Microglial Activation Role In ALS (MARIA)

Microglial Activation Role In ALS (MARIA)

Neuroinflammation, characterized in particular by microglia activation, is an essential component of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Translocator Protein (TSPO) is recognized as a specific and sensitive biomarker of neuroinflammation, reflecting disease activity. An experimental radiopharmaceutical specific of TSPO expression, namely [18F]DPA714, allow to quantify this microglial activation using Positon Emission Tomography (PET) imaging.

The purpose of this study is to longitudinally correlate the spatial distribution of neuroinflammation with the pro- or anti-inflammatory state of activated microglia cells in ALS, in order to evaluate neurotoxic or neuroprotective microglia activity, by complementary approaches in 20 ALS patients:

• in vitro: measuring concentrations of several pro- and anti-inflammatory cytokines secreted by microglial cells in the cerebrospinal fluid (CSF).
• in vivo: [18F]DPA714 PET imaging. These assays will be performed in the framework of the clinical follow-up of ALS patients, at the diagnosis of ALS disease and 6 months latter.

Inclusion Criteria:

• Signed informed consent
• Age ≥ 18 years old
• Patient with probable or definite sporadic Amyotrophic Lateral Sclerosis (ALS) form according to the modified criteria of El Escorial
• Treated with riluzole 2 weeks
• Evolution less than 18 months
• Mini-Mental State Examination (MMS) score ≥ 26 and Frontal Assessment Battery (FAB) (normal)
• Affiliated to a social security system

Exclusion Criteria:

• Another unbalanced progressive pathology

• Vascular diseases (hypertension, diabetes, smoking, dyslipidemia) unbalanced

• Forced vital capacity <75%

• Weight loss> 10% of the weight before disease

• Status "low affinity binder" or "mixed affinity binder", the TSPO respect to the [18 F] DPA-714, which can interfere with the process of neuroinflammation: drugs with anti-inflammatory drugs (NSAIDs, corticosteroids, azathioprine, anti-tumor necrosis factor (TNF), antibiotics)

• Benzodiazepine in the week before the PET scan [18F] DPA-714 given the potential consequences for TSPO receivers

• Contraindications to MRI in patients with:

  1. Metallic foreign body eye.
  2. Any implanted electronic medical irremovably (pacemaker, neurostimulator, cochlear implants ...)
  3. Metal heart valve,
  4. Vascular clips formerly located on cranial aneurysm.

• Treatment in the month before the PET scan [18F] DPA-714 antagonist N-methyl-D-aspartate (NMDA) (memantine)

• Pregnant women, lactating women, and women in age for procreation and without reliable contraception or without history of hysterectomy

• ◦Person under guardianship