Identification of Early Markers for ALS

Institut National de la Santé Et de la Recherche Médicale, France60 enrolled

Overview

Although several molecules have been proposed as biomarker candidates, a clinically established signature for an early or even premotor diagnosis of ALS is not available. Due to the already advanced, disease stage at the time of diagnosis as well as rapid disease progression, an early diagnosis is mandatory for efficacious disease-modifying therapies. In this project, the investigators will develop a clinical molecular fingerprint of PGMC that will provide insight into the molecular pathogenesis of ALS and allow earlier diagnosis.

Study Type

INTERVENTIONAL

Allocation

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Interventions

lumbar puncture

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: FIRST GROUP: Premotor gene mutation carriers (PGMC): * 18-90 years of age * Provision of a written informed consent * Affiliation with a social security scheme or beneficiary of such a scheme * Diagnosed by a clinically certified laboratory with a disease- causing mutation in a known ALS gene by predictive genetic testing * No symptoms of motor neuron disease explainable otherwise than by mutation in a known ALS gene SECOND GROUP: Control subjects to premotor gene mutation carriers (CTR): * 18-90 years of age * Provision of a written informed consent * Affiliation with a social security scheme or beneficiary of such a scheme * No known genetic mutation and no known ALS disease in close family * No diagnosed motor-neuron disease THIRD GROUP: ALS (EALS) / ALS mimics (MIM) * 18-90 years of age * provision of a written informed consent * affiliation with a social security scheme or beneficiary of such a scheme * Patients with pure motor symptom or early ALS (EALS) or ALS mimics (MIM) EALS are patients with pure motor symptom / early motor symptoms of ALS, including those, where the diagnosis of ALS can already be made. These may be patients who meet the following criteria: According to El Escorial criteria : patients who can be classified as possible ALS or those who show upper motor neuron (UMN) signs only or lower motor neuron (LMN) signs only, so that classification as possible ALS is also not possible. Symptoms should not persist for more than 12 months. According to Gold Coast criteria: Patients who do not fulfill the criterion of temporal progression or patients who only show UMN signs or only LMN signs in one region and thus do not fulfill the diagnostic criteria of ALS. Exclusion Criteria: * Inability to express consent to the study * Persons subject to a judicial safeguard measure, under guardianship or curatorship. * Linguistic incapacity or psychic refusal to read the information. * Pregnant women * Foreseen inability to attend scheduled visits * Persons refusing to take one of the following samples: Acquisition of blood samples, Acquisition of tear fluid samples, Acquisition of urine sample

Outcomes

Primary Outcomes

Differential proteome from plasma, tear fluid, Cerebrospinal fluid

Proteome (DIA-MS) from plasma, tear fluid and cerebrospinal fluid in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics

Time frame: Baseline, 1 year

Differential metabolome from plasma, urine , Cerebrospinal fluid

Metabolome (LC-MS/MS) from plasma, Urine and cerebrospinal fluid in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics

Time frame: Baseline, 1 year

Nf-L, tau/phospho-tau, GFAP (SIMOA) from plasma and CSF

Nf-L (Neurofilament light protein), tau/phospho-tau, GFAP from plasma and CSF in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics. By SIMOA technology

Time frame: Baseline, 1 year

Soluble p75ECD (ELISA) from urine

Soluble p75ECD (ELISA) from urine in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics.

Time frame: Baseline, 1 year

B-SIT score (0-12 pts.)

Brief Smell Identification Test B-SIT score (0-12 pts.) in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics.

Time frame: Baseline, 1 year

Questionnaire

Complete a Questionnaire with health data In Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics.

Time frame: Baseline, 1 year

ECAS-score

Cognitive assesment Edinburgh Cognitive and Behavioural ALS Screen-score In Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics.

Time frame: Baseline, 1 year

Standardized neurological examination by ALSFRS-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale)

ALSFRS is an instrument for evaluating the functional status of patients with Amyotrophic Lateral Sclerosis.Neurological. Assessment in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics. Minimum score 0, maximum score 40

Time frame: Baseline, 1 year

Standardized neurological examination by Manual Muscle Testing (MMT)

Manual Muscle Testing provides helpful information about muscle quality. Grade 0 : no concentration palpable to Grade 5 : normal strength. Assessment in Premotor gene mutation carriers vs. Control group and Early ALS vs. ALS Mimics.

Time frame: Baseline, 1 year

Identification of Early Markers for ALS

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Central Contacts