Abstract
Therapeutic interventions in amyotrophic lateral sclerosis (ALS) are still far from satisfying. Immune modulating procedures raise hopes for slowing the disease progression. Stem cell therapies are believed to possess the ability to regulate innate and adaptive immune response and inflammation processes. Hence, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin–) cells were performed every six weeks in 40 sporadic ALS patients. The concentrations of inflammatory-related proteins and expression profiles of selected miRNA in the cerebrospinal fluid (CSF) and plasma at different timepoints post-transplantation were quantified by multiplex Luminex and qRT-PCR. The global gene expression in nucleated blood cells was assessed using the gene microarray technique. According to the ALS Functional Rating Scale (FRSr), the study population was divided into responders (group I, n = 17) and non-responders (group II, n = 23). A thorough analysis of the pro-inflammatory expression profiles, regulated miRNA pathways, and global gene expression profiles at the RNA level revealed the local and systemic effects of Lin– cell therapy on the immune system of patients with ALS. The autologous application of Lin– cells in CSF modulates immune processes and might prevent the progression of neurodegeneration. However, further in-depth studies are necessary to confirm the findings, and prolonged intervention is needed to maintain therapeutic effects.
Highlights
Immunological processes are known to be implicated in the pathogenesis of multiple neurodegenerative diseases
There were three consecutive applications of autologous cells isolated from the bone marrow of sALS patients, each planned six-week apart
The amyotrophic lateral sclerosis (ALS)-FRSr was chosen as an indicator of clinical response to the cell administration, as it has been previously described that this scale correlates best with the predicted survival time [29]
Summary
Immunological processes are known to be implicated in the pathogenesis of multiple neurodegenerative diseases. Emerging evidence indicates the involvement of immunological pathways in the progression of Alzheimer’s disease, multiple sclerosis, epilepsy, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS) [1]. ALS is a lethal, progressive, neurodegenerative disease that affects the lower and upper motor neurons, leading to the gradual weakening of muscles and death, usually within 3–5 years after the onset of the first symptoms [2]. The most important factors contributing to the loss of motor neurons described until now are increased excitotoxicity resulting from the impaired uptake of glutamate, a dysfunctional blood-brain barrier (BBB), oxidative stress, mitochondrial dysfunction, the accumulation of misfolded proteins, and inflammation on both a local and systemic level [4,5]
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