Late onset Lysosomal Storage Disorders (LSDs) in the differential diagnosis of neurodegenerative diseases: development of new diagnostic procedures and focus on potential pharmacological chaperones (PCs)

LYSOLATE

Funded by: Regione Toscana  
Calls: BANDO RICERCA SALUTE 2018
Start date: 2020-07-17  End date: 2025-01-16
Total Budget: EUR 720.000,00  INO share of the total budget: EUR 100.000,00
Scientific manager: Amelia Morrone   and for INO is: Calamai Martino

Organization/Institution/Company main assignee: Azienda Ospedaliero Universitaria Meyer di Firenze

other Organization/Institution/Company involved:
AOU Careggi
USL Toscana Centro
Universitá di Firenze

other INO’s people involved:

Capitini Claudia
Cicchi Riccardo
Credi Caterina
Dallari Caterina


Abstract: Lysosomal storage diseases (LSDs) are rare or ultra-rare monogenic disorders. Their incidence is probably underestimated and the diagnosis is often delayed or may be missed because many symptoms are of a general, non-specific. In adults, several common neurodegenerative disorders (Parkinson’s disease, Alzheimer’s disease) can present symptoms similar to LSDs.
The main goal of this project is to characterize the symptoms of neurodegenerative diseases which overlap with late- onset LSDs, so that available treatments can be introduced before neurological deterioration progresses.
The aim of the CNR unit is to develop new methods for the diagnosis of some LSDs. It has been demonstrated that a misregulation of GM1 content is directly involved in Hungtinton’s and Parkinson’s diseases. A diagnostic test to measure GM1 ganglioside levels in peripheral blood represents a potential diagnostic tool for a number of common neurodegenerative diseases. The reprogramming and differentiation of induced pluripotent stem cells in neurons obtained from fibroblasts of LSD patients will lead to the development of a tool for evaluating any therapy for neurodegenerative diseases.

The Scientific Results:
1) Fluorescent In Situ Staining and Flow Cytometric Procedures as New Pre-Diagnostic Tests for Sialidosis, GM1 Gangliosidosis and Niemann-Pick Type C
2) Identification of GM1-Ganglioside Secondary Accumulation in Fibroblasts from Neuropathic Gaucher Patients and Effect of a Trivalent Trihydroxypiperidine Iminosugar Compound on Its Storage Reduction
3) Hybrid lipid-AuNP clusters as highly efficient SERS substrates for biomedical applications
4) Generation of human induced pluripotent stem cell line (AOUMEYi001-A) from a patient affected by Congenital disorders of glycosylation (ALG8-CDG) using self-replicating RNA vector
5) Generation of a human induced pluripotent stem cell line from a patient with GM3 synthase deficiency using self-replicating RNA vector
6) Evaluating pathological levels of intracellular cholesterol through Raman and surface-enhanced Raman spectroscopies