Introduction

No treatment exists for ALS and the average survival period after diagnosis is approximately 3.5 years. Riluzole is the only conditionally approved ALS medication, but it can prolong the patient life by 2-3 months only. Minocycline is a tetracycline antibiotic which has been used for many years to treat diseases such as acne. The rationale for using this antibiotic for ALS treatment is the fact that an inflammatory response is observed in the nervous system along with degenerescence of motor neurons. In a transgenic mouse model of ALS, minocycline treatment has been shown to prolong life by a few weeks. Phase I and II clinical studies have demonstrated a good tolerance for minocycline medication. Magnetic resonance spectroscopy (MRS) has demonstrated significant brain metabolite variations in ALS patients, especially decreases of N-acetylaspartate (NAA, a neuronal marker) in the motor cortex which correlate with the severity of the disease. Increases of myo-inositol (mI, a glial marker) have also been reported and will be specifically looked at in this study.


Aim

The aim of this project is to study the effect of minocycline treatment on the brain metabolism of 15 ALS patients. Considering the beneficial effect that this drug seems to have, the levels of NAA and mI will be especially monitored for information on neurons and glia, respectively. Measurements will be performed in the motor cortex and brainstem. Variations of other MRS observable metabolites such as choline compounds (Cho), creatine/phosphocreatine (Cr) and glutamine/glutamate (Glx) will also be analyzed. Correlations between MRS and clinical data will be assessed.