In a recent study entitled “Complex Inflammation mRNA-Related Response in ALS is Region Dependent” characterizes the inflammatory response in patients with Amyotrophic lateral sclerosis (ALS)” published in the journal Neural Plasticity, a research team led by Isidre Ferrer from the L’Hospitalet de Llobregat in Spain detected alterations of inflammatory factors in the spinal cords and brains of ALS patients.
ALS, also known as Lou Gehrig’s disease or motor neuron disease, is a progressive neurodegenerative disorder caused by the death of upper (brain cortex) and lower (brain stem and spinal cord) motor neurons. ALS patients have muscle weakness and atrophy ultimately losing the ability to initiate and control all voluntary movement. About 30-40% of patients also show a significant cognitive impairment.
Motor neurons of ALS patients accumulate protein aggregates, common to other neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. Inflammatory changes in the Central Nervous System (CNS) are also shared by several neurodegenerative diseases and may contribute to their pathology.
In this study, researchers assessed the specific inflammatory responses in ALS using the same probes as in previous studies of Alzheimer’s disease. Their major goal was to provide a rationale for particular inflammation modulatory therapies in the different disorders. The team studied ALS patients’ brain and spinal cord tissue samples obtained from the Institute of Neuropathology Brain Bank and compared them to control cases.
The results demonstrated increased cellular markers of inflammation in glial cells, astrocytes and microglia in the spinal cord of ALS patients. These cells were producing factors known as pro-inflammatory cytokines such as IL-6 and TNF-a. Another inflammatory factor causing neurodegeneration, IL-1b, was detected in motor neurons of ALS patients. In contrast, a potent anti-inflammatory cytokine, IL-10, was sequestered in protein aggregates suggesting that its potential beneficial effect was lost in ALS patients.
Only ALS patients at terminal stages were studied and therefore information on the inflammatory changes upon disease progression are still lacking. Nevertheless, the authors concluded that this pattern of inflammation is specific for ALS since it differed from those described for Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob’s disease. This study indicates that inflammation related responses are not identical within neurodegenerative diseases with abnormal protein aggregates. Based on these results, the authors suggested that “combined therapies are probably needed to cope with the multiple pathways and variegated molecules that converge in the process of inflammation in ALS”.