Neuroscience

#1

Research opportunities to generate novel and breakthrough targets for brain disorders

We seek groundbreaking discovery defined by innovation, creativity and/or clinical impact to address promising fundamental therapeutic targets for neurodegenerative and neuropsychiatric disorders*. We prioritize proposals based on human/patient derived approaches (reverse translational research) ideally including one of the following areas:

  • Distinctive therapeutic approaches based on disease mechanism, pathology, or clinical observations (symptoms, imaging, efficacy of drug/non-drug therapies such as non-invasive brain stimulation TMS, etc.)
  • Novel drug targets derived from omics/patient-derived samples (brain/peripheral tissues, bio-fluids, exosomes, miRNA, etc.)
  • Technologies to discover and/or evaluate new targets focusing on synapse biology
  • Unique human disease-relevant pre-clinical models with enhanced translatability for drug discovery
  • Discovery of novel causal mutation (gain-of-function)

* Our focused disease areas:

(1) Neuropsychiatric disorders: mood disorders (treatment-resistant depression, bipolar disorder), schizophrenia (negative symptoms and cognitive impairment), autism spectrum disorder, post-traumatic stress disorder

(2) Neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis

(Modalities: small molecule, peptides, biologics, nucleic acids, others) 



#2

Novel biomarkers for precision medicine in CNS disorders

Patients with neuropsychiatric and neurodegenerative disorders are heterogeneous with various symptoms, pathology, and genetic backgrounds. This heterogeneity is one of the major barriers for drug discovery in CNS disorders* largely affecting the effectiveness as well as side-effects of drug treatment. We seek research proposals addressing novel biomarkers based on human/patient derived approaches (reverse translational research) ideally including one of the following areas:

  • Diagnostic/prognostic/predictive biomarkers for patient stratification
  • Novel biomarkers to better predict brain changes in humans
  • Surrogate markers of efficacy to predict human outcomes with high accuracy that can bridge the gap between human studies and animal models
  • Novel targets with identified biomarkers for a specific patient subpopulation

* Our focused disease areas:

(1) Neuropsychiatric disorders: mood disorders (treatment-resistant depression and bipolar disorder), schizophrenia (negative symptoms and cognitive impairment), autism spectrum disorder, post-traumatic stress disorder

(2) Neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis



#3

Approach to treatment of central nervous system diseases (neurodegenerative diseases, psychiatric disorders) originating from peripheral immunity / inflammation control

Recent studies suggest that peripheral inflammation and immune system abnormalities caused by various mechanisms contribute to the onset and progression of central nervous system diseases.

In this area, we anticipate research ideas aimed at elucidating or modulating the molecular mechanisms leading to abnormalities of peripheral immunity / inflammation involved in disease pathogenesis, as shown in the following examples:

  • Changes in brain infiltration of peripheral immune cells
  • Identification of specific immune cells involved in disease onset / progression and their cell phenotype alterations (cellular senescence, intracellular energy metabolism, exosome production etc.)
  • Dysbiosis



#4

Approach to treatment of central nervous system diseases (neurodegenerative diseases, psychiatric disorders) based on control of crosstalk among nerve cells, immune cells and glial cells

Recent studies suggest that nerve cell dysfunction and death, contributing to the onset and progression of central nervous system diseases, are caused not only by nerve cells themselves but also by glial cells (microglia, astrocyte and oligodendrocyte), and peripheral immune cells such as T cells infiltrating into the brain. It is speculated that the interaction among these cells directly or indirectly affects nerve cells.

In this area, we anticipate research ideas aimed at elucidating or modulating the molecular mechanisms involved in disease pathogenesis through the crosstalk between (1) nerve cells and immune cells, (2) nerve cells and glial cells (except for nerve cells and oligodendrocytes), (3) immune cells and glial cells.



#5

Approach to treatment of central nervous system diseases (neurodegenerative diseases, psychiatric disorders) by immune cell therapy

In this area, we anticipate innovative ideas and technologies for cell therapy using immune cells as a new modality for treating central nervous system diseases as shown in the following examples:

  • Genetically modified cells

           ・CAR-T, CAR-Macrophage

           ・Cells that specifically eliminate autoreactive cells 

           ・Cells with suppressed cellular senescence / exhaustion

           ・Non-plastic cells (maintaining suppressive properties of Tregs)

  • Hematopoietic stem cells
  • In vitro activated cells



#6

Methods to explore drug targets for bipolar disorders caused by mitochondrial dysfunction

There are clinical reports and scientific evidence to indicate that mitochondrial dysfunction causes bipolar disorders, with evidence such as increased mitochondrial respiration and ATP production in the manic phase, and decreased mitochondrial function in the depressive phase. Thus therapeutic drugs focusing on mitochondria are likely to be effective for bipolar disorder; however, no such therapy exists yet. We seek methods for drug target exploration for bipolar disorder caused by mitochondrial dysfunction.



#7

Chemistry-based innovative methods or ideas that would be applicable to basic research on CNS diseases or CNS drug discovery

We seek chemistry-based technologies or ideas for CNS drug discovery.
The following are specific examples. Ideas are not limited to them and are sought from a broad perspective.

  • research on discovery of CNS drugs with novel or/and complex actions such as allosteric modulators, polypharmacological drugs, pharmacological chaperones, protein degradation inducers, RNA modulators, and phenotypic-based drugs
  • research on novel off-target evaluation systems for development of multi-target drugs
  • research on suitable library design (e.g. CNS-focused library, chemogenomic library, etc.) for CNS drug discovery
  • research on "beyond small molecules" to approach CNS disorders and their brain delivery systems
  • drug discovery research on currently undruggable targets involved in CNS diseases, such as phosphatases and ubiquitin-proteasome system
  • research on CNS biomarkers such as novel brain imaging technologies and their chemical probe development
  • CNS drug discovery based on artificial intelligence and machine learning technique
  • research on prevention of neurodegeneration

 



Other Areas of Interest


How to Apply

Follow the procedure below to make an application.

  1. Download the Proposal Sheet below, and complete  based on the non-confidential information.

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  3. Complete the Application Form with your Proposal Sheet prepared at Step1 attached, and click "SUBMIT".

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CONTACT

Please contact the COCKPI-T® Office for further information.

COCKPI-T@takeda.co.jp

  

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