Metabolomic characterization of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system with a strong autoimmune component. MS is the most common cause of non-traumatic acquired neurological disability in young adults with a particularly high incidence in Sardinia. Several aspects still represent an active challenge in the clinical management of MS, such as the early diagnosis, the classification of the patients, the response to the therapy and the influence of the hormonal alteration in the progression of the disease. Finding potential biomarkers useful to address all these points, represents the purpose of this thesis, in which I used the metabolomics approach to investigate three main points: 1) Classification of patients affected by different forms of MS (relapsing remitting, RRMS, and primary progressive, PPMS); 2) Monitoring of the response to the Fingolimod therapy; 3) To study the protective role of pregnancy on MS progression. Plasma, serum and cerebrospinal fluid (this only for the first study) were collected from selected MS patients and healthy subjects, and Nuclear Magnetic Resonance and Mass Spectrometry were used to measure the metabolic profile. Multivariate and univariate statistical tools were exploited to find specific patterns of metabolites based on the different MS aspect. Aim 1: statistical models allowed to define different metabolic profiles in RRMS or PPMS patients. These differences could be extremely important to explain the specific pathophysiological mechanism behind the two different MS forms (e.g. neuroinflammation vs neurodegenerative). Aim 2: treatment of MS patients with FINGO influences aminoacidic and energy metabolisms, and reduces oxidative stress and the activity of the immune system, both typical features of the disease. Aim 3: the known pregnancy's protective role can also be evinced from the metabolic point of view. Most of the metabolites changed their concentration with the same trend in healthy and MS women during pregnancy, indicating that the presence of the pregnancy is predominant in the MS. To date, metabolomics represents an innovative approach to discover putative biomolecules that, in a specific pathological contest, can open new avenues for the deep investigation of target mechanisms.

Grantor dc:publisher

Università degli Studi di Cagliari

Year dc:date

2023

Author dc:creator

• MURGIA, FEDERICA

Contributors dc:contributor

• COCCO, ELEONORA

• Settore MED/05 - Patologia Clinica

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

eng

Handle dc:identifier

https://hdl.handle.net/11584/356462

OAI identifier oai:identifier

oai:iris.unica.it:11584/356462