemical markers of neurodegeneration (i.e. amyloid beta-42 and -40, total-tau, phospho-tau, phosphorylated neurofilament heavy chain and neurofilament light chain) will be investigated in serum and cerebrospinal fluid of selected NMDs with clinical signs (i.e. at neuropsychological assessment) of cognitive impairment and already reported central network disorder in literature data (i.e. dystrophinopathies, Spinal Muscular Atrophy – SMA – type 5q, facioscapulohumeral muscular dystrophy, late-onset Pompe disease – LOPD). Concentrations of such biomarkers will be assessed over 3 years to follow eventual disease progression, correlating such data with those acquired from motor functional evalutations (cfr. MFM, 6MWT, WGS; QMFT and GSGC for Pompe disease only; RULM and HFMSE for SMA 5q only), neuropsychological assessments and, if amenable, with eventual response to treatments whether available (i.e. Alglucosidase-alfa/Avalglucosidase-alfa for LOPD; Nusinersen or Risdiplam for SMA 5q).

Research activities

In my capacity as a doctoral fellow specializing in clinical neuroscience with a focus on neuromuscular disorders, my research is centered around a diverse range of myopathies encompassing both genetic and acquired conditions. The primary objective of my PhD research project is to investigate a potential correlation between the progression of motor impairment, neuropsychological performance, and serum/cerebrospinal fluid (CSF) biomarkers of neurodegeneration in a prospective longitudinal manner. The study involves a two-year follow-up period and includes 50 patients diagnosed with SMA and DMD, aged over 14 years.

Throughout the course of the study, assessments will be conducted at three key time points: baseline, 12 months, and 24 months from the initiation of the study. Motor function will be evaluated using established functional motor scales such as MFM, 6MWD, HFMSE, RULM, NSAA, and PUL 2.0. To assess neuropsychological aspects, a comprehensive battery of cognitive tests will be administered by a trained neuropsychologist.

Additionally, the investigation will incorporate the analysis of neurodegeneration biomarkers, specifically NF-L, pNF-H, t-tau, p-tau, beta-amyloid-40, and -42. These biomarkers will be examined both in CSF, obtained during regular clinical procedures such as intrathecal Nusinersen treatment for SMA, and in serum samples.

Overall, my PhD research endeavors to explore the relationship between motor impairment progression, neuropsychological performance, and neurodegeneration biomarkers in patients with SMA and DMD. By employing validated functional motor scales, comprehensive neuropsychological assessments, and the analysis of relevant biomarkers, this study aims to contribute to a deeper understanding of these neuromuscular disorders and potentially inform future therapeutic interventions.

Congress participations and contributions:

Date of Presentation: 08/03/2023
Type and Title of Presentation: Poster – “Un passaggio condiviso tra medico e paziente: lo switchterapeutico intratecale-orale nella popolazione SMA adulta e pediatrica”
Title of Conference: SMAkers 2023 (Turin, Italy)

Date of Presentation: 27/05/2023
Type and Title of Presentation: Oral Communication – “Etiopathogenesis and Natural History of Pompe Disease”
Title of Conference: Late-Onset Pompe Disease: from diagnosis to multi-disciplinary care (Turin, Italy)

Date of Presentation: 09/06/2023
Type and Title of Presentation: Oral Communication – “When it is not FSHD: reviewing the mimics”
Title of Conference: Italian Association of Myology (AIM) Congress 2023 (Padua, Italy)

Date of Presentation: 15/06/2023
Type and Title of Presentation: Poster – “Discordant monozygotic twins with reduced-length D4Z4 allele and FSHD-like phenotype”
Title of Conference: FSHD Society International Research Congress 2023 (Milan, Italy)

Publications