Dottorato in PLASTICITÀ NEUROSENSORIALE

Titolo della tesi: Neuropathological and functional assessment of small nerve fibers in hereditary transthyretin amyloidosis with polyneuropathy.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a systemic disease characterized by somatic and autonomic peripheral nervous system involvement caused by mutation of the transthyretin encoding gene (TTR). Transthyretin amyloid deposition leads to progressive peripheral nerve degeneration that, if left untreated, leads to severe disability and death. In the last decade, enormous changes occurred in the management of this condition, with the availability of several effective disease-modifying drugs. These treatments changed profoundly the natural history of the disease, slowing the progression of ATTRv and increasing patients’ survival and quality of life. There are several open questions about the right timing of treatment initiation to prevent disease progression and, at the same time, avoid inappropriate and expensive treatments in asymptomatic carriers. Since small nerve fiber involvement is early and prevalent in ATTRv-PN, it appears logical to study it with the available functional and neuropathological tools to increase our knowledge about the disease. With this aim, in 2019 we started a collaborative study about neuropathological and functional assessment of small nerve fibers in ATTRv-PN involving three Italian referral centres: 1. Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University, Rome, Italy. UOS Neurofisiopatologia AOU Sant’Andrea 2. Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, Rome, Italy. UOC Neurologia Policlinico A. Gemelli 3. Department of Human Neuroscience, Sapienza University, Rome, Italy. UOC Neurologia Policlinico Umberto I This dissertation summarizes the results obtained in these years in three sections: the first two about published results and the third one about ongoing and future projects.