Expression Profile Study of Macrophages From Patients Affected by ALS or Other Related Motor Impairments (Mac2ALS)

Expression Profile Study of Macrophages From Patients Affected by Amyotrophic Lateral Sclerosis (ALS) or Other Related Motor Impairments

The aim of this project is to analyze the macrophage transcriptome and protein markers of Amyotrophic Lateral Sclerosis (ALS) patients compared to controls (non-affected individuals, patients with other motor impairments) and asymptomatic ALS gene carriers, to find new pathways for therapeutic targets and disease biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis

Detailed Description

Amyotrophic Lateral Sclerosis (ALS) is the most common motor neuron disease in adults affecting upper and lower motor neurons resulting in progressive muscle atrophy and paralysis of the patients within 2 to 5 years. The majority of ALS cases are sporadic (SALS), 5 to 10% are familial forms (FALS). In France, the most frequent mutation is an intronic hexanucleotide expansion in the C9orf72 gene, representing 46% of FALS followed by mutations in the first discovered ALS gene, SOD1 accounting for around 10% of FALS. Using mutant SOD1 ALS mouse models, the investigators and others have shown that motor neurons degenerated through a non-cell autonomous mechanism involving microglial cells. Microglial cells are the macrophages of the central nervous system (CNS) capable of producing neurotrophic or neurotoxic factors. Microglial cells are part of the myeloid lineage like macrophages at the periphery, however these two cell types have different developmental origins and are in different environments. Spinal motor neurons are particular neurons since their cell body is in the CNS, and therefore surrounded by microglial cells, while their axon extends at the periphery and is therefore in contact with peripheral macrophages. The investigators have shown that (i) peripheral macrophages in affected peripheral nerves of ALS mouse models and ALS patient post-mortem tissues were activated, (ii) in ALS mouse models, both microglial cells but also peripheral macrophages participated in disease progression and (iii) peripheral macrophages were able to influence microglial cell reactivity.

The working hypothesis is that peripheral macrophages are themselves (and not just microglial cells) involved in ALS and with this project the investigators want to compare macrophages from ALS patients and controls using macrophages derived from blood monocytes. The aim is to analyze the macrophage transcriptome and protein markers of Amyotrophic Lateral Sclerosis (ALS) patients compared to controls (non-affected individuals, patients with other motor impairments) and asymptomatic ALS gene carriers, to find new pathways to target and disease biomarkers.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: François SALACHAS, MD; Phone Number: +331 42 16 24 72; Email: nathalie.cormand@aphp.fr
• Study Contact Backup: Name: Severine BOILLEE, PhD

Study Locations

• France
  • Paris, France, 75013
    • Recruiting
    • Département de Neurologie, Hôpital de la Pitié-Salpêtrière
    • Contact: François Salachas, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Group 1: Be affected by Amyotrophic Lateral Sclerosis (ALS) definite, probable or possible (El Escorial criteria) sporadic SALS (no known history in the family) or familial FALS (at least one other member of the family affected)

Group 2: Be a carrier of a known mutation causing ALS and be asymptomatic

Group 3: Have a motor impairment related to ALS including the following pathologies: Motor neuropathy, myopathy, Myositis, Spastic paraplegia, Cram / fasciculation syndrome, Chronic inflammatory polyradiculitis, somatization disorder, Anterior spinal artery syndrome, encephalitis, myelitis, Peroneal neuropathy, cervical myelopathy with radiculopathy, spinocerebellar ataxia, Kennedy disease, Spinal atrophy, Hereditary distal motor neuropathy.

Group 4: Healthy control

Description

Inclusion Criteria:

• Agree to participate in this research and have signed an informed consent
• Be able to understand the objectives and procedures of the study
• Be affiliated to French social security or equivalent

• Meet one of the criteria below:

  (i) Be affected by Amyotrophic Lateral Sclerosis (ALS) definite, probable or possible (El Escorial criteria) sporadic SALS (no known history in the family) or familial FALS (at least one other member of the family affected), (ii) not being affected by ALS but having a close relative who has or has been diagnosed with ALS and has or is a carrier of a known mutation causing ALS and has consented to a genetic analysis, (iii) Have a motor impairment including the following pathologies: Motor neuropathy, myopathy, Myositis, Spastic paraplegia, Cram / fasciculation syndrome, Chronic inflammatory polyradiculitis, somatization disorder, Anterior spinal artery syndrome, encephalitis, myelitis, Peroneal neuropathy, cervical myelopathy with radiculopathy, spinocerebellar ataxia, Kennedy disease, Spinal atrophy, Hereditary distal motor neuropathy.

(iv) be accompanying a person with ALS or other motor impairment that is followed by one of the doctors from the ALS referral center at the Pitié-Salpêtrière hospital or by a neurologist from the neurophysiology department at the Pitié-Salpêtrière hospital.

Exclusion Criteria:

• Be subjected to a legal protection measure (safeguard of justice, curatorship or guardianship)
• Refusing to participate in the study
• Whose condition, in the opinion of the doctor, is incompatible with blood draw or participation in research
• Being pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Amyotrophic Lateral Sclerosis (ALS); Blood draw
asymptomatic carriers of ALS mutations; Blood draw
patients with motor impairment other than ALS; Blood draw
healthy controls; Blood draw

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of transcriptome differences between the ALS group and the 3 other groups of participants.	Will be considered different modulation superior or equal to 1.5 fold with a statistical value of p<0.05.	5 years

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Study Director: François SALACHAS, MD, APHP, Hôpital de la Salpêtrière, INSERM U1127, ICM

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2021
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: March 19, 2021
• First Submitted That Met QC Criteria: March 24, 2021
• First Posted (Actual): March 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: C20-55; 2020-A03348-31 (Registry Identifier: ID RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No