Denali Therapeutics is developing a very wide range of small molecules and other compounds to assist in combating several diseases. Its principal candidate, DNL151, completed Phase 1b human clinical trials as a therapy against Parkinson’s and is planning on moving to late stage clinical trials by the end of 2021 (press release). The goal of this drug is to restore lysosomal function, allowing them to better remove Lewy bodies, which kill vital motor neurons and lead to the symptoms of Parkinson’s. As the lysosomes are responsible for destroying degraded proteins, this therapy directly combats the aging hallmark of proteostasis.

Some of Denali’s other work includes a Phase 1 trial of DNL788, which reduces brain inflammation through inhibiting RIPK1, a Phase 1b trial of DNL343, which is designed to reduce the effects of cellular stress in mutated cells by restoring RNA and protein function, and a Phase 1 trial of DNL310, a brain-penetrant enzyme replacement therapy. Denali is also in early-stage development of a proprietary technology for getting drugs through the blood-brain barrier, and the company is developing further therapies based on this technology.