ABCtech #90 06-APR-17 Precision Medicine in Japan

ABCtech #90 06-APR-17 Precision Medicine in Japan

Precision medicine is of great interest to readers monitoring emerging and potentially disruptive technologies. Derrick Rancourt is a Professor at the Cumming School of Medicine at the University of Calgary and Director of Biotechnology & Cell Therapies for the Board of the Alberta Council of Technologies Society.  Derrick recently visited Japan to study the status of precision medicine.  He was asked to share with us his findings.  Also included below are both comments received from others familiar with precision medicine and reference to the Alberta’s new stem cell manufacturing laboratory. – Editor

Regenerative Medicine. iPSCs were originally deemed a platform for personalized medicine (i.e. making custom iPSCs to derive patient tissues and organs for transplant). However, Yamanaka, a physician himself, helped put the brakes on this concept by reminding the Japanese healthcare system that personalized medicine would be too expensive to implement in Japan. Instead Yamanaka pushed the concept of precision medicine, by leveraging the fact that Japan has a relatively insular population. He argued that a biobank of 75 human iPSC lines would have a good enough histo-compatibility match to be tolerated by 80% of the population. Reference Based upon this concept Yamanaka has begun to build a team of transplant scientists who are using iPSCs in clinical trials, the first using iPSCs to treat age-related macular degeneration. Reference Based upon the early success of this trial, Japanese regulators have approved the use of the iPSC biobank to treat other patients. Reference This is just the tip of the iceberg, as other clinical trials are in development to treat a variety of age-related degenerative disease in the coming future.

Drug Development. iPSCs can also be made from patients with disease to understand disease etiology and to develop drugs. For example, in collaboration with the Alberta Children’s Hospital, we are generating iPSCs from children who suffer from rare cardiomyopathies. To understand their disease, we differentiate their iPSCs into cardiac tissue in tissue culture, to find out what is wrong and whether drugs can be used to alleviate the disease condition. In Japan, Yamanaka has amplified this concept significantly by creating a biobank of disease iPSCs. Collaborating with the Japanese pharmaceutical company Takara, Yamanaka has formed T-CiRA whose goal is to use disease iPSCs as a platform for developing new drugs to treat diseases. FOR MORE

In addition to developing new drugs, iPSCs can be used to improve the accuracy of existing drugs, which often have adverse reactions. Drugs have a sweet spot for optimal activity, yet as individuals we respond differently partly due to our varying ability to metabolize xenobiotics. Enzymes that metabolize drugs commonly reside in the liver. Using iPSCs, T-CiRA has begun to generate liver cells from patient iPSCs to profile variation in patient’s drug metabolizing ability. This new precision medicine approach will help to better stratify drug treatment groups.

Invited Comments

o Some believe that the iPS approach is not the best option for cellular therapy. Rather, the direct transformation of the stem cell to the tissue of interest may be a better way to go. This eliminates the extra step of iPS cell generation with its inherent cost implications.

o While the Japanese approach may difficult to adopt, the direct transformation approach is a personalized medicine approach that the healthcare system cannot sustain.

o The heterogeneity in other populations would make the Japanese approach more difficult.

o iPS cells will be helpful for organoid generation for the study of diseases. This could predict precise therapies for individual patients to improve efficacy and to eliminate side effects.

o Would it possible to manufacture stem cell cells for ‘off the shelf ‘ applications? Synthetic Biology may answer that question in the near future.

Stem Cell Manufacturing in Alberta

A state of the art facility opened in the fall of 2016 in the Li Ka Shing Centre for Health Research Innovation adjacent to the University of Alberta Hospital.   The new Alberta Stem Cell Manufacturing Lab, founded by Dr. Greg Corbett of ‘Edmonton Protocol’ renown, can accommodate a 6 person clinical trial and has the capacity for researchers and clinicians to develop therapies and treat patients with stem cell medical treatments in Edmonton.

The ‘Edmonton Protocol’ put Alberta’s researchers in the international spotlight when their breakthrough made possible worldwide advances in the treatment of long term diabetes patients. The ‘EP’ successfully transplants healthy pancreatic islet tissue into diabetes patients where their own pancreatic tissue would no longer respond to insulin.   Patients were once again able to self-generate insulin.

The new clinical facility is the first of its kind in western Canada enabling clinicians to grow, differentiate and package personalized and undifferentiated stem cell tissues for numerous health applications.  The Center’s first project is already underway and involves the manufacture of Hepatitis ‘C’ vaccine. FOR MORE

A Glimpse of Precision Medicine in Japan

Over the last three weeks, I had the pleasure of visiting several Japanese Universities, where I learned about their research in precision medicine. Much of my tour revolved around Japan’s effort to use human induced pluripotent stem cells (iPSCs) as a vehicle for driving precision health.

You may remember that the 2012 Nobel prize was awarded to Dr. Shinya Yamanaka of Kyoto University for his development of cellular reprogramming. Using this method, physicians are now able to generate patient-specific stem cells from patients, opening the door to customizing regenerative medicine and drug development. Since its development ten years ago, Japan has invested heavily in iPSC technology seeing this as their opportunity to lead the world. The Japanese government immediately built the Center for iPSC Research and Application (CiRA), where I was hosted by my former PhD student Knut Woltjen a native Albertan who is now an Associate Professor at Kyoto University under Yamanaka’s mentorship.

Knut Woltjen, Derrick Rancourt, Shinya Yamanaka