Conformational Disease Business

Target the "Misfolding Proteins"

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and Prion disease are known to be caused by the formation and accumulation of misstructured (misfolding) proteins, and these are collectively called “conformational diseases”.
Our company is promoting research and development of both diagnosis and treatment on conformational diseases.

Development of probe for diagnostic imaging

As a diagnostic method for conformational disease, PET (Positron Emission Tomography) is considered to be effective in diagnostic that detects the causative aggregate protein. For example, in Alzheimer's disease (AD), PET probes for detecting amyloid β and tau known as causative aggregate protein have been developed. However, there are many diseases in which the agglutinating proteins have been identified, but many of them has not be developed probes to detect the aggregate protein.

On the other hand, in neurodegenerative diseases, astrocytes one of glial cells increase in the central nervous system. The enzyme "Monoamine oxidase-B (MAO-B)" present in the mitochondrial membrane of the astrocytes is regarded as an index of neuroinflammation or neurodegenerative disease, the index are to say nothing of as an index of diagnosis of AD, we considered that it can also be a diagnostic index of diseases for which other probes have not been developed. And in addition to neurodegenerative diseases, astrocytes are known to also increase in various neurological diseases such as cerebrovascular disorders, traumatic brain injury, and epilepsy. By using MAO-B as a diagnostic index, we expect that early diagnosis of those neurological diseases and understanding of disease states will be possible.

We have so far developed a PET probe "18F-THK5351" that detects both MAO-B and tau for the purpose of diagnosis of AD. With this as the point of start, currently, we are developing PET probes that specifically and selectively detect each of MAO-B and tau. As the PET probes that specifically and selectively detects MAO-B, we have developed "18F-SMBT-1". Currently, exploratory clinical research is underway, and promising data has been obtained. Also, as the PET probes that specifically and selectively detects tau, we have developed "18F-STT-1(tentative name)" and is preparing for towards exploratory clinical research in the near future.
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Image analysis by autoradiography for a part of brain-slice slices with each probe added(image credit: IDAC, Tohoku University)

Development of vaccine treatment

In order to establish a treatment method for conformational diseases, research and development of methods for inhibiting and eliminating protein aggregates has been actively carried out, but it is extremely difficult because the chemical structure of misfolding proteins is not clear.
So in this study, we focused on the seeds that are the core of misfolding protein aggregates. So far, the chemical structure of this seed has not been clarified except that it is an oligomer rich in β-sheet structure, and specific treatment has not been established. In addition, seeds were not recognized as non-self even when inactivated, and the immune response was tolerated and could not be used as a vaccine. In this technology, aiming for to produce specific antibodies for inhibit and eliminate the seed by using seed that cross-linked by applying unique photochemical reaction technology and has inactivateafter that, as a vaccine.
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At present,conducting research with the aim what establishment of active immunotherapy that produces specific antibodies that inhibit or eliminate seed generation by administration of vaccines, and establishment of passive immunotherapy that treats by administering specific antibodies created based on this technology.