Advances in the genetics, pathology and cell biology underlying chronic neurodegenerative disease have identified pathways that trigger neurodegeneration and contribute to disease onset and progression. Denali is applying deep scientific and drug development expertise to fully harvest the potential of these pathways in order to discover effective molecular therapeutics.
Rapid progress in identifying human genetic risk associated with neurodegenerative disease has revealed numerous genes involved in neurodegeneration. Degenogenes, genes that cause neurodegenerative disease when mutated, represent highly validated targets for drug development.
Trafficking of cargo allows cells to efficiently maintain distinct functional domains. The endolysosomal system is involved in the trafficking, digestion, and processing of cellular components. A reduced ability of cells to appropriately direct molecules to and from the endolysosomal system is associated with several neurodegenerative disorders. Therapeutics designed to modulate intracellular trafficking are a promising approach to treat neurodegeneration.
The human brain contains several types of glial cells. These cells serve various functions in the brain, including supporting neuronal health, pruning neuronal synapses, and providing immune surveillance and response. Genetic and pathological data suggest that glial dysfunction significantly contributes to neurodegenerative disease. Correcting glial dysfunction represents an attractive therapeutic strategy.
The functional decline observed in diseases such as Alzheimer’s, Parkinson’s and ALS is caused by the elimination of connections between neurons and the subsequent degeneration of axons. Therapies that block axon degeneration have the potential to halt disease progression.