Adriano Chió

• MD, FAAN
• Professor (Full) at University of Turin

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease arising from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). Here, we performed comparative cross-species transcriptomics of CSN using published snRNA-seq data from the motor cortex of ALS and control postmortem tiss...

Importance Treatment options for amyotrophic lateral sclerosis (ALS) remain suboptimal. Results from a phase 2 study of reldesemtiv in ALS suggested that it may slow disease progression. Objective To assess the effect of reldesemtiv vs placebo on functional outcomes in ALS. Design, Setting, and Participants A Study to Evaluate the Efficacy and Sa...

Background and objectives: The average survival of patients with amyotrophic lateral sclerosis (ALS) ranges from 2 to 5 years from symptom onset. However, it remains unclear whether this estimate has improved over time. The objective of this study was to analyze the survival trend of a large population-based cohort of patients with ALS over a 24-y...

Objective: In this review, we will examine the more common endpoints incorporated in randomized controlled trials (RCTs) and their strength of evidence, focusing on the definition of what constitutes a clinically meaningful change. We will also reflect on the perspective of patients and their families regarding the design of RCTs in amyotrophic lat...

Objective: Progressing respiratory weakness throughout the course of amyotrophic lateral sclerosis (ALS) is clinically associated with distressing symptoms, including dyspnea, orthopnea, and difficulty clearing secretions. Fatigue, poor sleep, and reduced quality of life are also considered to be associated with declining respiratory function. Resp...

Introduction/Aims Tofersen is approved for the treatment of amyotrophic lateral sclerosis (ALS) due to superoxide dismutase 1 mutations ( SOD1 ‐ALS). Here we report serious neurologic adverse events (AEs) that occurred in the tofersen clinical trials in people with SOD1 ‐ALS. Methods Serious neurologic AEs of myelitis, radiculitis, aseptic meningi...

Objective We aimed at evaluating the brain metabolic features of fused in sarcoma amyotrophic lateral sclerosis ( FUS ‐ALS) compared with sporadic ALS (sALS), using 2‐[fluorine‐18] fluoro‐2‐deoxy‐D‐glucose positron emission tomography (2‐[ ¹⁸ F]FDG‐PET). Methods We employed the 2‐sample t ‐test model of SPM12, implemented in MATLAB, to compare 12...

Objective The objective is to evaluate cognitive and behavioral progression and identify early predictors of these changes in a cohort of amyotrophic lateral sclerosis (ALS) patients. Methods A total of 161 ALS patients were tested at diagnosis (T0), and 107 were re‐tested after 1 year (T1) using cognitive/behavioral tests. All patients underwent...

Background and aim: Motor neuron diseases (MND) are heterogeneous and complex neurodegenerative disorders. Biomarkers could facilitate early diagnosis, prognosis determination, and patient stratification. Among the most studied biomarkers are neurofilaments, with peripherin (PRPH), a specific type predominantly expressed in peripheral nervous syste...

Background This study aimed to determine whether educational attainment—a common proxy of cognitive reserve (CR)—influences the association between motor and cognitive/behavioural outcomes in a large cohort of ALS patients without dementia. Methods N = 726 ALS patients without FTD were assessed for motor (ALSFRS‐R), cognitive (Edinburgh Cognitive...

Purpose We investigated sex‐related brain metabolic differences in Amyotrophic Lateral Sclerosis (ALS) and healthy controls (HC). Methods We collected two equal‐sized groups of male (m‐ALS) and female ALS (f‐ALS) patients (n = 130 each), who underwent 2‐[¹⁸F]FDG‐PET at diagnosis, matched for site of onset, cognitive status and King's stage. We inc...

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting from an intricate interplay between genetics and environmental factors. Many studies have explored living in rural areas as a possible risk factor for ALS, without focusing simultaneously on incidence, age at onset and phenotypic features. Objective To evaluate...

Background Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in death within a short time span (3-5 years). One of the major challenges in treating ALS is its highly heterogeneous disease progression and the lack of effective prognostic tools to forecast it. The main aim of this study was, then, to test the...

Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease that arises from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). The disease is mostly sporadic, but genetics is expected to highly contribute to disease onset and progression. Genome wide association studies identif...

Repeat expansions in the C9orf72 gene are the most common genetic cause of (ALS) and frontotemporal dementia (FTD). Like other genetic forms of neurodegeneration, pinpointing the precise mechanism(s) by which this mutation leads to neuronal death remains elusive, and this lack of knowledge hampers the development of therapy for C9orf72-related dise...

Background This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates. Methods N = 808 ALS patients without FTD were assessed for motor-functional outcomes—i.e., disease duration, severity (ALSFRS-R), prog...

DYNAMITE, an acronym for DYNamic Archetypal analysis for MIning disease TrajEctories, is a new methodology developed specifically to model disease progression by exploiting information available in longitudinal clinical datasets. First, archetypal analysis is applied to data organised in matrix form, with the aim of finding extreme and representati...

Automatic disease progression prediction models require large amounts of training data, which are seldom available, especially when it comes to rare diseases. A possible solution is to integrate data from different medical centres. Nevertheless, various centres often follow diverse data collection procedures and assign different semantics to collec...

Multiple Sclerosis (MS) is a chronic autoimmune and inflammatory neurological disorder characterised by episodes of symptom exacerbation, known as relapses. In this study, we investigate the role of environmental factors in relapse occurrence among MS patients, using data from the H2020 BRAINTEASER project. We employed predictive models, including...

To describe the natural history of ALS in Italy in terms of demographics, clinical characteristics, functional outcomes by stage, and survival. These natural history results from 2 registries in Italy highlight the high level of unmet need of patients living with ALS, with long diagnostic delays and a median survival of ~3 years.

Objective: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression. Methods: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six Europe...

Background Social cognition (SC) deficits are included in the amyotrophic lateral sclerosis-frontotemporal spectrum disorder (ALS-FTDS) revised diagnostic criteria. However, the impact of SC assessment on cognitive classification and the cognitive–behavioural correlates of SC remain unclear. This cross-sectional study aimed to assess the impact of...

Introduction: Serum heat shock protein (HSP) concentrations have been reported as potential biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigate the role of serum HSP70, HSP90, and DNAJC7 as biomarkers for ALS. Methods: Serum samples were collected from ALS patients and volunteer controls from three different clinical cohorts (i...

Objective: To analyze disease-modifying effects of percutaneous endoscopic gastrostomy (PEG) insertion for supporting nutrition, noninvasive ventilation (NIV), and tracheostomy-assisted ('invasive') ventilation (TIV) in amyotrophic lateral sclerosis (ALS). Methods: We retrospectively analyzed survival in a large population-based incident cohort...

Background and purpose The use of multiple tests, including spirometry, arterial blood gas (ABG) analysis and overnight oximetry (OvOx), is highly recommended to monitor the respiratory function of patients with motor neuron disease (MND). In this study, we propose a composite score to simplify the respiratory management of MND patients and better...

Amyotrophic Lateral Sclerosis (ALS) is an incurable deadly motor neuron disease that causes the gradual deterioration of nerve cells in the spinal cord and brain. It impacts voluntary limb control and can result in breathing impairment. ALS diagnosis is often challenging due to its symptoms overlapping with other medical conditions and many tests m...

Objective While the cognitive‐behavioral characteristics of amyotrophic lateral sclerosis (ALS) patients carrying C9orf72 pathological repeat expansion have been extensively studied, our understanding of those carrying SOD1 variants is mostly based on case reports. The aim of this paper is to extensively explore the cognitive‐behavioral characteris...

Objective To investigate sex‐related differences in amyotrophic lateral sclerosis (ALS) prognosis and their contributing factors. Methods Our primary cohort was the Piemonte and Aosta Register for ALS (PARALS); the Pooled Resource Open‐Access ALS Clinical Trials (PRO‐ACT) and the Answer ALS databases were used for validation. Survival analyses wer...

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are chronic diseases characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, cognitive). Patients have to manage alternated periods in hospital with care at home, experiencing a constant uncertainty regarding the timing of the disease acu...

Background This update of the guideline on the management of amyotrophic lateral sclerosis (ALS) was commissioned by the European Academy of Neurology (EAN) and prepared in collaboration with the European Reference Network for Neuromuscular Diseases (ERN EURO‐NMD) and the support of the European Network for the Cure ALS (ENCALS) and the European Or...

Background and purpose Thalamic alterations have been reported as a major feature in presymptomatic and symptomatic patients carrying the C9orf72 mutation across the frontotemporal dementia–amyotrophic lateral sclerosis (ALS) spectrum. Specifically, the pulvinar, a high‐order thalamic nucleus and timekeeper for large‐scale cortical networks, has be...

The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) was developed more than 25 years ago as an instrument to monitor functional change over time in patients with ALS. It has since been revised and extended to meet the needs of high data quality in ALS trials (ALSFRS-R), however a full re-validation of the scale was not completed. Des...

Respiratory failure assessment is among the most debatable research topics in amyotrophic lateral sclerosis (ALS) clinical research due to the wide heterogeneity of its presentation. Among the different pulmonary function tests (PFTs), maximal voluntary ventilation (MVV) has shown potential utility as a diagnostic and monitoring marker, able to cap...

Objective Noninvasive mechanical ventilation (NIMV) improves amyotrophic lateral sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Here, we test whether NIMV use changed the rate of functional decline among ALS patients. Methods In this retrospective observational study, we inclu...

Background and objectives: TARDBP patients are considered particularly prone to cognitive involvement, but no systematic studies of cognitive impairment in TARDBP patients are available. The aim of this article was to depict in depth the cognitive-behavioral characteristics of a cohort of patients with amyotrophic lateral sclerosis (ALS) carrying...

Objectives: This study assessed the feasibility of using the Milano-Torino staging (MiToS) system for conducting economic evaluation to measure health outcomes in amyotrophic lateral sclerosis (ALS). Methods: A Markov model was developed using the MiToS system and evaluated with a hypothetical treatment versus standard of care. Health utilities...

Objective The resting‐state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. Methods Here we studied the network‐to‐network connectivity of 19 ALS patients carrying the C9orf7 2 hexanucleotide repeat expansion ( C9orf72...

Background Structural variants range from simple loss or gain of genetic material to complex events that restructure entire chromosomes. This heterogeneity coupled with variant size greater than sequencing read‐length makes structural variant mapping from short‐read sequencing data difficult and error‐prone. Consequently, the role of structural var...

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer’s disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with risk of developing Lewy body dementia, we performed a population-based case-control study of 148,170 United States Medic...

Recently, pathogenic expansions (range 40–64 CAG repeats) in the HTT gene have been found in patients diagnosed with pure frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS). We report a mother with Huntington's disease (HD) associated with motor neuron disease (MND) signs and her daughter suffering from ALS with subtle signs of HD, bot...

Background Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved tre...

Recent evidence supports an association between amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). Indeed, prospective population-based studies demonstrated that about one-third of ALS patients develop parkinsonian (PK) signs, even though different neuronal circuitries are involved. In this context, proteomics represents a valuable t...

Background Uric acid (UA) has emerged as a factor that can modify cognitive function both in the general population and in people with neurodegenerative disorders. Since very few data are available concerning amyotrophic lateral sclerosis (ALS), we explored the correlation of UA levels and cognitive impairment in a large cohort of ALS patients. Me...

Spinocerebellar ataxias (SCAs) are a heterogenous group of rare neurodegenerative conditions sharing an autosomal dominant pattern of inheritance. More than 40 SCAs have been genetically determined. However, a systematic review of SCA epidemiology in Europe is still missing. Here we performed a narrative review of the literature on the epidemiology...

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are chronic diseases that cause progressive or alternating neurological impairments in motor, sensory, visual, and cognitive functions. Affected patients must manage hospital stays and home care while facing uncertainty and significant psychological and economic burdens that also affec...

Background Uncovering distinct features and trajectories of amyotrophic lateral sclerosis (ALS) associated with SOD1 mutations (SOD1-ALS) can provide valuable insights for patient’ counseling and stratification for trials, and interventions timing. Our study aims to pinpoint distinct clinical characteristics of SOD1-ALS by delving into genotype–phe...

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m²...

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder determined by a combination of both genetic and environmental factors. Despite wide investigations, the role of chronic exposure to environmental pollutants is still rather unknown. Among natural toxins, the mycotoxins have received major attention only in the last few years, due t...

Objective: Swallowing difficulties cause patients with amyotrophic lateral sclerosis (ALS) to crush oral medications, falling outside the labeling instructions and entailing some risks. To date, there is no evidence about consequences of crushing riluzole tablets in a home setting. This simulation experiment evaluated the loss of powder and active...

Background Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients’ residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. Methods Data from the PARALS register were used....

Background: Systemic inflammation has been proposed as a relevant mechanism in amyotrophic lateral sclerosis (ALS). Still, comprehensive data on ALS patients' innate and adaptive immune responses and their effect on the clinical phenotype are lacking. Here, we investigate systemic immunity in a population-based ALS cohort using readily available h...

Introduction/aims: Several microgeographic clusters of higher/lower incidence of amyotrophic lateral sclerosis (ALS) have been identified worldwide. Differences in the distribution of local factors were proposed to explain the excess ALS risk, whereas the contribution of known genetic/epigenetic factors remains unclear. The aim is to identify rest...

The extremely low prevalence of rare diseases exacerbates many of the typical challenges to prognostic model development, resulting, at the same time, in low data availability and difficulties in procuring additional data due to, e.g., privacy concerns over the risk of patient reidentification. Yet, developing prognostic models with possibly limite...

Background Non-invasive mechanical ventilation (NIMV) improves Amyotrophic Lateral Sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking. Objective To test whether NIMV use changed the rate of functional decline among ALS patients. Methods In this retrospective observational study, we...

Objective: To determine the target population and optimize the study design of the phase 3 clinical trial evaluating reldesemtiv in participants with amyotrophic lateral sclerosis (ALS).Methods: We evaluated the phase 2 study of reldesemtiv, FORTITUDE-ALS, to inform eligibility criteria and design features that would increase trial efficiency and r...

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carb...

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative condition. Despite significant advances in pre-clinical models that enhance understanding of disease pathobiology, translation of candidate drugs to effective human therapies has been disappointing. There is increasing recognition of the need for a precision medicine approach tow...

Objective Despite recent advances, it is not clear whether the various genes/genetic variants related to ALS interact in modifying patients phenotype. The aim of this study was to determine if the co-presence of genetic variants related to ALS has interactive effects on the course of the disease. Methods The study population includes 1,245 ALS pat...

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequenc...

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive loss of motor neurons in the brain and spinal cord. The fact that ALS's disease course is highly heterogeneous, and its determinants not fully known, combined with ALS's relatively low prevalence, renders the successful applicatio...

In preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells (Tregs), and autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Rapamycin has never been tested in ALS patients. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigne...

Recent advances in sequencing technologies and collaborative efforts have led to substantial progress in identifying the genetic causes of amyotrophic lateral sclerosis (ALS). This momentum has, in turn, fostered the development of putative molecular therapies. In this Review, we outline the current genetic knowledge, emphasizing recent discoveries...

Aims To estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS. Materials and methods We performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-rang...

(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help with defining patients’ prognoses and stratifications. Besides neurofilaments, chitinases are a promising family of possible biomarkers which correlate with neuroinflammatory status. We evaluated the plasmatic levels of CHI3L1 in MNDs, MND mimic...

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS) are chronic diseases characterized by progressive or alternate impairment of neurological functions (motor, sensory, visual, cognitive). Patients have to manage alternated periods in hospital with care at home, experiencing a constant uncertainty regarding the timing of the disease acu...

Humans are thought to be more susceptible to neurodegeneration than equivalently-aged primates. It is not known whether this vulnerability is specific to anatomically-modern humans or shared with other hominids. The contribution of introgressed Neanderthal DNA to neurodegenerative disorders remains uncertain. It is also unclear how common variants...