Our strategies

The following are what we do at RIKEN BIO Co. Ltd., Tokyo, JAPAN.

As we discuss later, the entire pharmaceutical community appears moving into wrong directions. This is not only an industrial matter because so much of tax payers’ money (billions of dollars) is being used for longitudinal prevention studies (API, DIAN and A4). A number of pharmaceutical companies will disappear from the earth if these trials fail. We would like to contribute to validation and improvement of the on-going R & D processes.

  1. Licensing the next-generation mouse models of AD: The 1st generation mouse models of AD that have been developed since 1995 suffer from artificial phenotypes because of the super overexpression of APP, and thus have failed to constitute appropriate platforms for understanding the pathological mechanisms and for validating candidate medications. To overcome these drawbacks, we generated App knock-in mice that accumulate Aβ42 without overexpressing APP (Nat Neurosci, 2014). These mice have already been used by a number of renowned AD researchers all over the world and will soon become a world standard, replacing existing models. We will license the new mouse models to for-profit organizations by a contract. Right now, RIKEN provides non-profit organizations with the mutant mice free of charge under an MTA (Material Transfer Agreement), which requires the following. [1] Recipients must reveal the research plan(s) to providers and cannot use the mice for any other purpose. [2] Recipients must report the research results to providers. [3] Recipients must coauthor providers in publications. [4] If recipients obtain any result(s) that may be considered as an IP (intellectual property), the IP must be shared by both sides. [5] Recipients must not provide any 3rd party with the mutant mice under any conditions. An academic license contract with RIKEN BIO Co. Ltd. will exempt items from [1] to [4] described above. We will provide users with all the information that we have about biochemical, histochemical and behavioral analyses of the models. Academic prices will apply to non-profit organizations. Please contact CEO (saido@rikenbio.com) for details. For your reference and interest, please see a list of some of the top scientists using our mouse models.

  2. Clinical application of gene therapy to prevention of AD: We previously identified the major Aβ-degrading enzyme, neprilysin, for the first time in the world (Nat Med, 2000; Science, 2001). Next, we succeeded in generating a gene therapy by injecting a viral vector into the brain of model mice (J. Neurosci., 2004). We then developed a new vector that can deliver neprilysin cDNA from periphery to brain (Sci. Rep., 2013). We are conducting a preclinical study using aged non-human primates to confirm the safety of gene therapy. This approach allows stable expression of neprilysin in the brain for more than 10 years without damaging the host genome. We collaborate with Professor Muramatsu, Jichi Medical College. We expect the gene therapy to exert drastic preventive effects on presymptomatic familial Alzheimer’s disease mutation carriers.

  3. Medications for prevention of AD: We previously discovered that a neuropeptide, somatostatin, activates neuronal neprilysin (Nat Med, 2005). Somatostatin receptors belong to the G protein-coupled receptor family and thus serve as an ideal target for low molecular weight medications. There exist five receptor subtypes for somatostatin: the identity of the receptor subtype responsible for neprilysin activation remains elusive. We are in the process of identification and will synthesize orally administrable agonists, which will provide means to protect people at risk from developing Alzheimer’s disease. Somatostatin receptor agonists may also contribute to controlling pains. We will also utilize the 2nd generation mouse models (Nat Neurosci, 2014) to search for foods and supplements, which would help reduce the risk of developing Alzheimer’s disease.

  4. Plasma-based presymptomatic diagnosis of AD: We have identified plasma biomarker candidates for presymptomatic diagnosis of Alzheimer’s disease using the 2nd generation mouse models (Nat Neurosci, 2014). We will validate the relevance of these candidates by quantifying them in human plasma samples from amyloid PET-positive and negative cognitively normal people. The amyloid PET, used to visualize amyloid deposition in the brain, costs about $3,000 and takes a few hours per person. In contrast, the plasma-based diagnosis would only cost $50 and take a few min, reducing the examinees’ burdens by the factor of 100.

  5. Consultation for  AD research and development: Every year, more than 6,000 papers on Alzheimer’s disease and related disorders are published. Based on the published and unpublished information that we have, we can provide our customers and future investors with the latest knowledge and future perspectives. Please see “A cautionary note on Alzheimer immunotherapy,” for instance. All the major pharmaceutical companies must know this.

  6. Non-human primate models of AD: We plan to generate non-human primate models of Alzheimer’s disease in collaboration with Central Institute for Experimental Animals and Keio University. The models will be used for preclinical trials of medication candidates and shall contribute to reducing the costs for clinical trials with humans. We will eventually build an animal facility in Japan or in one of the Asian countries for preclinical studies of medication candidates, which are difficult to perform in Western countries.

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Amyloidosis in model mouse

Amyloidosis in our mouse model of AD