NCT01992029

Study of miRNA Expression Pattern as Diagnostic and Prognostic Biomarker in Amyotrophic Lateral Sclerosis

Etude de l'Expression Des Micro-RNA Comme Biomarqueur Diagnostic et Pronostic Dans la Sclérose Latérale Amyotrophique

• Status: Terminated
• Phase: —
• Study type: Observational
• Enrollment: 5 (actual)
• Sponsor: University Hospital, Bordeaux · Academic / Other
• Sex: All
• Age: 45 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The principal goal is to demonstrate that a specific pattern of microRNA (miRNA) expression can be correlated with the definite diagnostic of Amyotrophic Lateral Sclerosis (ALS). The investigators will use biological sample (from muscle biopsy, Cerebrospinal Fluid (CSF) and blood sample) collected in three control populations: definite ALS patients according to El Escorial diagnostic criterion, control patients without any neurological disease having an orthopedic surgery for shoulder disease, and control patient explored for peripheral neuropathy and myopathy. A second goal will correlate the miRNA pattern to the severity and/or progression rate of the motor neurons define as the progression rate of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) score/year.

Detailed description

Amyotrophic Lateral Sclerosis is an adult-onset neuro degenerative disease leading to muscle wasting, palsy and death due to respiratory failure within 3 to 5 years. The only effective drug (Riluzole) increases the life expectancy for about three months, knowing that on average, the diagnostic is given after a delay of one year in France. The identification of new biomarkers for early diagnostic is therefore of fundamental importance. This could improve the treatment efficacy but also give important clues about the prognostic, the rate of evolution and overall help identify new targets for future therapeutics. The investigators' goals are to find specific miRNA patterns expression associated to ALS in humans and use those patterns as diagnostic and prognostic tools. miRNA are non-coding small fragments of RNA that binds mRNA and can down regulate their expression. In humans, around 700 miRNA have been so far identified. The role of miRNA in human pathology is well established in various types of cancer, but recent works have emphasize their role in neuro degenerative diseases and their expression profile can considered specific for Alzheimer, Parkinson and Huntington diseases. Very few data are currently available about their expression pattern in ALS. Previous studies have however shown that down regulating of some miRNA in spinal cord Moto neurons can trigger an ALS-like clinical phenotype. A more recent work on transgenic murine model SOD1 G93A has demonstrated the role of the specific miRNA206 in regulating the re-innervation processes at the neuro-muscular junction. Mi206 have the ability to promote the re-innervation process and therefore to slow the disease progression. This research aimed to study the expression of more than 700 miRNA in four different groups (20 patients per group): ALS patients, normal control having a shoulder surgery during which they will have a muscle (deltoid) biopsy, patients explored for peripheral neuropathy with a blood sample, a lumbar puncture for CSF examination and neuro-muscular biopsy and patient explored for myopathy with a blood sample, a lumbar puncture for CSF examination and a muscular biopsy. The ALS group will be followed up every 4 months with ALSFRS scoring and blood sample and a second CSF sample only at M12. miRNA pattern expression will be compared and considered significant for a 2-fold change.

Conditions

• Amyotrophic Lateral Sclerosis
• ALS

Interventions

Type	Name	Description
OTHER	Clinical evaluation	Clinical evaluation using MRC scale, Norris bulbar scale, ALSFRS score and respiratory evaluation ( Vital Capacity, PiMax and SNIP) at M0, M4, M8, M12
PROCEDURE	Muscular biopsy	Muscular biopsy at M0
PROCEDURE	Lumbar puncture	Lumbar puncture at M0 and M12
PROCEDURE	Blood sampling	Blood sampling at M0, M4, M4, M8 and M12
OTHER	Neurological assessments	Neurological assessments (MRC score and cognitive scales: MMS and BREF)
PROCEDURE	Neuro-muscular biopsy and lumbar puncture	Neuro-muscular biopsy and lumbar puncture for patients explored for peripheral neuropathy
PROCEDURE	Muscular biopsy	Muscular biopsy for patient explored for myopathy
PROCEDURE	Blood sample	Blood sample for qRT PCR, detection and quantification for miRNA
DEVICE	Cervical spinal cord and brain MRI	ALS patients : MRI at inclusion and Month 8 Control patients suffering from neuropathy : MRI at inclusion and Month 8 Control patients suffering from myopathy : MRI at inclusion Control subjects : MRI at inclusion

Timeline

• Start date: 2014-06-17
• Primary completion: 2015-10-01
• Completion: 2015-10-22
• First posted: 2013-11-25
• Last updated: 2018-11-05

Locations

1 site across 1 country: France