Sebastian Thams

TL;DR: Reprogramming and stem cell differentiation approaches with genome engineering and RNA sequencing are combined to define the transcriptional and functional changes that are induced in human motor neurons by mutant SOD1, indicating that at least a subset of these changes are more broadly conserved in ALS.

TL;DR: Insight is provided into the mechanisms contributing to the preferential susceptibility of ALS motor neurons, and the utility of stem cell-derived motor neurons for the discovery of new neuroprotective compounds are demonstrated.

TL;DR: It is shown that overexpression of mir-17∼92 significantly rescues human SOD1+/L144F MNs, and intrathecal delivery of adeno-associated virus (AAV)9-mir-17 ∼92 improves motor deficits and survival in S OD1G93A mice, and mir- 17∼ 92 may have value as a prognostic marker of MN degeneration and is a candidate therapeutic target in SOD 1-linked ALS.

TL;DR: Prostetin/12k emerged as an exceptionally potent, metabolically stable, and blood-brain barrier-penetrant compound that is well suited for future testing in animal models of neurodegeneration.