AMED missions start with IRUD: Initiative on Rare and Undiagnosed Diseases – Challenge to overcome Balkanization
Makoto Suematsu, President, Japan Agency for Medical Research and Development AMED: “The situation in Japan is so crazy, but now I will stay in Japan because I have a mission”
Our goal is to fast-track medical R&D that directly benefits people not only by extending life, but also by improving quality of life.
Supporting research in “three different concepts of life”:
- life sciences
- daily life
- quality of life
AMED works with three Japanese Government Ministries: METI & MEXT & MHLW
AMED total budget in FY2015 is US$ 1.4 billion.
The challenge is to combine the efforts of these three Ministries which all have different rules and requirements. It is our job at AMED to overcome this “balkanization” between Ministries, as pointed out by Denis Normile’s article: “Japan’s ‘NIH’ starts with modest funding but high ambitions”, SCIENCE, 348, Issue 6235, pp 616, DOI: 10.1126/science.348.6235.616
Starting with (1) rare diseases and (2) cancer
We are using a matrix approach and start with (1) rare diseases and (2) cancer to trial our approach to optimize medical R&D.
On one axis of the matrix we have:
- Drug research
- Regenerative medicine research
- Cancer research
- Neurological, psychiatric and brain research
- Rare/intractable disease research
- Emerging research
On the other axis of the matrix we have:
- Industrial-academic collaboration: support for practical applications such as industrial-academic collaboration
- International affairs: promotion of strategic international research
- Genome research and infrastructure: support for accommodating R&D platforms such as BioBank etc
- Clinical research and trials: support for high-quality clinical studies/clinical trials
- Innovative drug discovery and development: support through the Drug Discovery Support Network for realizing drug discovery in academia
Why did we start from Rare & Undiagnosed Diseases (IRUD) in 2015?
- Our aim is to support medical research considering three different types of life
- Life science
- Daily life
- Quality of life
- Stop “research for budgets”, empower “budgets for research”
- Global data sharing (overcoming researchers’ “biological behavior”)
- Diversity of diseases causes fragmental budgets, centralization of expensive analyzing machines
- Establishing new matrices to check the quality of projects
- Farewell to “Darth Vader-type research”, patients should be covered by network-type systems
- Not only diagnosis, but also drug discovery for R and C (attracting great interest by Megapharma for orphan drugs)
Globally shared “death valley”
- University vs Medical School & Hospital
- Patients’ need vs physicians’ desire
- Sequencer vs physicians
- Scientists vs bureaucrats
- Bureaucrats vs bureaucrats
- University vs industry
- University vs university
- Medicine vs other sciences
SWAN = Syndrome without a name, leading to a diagnostic odyssey
BBC reports on the case of Jessica Hawley, and her and her family’s suffering under a “Syndrome Without A Name” (SWAN).
Lauren Roberts, of SWAN UK says:
“You have no idea what the future holds for a child. If you don’t have a diagnosis, you don’t know if they’ll ever walk, or talk, or what their life expectancy might be. You spend your whole life going through this constant emotional rollercoaster of test after test coming back negative and no-one being able to give you any answers. They can have their entire genetic code sequenced, but we still can’t find the root of the problem. It’s mainly because it’s such a tiny change in their genetic code that doesn’t get picked up in the tests.”
AMED has launched the Initiative for Rare and Undiagnosed Diseases (IRUD)
We set up IRUD committees at all hub medical institutions building an all-Japan network for IRUD. These IRUD committees build regional alliances bringing together home doctors, IRUD analysis centers for genetic testing, e.g. exome sequencing.
The IRUD committees interact with the IRUD Data Base System for IRUD.
With regional IRUD committees in combination with a central IRUD data base, we can find patients with similar symptoms which might have the same rare disease.
Indeed, MacArthur et al. in “Guidelines for investigating causality of sequence variants in human disease”, Nature 508, 469–476 (24 April 2014) doi:10.1038/nature13127 write:
In order to identify a new disease-causing gene which has been unknown as a disease-causing gene, it is necessary to find out multiple patients who have a combination of similar clinical phenotypes and sequence variants in same gene
To decide on Rare (R) and Undiagnosed (U) diseases, we use a series of filters, including global research on multifactorial genetic disorders, and we use IRUD diagnostic committees including a wide range of specialists, clinical conferences with clinical geneticists, and alliances with home doctors.
Janel Johnson et al in “Exome sequencing reveals riboflavin transporter mutations as a cause of motor neuron disease”, Brain, 2012 Sep; 135(9): 2875–2882, doi:10.1093/brain/aws161 showed that precise genome diagnosis can identify treatable variants of genetic diseases.
Via AMED, Japan joined the International Rare Diseases Research Consortium (IRDiRC) from July 30, 2015:
- data sharing for patients
- global coding of phenotypes
- micro attribution
- machine-readable consent
- harmonized IRB
On January 11, 2016, a Memorandum of Cooperation was signed between NIH and AMED in the guest all of the US National Academy of Science:
- empowering historical collaboration in infectious diseases and surveillance
- overcoming dementia through strong basic science and brain initiatives
- data sharing in rare and undiagnosed diseases
As an example, it was possible to identify patients with corresponding rare genetic diseases both in the USA and Japan.
AMED: Perspectives for fast-track medical R&D to improve global quality of life
- Eliminate obstacles of inflexible funding systems caused by “Balkanism” (conflicts of different funding systems by different agencies). AMED has completed de reform of funding rules on January 13, 2016
- Help ARO network to fully utilize a flexibel funding system
- “Making a little leak will sink a huge old ship”. Start from IRUD:
- Data sharing
- Global phenotype coding
- Central IRB (pilot)
- Collaboration with IRDiRC, UDN (NIH) from FY2015
- Global alliance for IRUD data sharing and infection surveillance
- Activate basic research to foster young “masters” in Japan through activating global collaboration. AMED global partnership: Gero-sciences, structural biology, mass spectrometry, metabolomics, etc.
- improve the quality of big data science to evaluate clinical research (eg NCD, JANIS etc)
- ONLINE, and IN ENGLISH for Japanese funding systems
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