Eye-opener: Japanese doctor's work with iPS cells puts macular degeneration on notice

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Eye-opener: Japanese doctor's work with iPS cells puts macular degeneration on notice

Science has Dr. Masayo Takahashi’s mother to thank, in a way, for some of the most notable developments in regenerative medicine using stem cells.

More than 35 years ago when Takahashi was contemplating which career she would pursue once she graduated from high school in Osaka, it was her mother who stepped in to offer firm guidance.

“I didn’t want to be a doctor at all, but my mother told me I should join the medical department,” Takahashi, 57, says with a laugh.

The old adage that mothers know best rings true in this instance: Takahashi studied medicine at Kyoto University and went on to specialize in ophthalmology, a branch of medicine that treats eye disorders.

For her pioneering work in treating eye disorders and diseases Takahashi was the inaugural recipient of the $150,000 Ogawa-Yamanaka Stem Cell Prize in 2015 from the Gladstone Institutes for her “trailblazing research.” The previous year, Nature, a British science journal, included Takahashi in its annual list of the 10 people who mattered in science.

For the past 25 years Takahashi’s research has focused on using stem cells to treat eye diseases and disorders.

In 2014, a team led by Takahashi and her colleagues at the Riken Institute’s center for biological development in Kobe made global headlines when, in a world-first, they successfully transplanted cells from induced pluripotent stem cells, or iPS cells, onto a patient’s eye.

Dr. Paul Knoepfler, a biomedical scientist and stem cell expert who heads the Knoepfler Lab at U.C. Davis School of Medicine in California, described Takahashi’s work as offering a blueprint for others in the regenerative medicine field.

“The use of IPS cells to make retinal cells provides real hope for macular degeneration, a disease for which otherwise there isn’t much that doctors can do for patients,” Knoepfler wrote in an email.

Takahashi’s research centers on how stem cells can be used to treat retinal diseases such as age-related macular degeneration, which causes cloudy and blurry vision and affects everything, including our ability to read, drive and recognize faces.

It was at the Salk Institute in San Diego, where Takahashi was a postdoctoral researcher, in the mid-1990s that she became captivated by the medical possibilities of stem cells, which would form the basis of her clinical research work.

Since 2014, Takahashi’s team has carried out six clinical surgeries using stem cells derived from iPS cells. Takahashi said that in all six operations “the survival of the cells” succeeded.

Her entire career, Takahashi has gone back and forth between clinical work and research. She attends to patients once a week at the state-of-the-art Kobe Eye Center, located near the Riken campus in the city.

“It’s very important to do both,” Takahashi said in a recent interview, referring to her work as a scientist and a medical doctor. “Nowadays it’s more difficult because the clinical demands are getting higher and higher.”

Through her outpatient work, Takahashi was well aware of the enthusiasm and interest in her team’s pioneering clinical operations.

Around 600,000 people in Japan suffer from age-related macular degeneration, which can cause blurred vision and in more serious cases lead to blindness. A 2014 study by The Lancet revealed that, by 2020, the number of people with the disease is projected to be 196 million, increasing to 288 million in 2040.

“I know the suffering patients are going through,” Takahashi said. “I’ve seen thousands of patients, I know (their needs) very well and their” desire to get better.

Because of the substantial cost of the surgery, estimated to be around ¥10 million, allied to the lengthy process the trials take, it’s still a way off before surgery using iPS cells becomes more common.

Takahashi said a third round of clinical studies will begin after her team submits applications to the relevant medical bodies sometime next year.

In some respects Japan is an outlier when it comes to clinical applications of stem cell research. Many countries have been slower to allow them, but the central government has thrown its weight behind the study and application of stem cells. Much of that support is derived from the fact that iPS cells were first developed by Nobel Prize winner Shinya Yamanaka at Kyoto University in 2006.

“The government loves iPS cells,” Takahashi said.

Takahashi recalled that when her laboratory at Riken, which has about 50 scientists and researchers, submitted its first protocol in 2012, it generated controversy and push back in the scientific community.

She puts that down to an information deficit.

“The ophthalmology community doesn’t know (enough) about the iPS cells, and they think this is risky. And the basic research community doesn’t know the clinical situation — for example what kind of risk we can tolerate. So many people were against moving ahead.”

One way around this, Takahashi believes, would be for greater collaboration among doctors, scientists, researchers and the pharmaceutical industry.

As an example, Takahashi highlighted the Japanese Society for Regenerative Medicine.

“It’s a very strong society and many doctors (there) are developing cell therapy.” Part of the organization’s role is to help explain advances to health officials and politicians so as to better inform legislation and policy.

Although Takahashi would characterize herself as a reluctant leader, she’s been instrumental in establishing the Kobe Eye Center, where she sees patients once a week.

Even before Takahashi came to Riken 10 years ago, she had long been thinking about the concept of a next-generation eye hospital.

The result is the cutting-edge Kobe Eye Center, which opened in December 2017. Although still fledgling, Takahashi hopes that by bringing together different but related elements all under one roof — clinics, laboratories and space for startups in the medical community — the institute will foster greater collaboration.

For the design of the hospital, Takahashi had one of the most innovative companies in the world in mind: Apple.

“I said to Dr. Miyake (a Riken colleague) ‘please make it like an Apple Store so that it doesn’t look like a hospital.’ I wanted it to be a place (where) patients wanted to come.”

 

The centerpiece is the “Vision Park,” a white-walled open space reception area, designed by architect Kentaro Yamazaki. It features a climbing wall and a library as well as a display area where visitors can try out some of the technology used to aid people with impaired vision.

In many ways Takahashi is also an outlier in Japan, where less than 15 percent of science researchers are women. While she has never experienced any prejudice — in fact she says she has received great support throughout her career — Takahashi says that the gender imbalance could be corrected if, during the formative years of education, more was done to encourage girls to be ambitious with their careers.

When that happens, then perhaps the pantheon of famous Japanese scientists and researchers who have received Nobel Prizes will also start to resemble the society they are from. And perhaps here, too, Takahashi will lead the way.

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Publication Date
Wed, 04/24/2019 - 00:00