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
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.