Seiko Ikezu, M.D.

Location

Contact

SUMMARY

The research interests of Seiko Ikezu, M.D., include exploring therapeutic interventions to delay tau pathology development during the early stage of Alzheimer's disease. One of these therapeutic targets is tau-tubulin kinase 1 (TTBK1). This central nervous system-specific tau kinase enhances tau phosphorylation in the entorhinal cortex where early tau pathology evolves. Another target is microglial tumor susceptibility gene 101, the key molecule for extracellular vesicle synthesis, which may facilitate propagation of aggregated tau protein in aging brains.

Another scope of Dr. Ikezu's research is investigating microglial involvement in the pathogenesis of autistic spectrum disorders. Her recent study involved rejuvenating microglia, innate immune cells in the central nervous system, using a colony-stimulating factor 1 receptor inhibitor. Results from this study suggest this process may have a therapeutic effect on autistic-like behaviors observed with a maternal immune activation mouse model.

Focus areas

• Antisense oligonucleotides (ASOs) targeting TTBK1 as a therapy for early Alzheimer's disease. Dr. Ikezu's team is developing a therapeutic modality using ASOs targeting TTBK1 to slow the progression of Alzheimer's disease. TTBK1, a tau kinase specifically expressed in the central nervous system, enhances tau phosphorylation and axonal degeneration, which are the hallmarks of Alzheimer's disease pathology. In collaboration with Ionis Pharmaceuticals Inc., the team will test ASO-TTBK1 using a mouse model as well as frontotemporal lobar degeneration using human-derived induced pluripotent stem cell (iPSC) neurons to determine the therapeutic efficacy of silencing TTBK1 in Alzheimer's pathology.
• ASOs targeting microglia-specific tumor susceptibility gene 101 as a therapy for Alzheimer's disease. Dr. Ikezu's team will develop a method for targeting microglia-specific molecules using ASO in collaboration with Ionis and a research team led by Debabrata (Dev) Mukhopadhyay, Ph.D., at Mayo Clinic in Florida. Tumor susceptibility gene 101 is one of the major molecules used to facilitate the synthesis of extracellular vesicles. These vesicles are believed to disseminate pathological proteins including aggregated tau as vehicles in Alzheimer's disease.
• Microglial neuritogenic factors as key players in autistic spectrum disorders pathogenesis. Dr. Ikezu's team recently found the novel pathological mechanism mediated by immune-perturbed offspring microglia during pregnancy in autistic spectrum disorders. They will focus on the long-lasting microglial phenotypic change related to early immune insult and its effect on cognitive function in patients with autism.

Significance to patient care

Dr. Ikezu's research can help the development of future for Alzheimer's disease or autistic spectrum disorders by uniquely focusing on central nervous system-specific tau kinase or microglia.

Professional highlights

• Research topic editor, "New Insights into Brain Aging and Autistic Spectrum Disorders," Neurocognitive Aging and Behavior section, Frontiers in Aging Neuroscience, 2022.
• Alzheimer's Disease Center Career Development Award, Boston University, 2018-2019.