IInhibitors of TTBK1 for the Treatment of Neurodegenerative Diseases

Compounds that inhibit tau and tubulin kinase (TTBK1) for use in the treatment and/or prevention of neurodegenerative diseases in which this enzyme is involved.

Market need: Neurodegenerative diseases associated with the pathological aggregation of tau and TDP‑43 in the human brain affect millions of people worldwide and represent a growing burden on healthcare systems due to population ageing. Tau and tubulin kinases (TTBK) are involved in the phosphorylation of tau, tubulin, and TDP‑43 substrates, and therefore play a key role in the development of tauopathies and/or TDP‑43 proteinopathies.
Inhibition of the TTBK1 isoform, which acts at early stages of the neurodegenerative cascade, represents an innovative therapeutic strategy with disease‑modifying potential.

Proposed solution: This technology comprises a family of compounds capable of selectively inhibiting the TTBK1 enzyme and crossing the blood–brain barrier, representing a major advance in the treatment of neurodegenerative diseases such as tauopathies and TDP‑43 proteinopathies.
The potential applications include, but are not limited to: amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alexander disease, Perry syndrome, hippocampal sclerosis, traumatic brain injury, Alzheimer’s disease

Competitive advantages

They are permeable to the blood–brain barrier (BBB).
They act as selective inhibitors of TTBK1 and do not inhibit TTBK2, an isoform involved in vital cellular processes.
Strong potential as drug candidates for central nervous system diseases characterized by hyperphosphorylation of tau and TDP‑43 proteins