Endowed Chair

Precision Medicine for Dementia

Evolving from intuitive medicine to precision medicine
  • Classifying Alzheimer’s disease by the onset molecular mechanism
  • Development of blood biomarkers for dementia
  • Translation of mouse models to study complex human diseases
  • Use of genome editing technologies to study brain-related pathologies
  • Investigating RNA splicing in brain-related diseases

Incorporating instrumentation engineering into basic and clinical research on dementia

Despite its first diagnosis in 1906, there is little in the way of treatment for Alzheimer’s disease. The reason is the complexity and variability of the disease, which besides new medicines has also prevented the discovery of effective biomarkers. Our aim is to integrate different tools that will allow us to study the pathology and uncover new biomarkers of the disease.

        Fig.1 Challenges in studying Alzheimer’s disease.

Accurate diagnostics

We are seeking biomarkers that will not only enhance the quality of diagnosis, but also make it easier for non-specialists to recognize the disease.

Innovative treatments

The absence of effective biomarkers has made it difficult to classify patients in clinical trials and hindered drug development. Blood biomarkers would therefore contribute immeasurably to innovative treatments for dementia.

Precision Medicine

It is thought that there are multiple causes for Alzheimer’s disease, and these causes are expected to affect treatment strategies. Indeed, patients can be stratified into subgroups based on the disease status and molecular factors1,4, which can be measured by blood biomarkers. These subgroups are more homogeneous with one another as compared with the whole population of Alzheimer’s patients, suggesting they are more likely to benefit from a common therapy. The subgrouping of patients and the application of a corresponding therapy is known as precision medicine, which has been shown effective for treating cancer patients. Furthermore, precision medicine is expected to lower medical costs.

        Fig.2 Outline of precision medicine. Left:It is difficult to develop one effective therapy for a group of Alzheimer’s disease patients for which different onset factors cause the disease. Right:By subgrouping patients by the onset factors, the likelihood of finding an effective treatment increases.

Bringing instrumentational engineering to basic and clinical research

The development of blood biomarkers and precision medicine for dementia will benefit greatly from not only clinical and basic research, but also through the incorporation of quantitative techniques to the field. We are fortunate to have an abundance of clinical specimens at Osaka University Graduate School of Medicine Department of Psychiatry. We have also established a course for dementia to train future researchers and a collaboration with MagQu, which has provided their immunomagenetic reduction technology as a novel quantitative measurement tool.

A colleague of ours, Prof. Takashi Morihara, and his research team have identified Klc1 as a causative gene in mouse models of Alzheimer’s disease. Following this discovery, we elucidated the onset mechanism by studying and have found corresponding biomarkers1. In addition, following work by Dr. Kenichi Nagata, we are using CRISPR-Cas technology to clarify the onset mechanism of Alzheimer’s disease further 2,3. At the same time, abnormal RNA splicing is also found in patients and is suggested to contribute to the disease. Finally, in combination with our KLC1 studies, we are also using instrumentational engineering to examine the onset mechanism.

Our expectation is that this approach will significantly contribute to new precision medicine.

References

1. Morihara T et al. Proc Natl Acad Sci U S A 111, 2638-43, 2014.
2. Nagata K et al. Nat Commun ;9, 1800, 2018.
3. Sasaguri H, Nagata K et.al. Nat Commun. 9, 2892, 2018.
4. Yamaguchi-Kabata Y et al. Hum Genet. 137, 521, 2018.