Translation of regenerative neurological therapies
Common themes of inflammation, oxidative stress, mitochondrial dysfunction and protein mishandling recur across multiple neurological diseases. To date, therapeutic strategies targeting unique features of individual diseases studied in animal models have proved unsuccessful in clinical trials.
To identify recurrent themes across human neurological diseases, Dr. Burns and colleagues took an alternate approach, performing a rigorous transcriptional meta-analysis of available human data for Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis, thereby defining the conserved transcriptional signature of human neurodegeneration.
Comparison of this human signature to that of neurodegenerative animal models revealed striking differences. These data help explain why therapies that appear promising in animal models of neurodegeneration have rarely succeeded in human clinical trials. This work helps provide a path forward in developing innovative translational pipelines that yield therapies that work in humans rather than mice.
- Li MD, Burns TC, Morgan AA, Khatri P. Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases. Acta Neuropathologica Commununications. 2014; doi:10.1186/s40478-014-0093-y.
- Burns TC, Li MD, Mehta S, Awad AJ, Morgan AA. Mouse models rarely mimic the transcriptome of human neurodegenerative diseases: A systematic bioinformatics-based critique of preclinical models. European Journal of Pharmacology. 2015; doi:10.1016/j.ejphar.2015.03.021.
- Burns TC, Li MD, Mehta S, Awad AJ, Morgan AA. From mice to mind: Strategies and progress in translating neuroregeneration. European Journal of Pharmacology. 2015; doi:10.1016/j.ejphar.2015.03.041.