Research Center for ALS

Head

Valentina Bonetto

valentina.bonetto@marionegri.it

The Research Center for Amyotrophic Lateral Sclerosis (ALSCenter) brings together the groups that are involved in ALS research at the Institute, from an epidemiological, preclinical and translational point of view. It also coordinates the regional population-based registry of ALS and carries out activities in support to clinical studies.

ALS is a severe neurodegenerative disease of adulthood that affects motor neurons, the cells responsible for muscle contraction, a condition that leads to paralysis and consequent atrophy of the voluntary muscles of the whole body, finally involving the respiratory muscles. A therapy for ALS to date has not yet been developed. Only in about 10% of patients the disease is due to genetic mutations, in most cases the cause is unknown. It is hypothesized that ALS is caused by a combination of factors: genetic predisposition, environmental factors and processes associated with aging. ALSCenter research aims to understand which of these elements are the most important to hit, how and when, in order to stop or slow down the disease. It also aims to identify biomarkers to support diagnosis and prognosis and useful for monitoring the progression of the disease and the efficacy of therapies.

Aims/Objectives

Research lines

Study of pathogenetic mechanisms in experimental models to identify new and more effective drug targets,
Role of neuroinflammation and immune response,
Study of muscle atrophy in in vitro and in vivo models;
Development and implementation of research methods and tools (animal and cellular models, biochemical assays, innovative technologies, trial designs);
Identification and validation of biomarkers in preclinical and clinical studies;
Epidemiological studies on risk and prognostics factors, quality of life and outcomes;
Identification of molecules to test in experimental clinical studies.

METHODOLOGICAL APPROACHES

Services offered‍

Pharmacological studies in animal models;‍
In vivo assessment of muscle atrophyusing MyoRep technology;
Analysis of biomarkers in biofluids for observational and interventionalclinical studies;
Support activities for observational and interventional clinical studies(CRO);
Statistical analysis for clinical studies;
Biobanking of samples from patients and animal models.

Current projects

MultiTreatALS - A multisystem and multitarget therapeutic approach to hamper Amyotrophic Lateral Sclerosis

Sponsor: FRRB - Fondazione Regionale per la Ricerca Biomedica

ALCALS - A randomized, phase II/III trial on the biological and clinical effects of acetyl-L-carnitine in ALS

Sponsor: FightMND Australia

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PERMEALS - Towards a PERsonalized MEdicine in amyotrophic lateral sclerosis (ALS) by a patient-tailored genetic/biomarker/iPSC combined approach

Sponsor: Ministero della Salute, PNRR

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GATTALS - A gene therapy approach targeting TDP-43 pathology in ALS

Sponsor: AriSLA- Fondazione Italiana di Ricerca per la SLA

EVTestInALS - Extracellular vesicles in ALS: testing their use as biomarkers for prognosis and disease progression

Sponsor: AriSLA- Fondazione Italiana di Ricerca per la SLA

A mechanism-based gene therapy approach for TDP-43 proteinopathies: a proof-of-concept study in frontotemporal dementia and traumatic brain injury

Sponsor: Fondazione Cariplo

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TDP-43 pathology and Lys-acetylation in circulating lymphomonocytes as biomarkers and therapeutic hints for amyotrophiclateral sclerosis

Sponsor: Ministero della Salute, Ricerca Finalizzata

Intramuscular allosteric agonism of purinergic P2X7 receptor as a pharmacological approach to enhance skeletal muscleregeneration in Amyotrophic Lateral Sclerosis; Drug Development Grants

Sponsor: FightMND Australia

Dissecting the role of the myokine musclin against amyotrophic lateral sclerosis-induced muscle atrophy

Sponsor: AFM Association Française Contre Les Myopathies -Trampoline Grant

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