Dear hiromichi mizuno

Take Japanese producedbcgand send it to America to treat autoimmune diseases as per the science and art of Denise l faustman

It will produce money for you

Japan BCG Laboratory

www.bcg.gr.jp/english/

Japan BCG Laboratory was established in 1952 and has produced high-quality BCG(Bacillus-Calmette Guérin) vaccine ever since. Japan BCG Laboratory is ...

In the late 1990s, former Chrysler CEO Lee Iacocca handed more than $10 million to Massachusetts General Hospital (MGH) scientist Denise Faustman and instructed her to transform an ancient tuberculosis vaccine into a cure for type 1 diabetes. Today Faustman announced the latest milestone in that project—FDA clearance to launch a large trial in people based on what her lab learned from that early research. And the 90-year-old auto magnate continues to fund her studies through the Iacocca Family Foundation, which he founded in 1984 in memory of his late wife, Mary, who died of complications from diabetes.

The trial, announced at the American Diabetes Association conference in Boston, will investigate whether treating patients with the vaccine, bacillus Calmette-Guérin (BCG), will improve natural insulin production in adult patients whose pancreases still produce small but detectable levels of the hormone. If it works, BCG might one day be used to essentially reverse the disease in some patients—even adults who have suffered from diabetes from childhood—says Faustman, director of MGH’s immunobiology laboratory and the study’s principal investigator. And it wouldn’t cost much, either, since BCG has been around for nearly a century and is available in generic form.

“We’re not only going for something cheap and safe, but also trying to figure out a good treatment that might reverse the most severe form of the disease in people who are 15 or 20 years out,” Faustman says.

Here’s how BCG works: The vaccine prompts the immune system to make tumor necrosis factor (TNF), a protein that destroys the abnormal T-cells that interfere with the pancreas’s ability to make insulin. That elevation of TNF has already been well-proven to be quite therapeutic in some settings—BCG, in fact, is approved by the FDA not only to prevent tuberculosis but also to treat bladder cancer.

Faustman’s lab spent years doing basic science experiments to show TNF can temporarily eliminate the abnormal T-cells that cause type 1 diabetes. Iacocca’s foundation, which had been supporting some of that work since coming across the lab’s earliest studies, invited Faustman to present the results of her research at a board meeting in 1999, she recalls.

Iacocca asked Faustman why she wasn’t using BCG to cure diabetes in mouse models of the disease. “I said, ‘It’s too early. We need to do more basic science,’” Faustman recalls. “He looked at me and said, ‘You know, it’s my money.’ We made a deal that if I would aggressively go forward in the mouse he would support me. He gets the credit for supporting the basic science that led to the discovery that TNF is needed in type 1 diabetes.”


Lee Iacocca’s foundation has supported basic diabetes research at Massachusetts General Hospital (Credit: AP Photo/Paul Sancya)

With continued funding from the foundation and other supporters, Faustman launched a small phase 1 clinical trial in people designed to prove that BCG would kill the bad T-cells and stimulate good T-cells in a way that would restore insulin secretion. It worked, though the positive effects were transient. So Faustman started planning a larger phase 2 study to prove that regular injections of BCG, followed by periodic booster shots, would produce a sustained response, and to determine whether that response might improve over time as the pancreas regenerates.

Still, Faustman’s team had to overcome one big hurdle before the FDA would approve the phase 2 trial: a massive shortage of BCG. Two of the biggest producers of the vaccine, Merck and Sanofi , have suffered production problems, leading to huge manufacturing delays. The issue has left some bladder cancer patients in the lurch, as reported recently in the Wall Street Journal. Faustman and her colleagues, who had been using Sanofi’s vaccine, had to go looking for an alternate supplier.

So MGH collaborated with a division of the Bill & Melinda Gates Foundation and the World Health Organization to secure the vaccine for the trial from a drug manufacturer that’s run by the Japanese government, Faustman says. “We had to get the FDA to certify that [the manufacturer's] processes are up to U.S. standards so the BCG can be used for trials,” she says. “This is not something that academics normally do, but we were determined.”

Faustman’s team has raised $19 million of the $25 million needed to complete the phase 2 study, thanks largely to the Iococca Family Foundation, which continues to be the project’s biggest source of support. “I made a promise to my late wife to find a cure for type 1 diabetes,” Iococca said in a statement. “Now my family and I look forward to the continued progress and are proud to support this effort to get closer to that goal.”

Faustman’s plan is to enroll 150 adults with diabetes, some of whom will receive BCG, with the others getting a placebo. The patients will have two injections four weeks apart and then annual injections over four years. They will continue to take insulin, though the research team will be watching closely to see if the BCG reduces the amount of insulin needed to maintain blood-sugar control, Faustman says. “We expect the metabolic effect to occur gradually over five years,” she says.

However it turns out, Faustman says, she will always be grateful to Iacocca for having the patience to continue funding the BCG research. “Many other people support us now, but the Iacocca Foundation makes a huge contribution to these trials,” she says. “He sees the big picture and is willing to look for ways to change the paradigm.”

Japan’s Government Pension Investment Fund hard to reform

Hiromichi Mizuno arrived at Japan’s $US1.1 trillion public pension fund in January with orders to shake up one of the world’s most conservative financial institutions.

The roughly 80 staff didn’t have work mobile phones. They had no access to Bloomberg terminals, considered important plumbing for financiers. A sign out the front warned people with no business at the fund to go away.
But as the new chief investment officer of Japan’s Government Pension Investment Fund, the largest publicly managed pension in the world by assets, Mizuno was getting a chance to try to fix a crucial puzzle: how to fund the retirement of the world’s oldest wealthy nation.
Retirement programs across the world, including the US’s Social Security system, are under pressure as populations age and as fewer people pay into the systems.
Japan is at the leading edge of that problem. Its solution, watched closely worldwide by investors and pension officials in other countries, is to try to boost returns by shifting more pension money into stocks after years of focusing on low-yielding government bonds.
Other countries, including China, have also loosened rules to let their pensions take on more risk in search of better returns.
Changing Japan’s pension fund has proved to be more of a minefield than Mizuno expected.
A Japanese native who worked in London at a private equity firm, Mizuno planned to recruit hot shots in stocks and foreign bonds. He told associates he wanted to experiment with new asset classes, including infrastructure and environmentally responsible companies.
Data released last week shows Mizuno has nearly finished guiding the fund smoothly through a historic shift in its basic portfolio, which sets the stage for him to reach for loftier goals. It hasn’t been an easy road thus far. He has spent much of his time managing political squabbles and courting a public that remains wary of changing a fund so integral to their financial security.
Many of the fund’s 67 million participants think investing in stocks is like throwing money away. Despite a bull market over the past two years, the Nikkei Stock Average is down 49 per cent from its peak in 1989.
Mizuno says he understands their worries, but he sees no alternative. In a recent interview with The Wall Street Journal, his first since taking the job, he says bonds will lose value over time if Japan’s economy rises out of deflation — a damaging spiral of falling wages and prices — as it may be doing.
Steering the fund is “not always a pleasant position to have”, Mizuno says. But Japan needed to try new things, he added.
Mizuno’s experience is emblematic of the broader uncertainties Japan faces as Prime Minister Shinzo Abe presses ahead with his “Abenomics” program to kickstart Japan’s struggling economy after decades of rocky growth.
So far, the program has relied mainly on monetary stimulus and government spending, which have boosted stock prices and corporate profits. But Tokyo has struggled to fully implement more meaningful long-term changes. The gains from Abenomics haven’t yet translated into sustained, steady growth or a definitive end to decades of low inflation.
Last October, at the government’s prodding, the pension fund unveiled plans to ramp up returns by increasing holdings of foreign and Japanese stocks to 50 per cent of the fund’s total, from 24 per cent previously. Only 35 per cent of the fund’s money would go into domestic bonds, from 60 per cent, while overseas bonds would rise to 15 per cent from 11 per cent. Overseas investors rejoiced. The move meant trillions of yen would begin flowing into foreign bond and stock markets. The announcement helped the Nikkei Stock Average post its biggest one-day percentage rise in over a year.
Many ordinary Japanese, however, were terrified. Some say Abe just wanted to juice the Tokyo stock market, a charge Abe administration officials denied.
Tokyo needed someone with enough market expertise to execute the pension fund’s changes without further rattling the public. A deputy cabinet secretary suggested Mizuno.
A tall, dapper man with black-rim glasses who grew up in the countryside outside of Nagoya, Mizuno studied in the US and eventually landed at Coller Capital, a London-based private equity firm where he became head of Asian investments.
He was hesitant to take the position, according to friends he spoke with, because it could harm his reputation if the fund lost money or he didn’t achieve much. As a government official, his salary would be fixed at ¥30 million ($32,000), a fraction of what ­people in his profession make in the private sector.
But Mizuno says he felt he had a duty to his country, according to the friends. He says he viewed the opportunity as an “honour” in the Journalinterview. Still, his appointment, announced without debate, added to public concerns.
Yasuhisa Shiozaki, Abe’s welfare minister who technically oversees the fund, complained to reporters and ministry officials that it would be dangerous to alter the pension fund’s portfolio without strengthening oversight. Shiozaki began drafting legislation to install a board of directors to check Mizuno’s powers.
Mizuno became frustrated, especially when comparing his job to life in London. “I used to be driving a Ferrari, and now I’m driving a tricycle,” Mizuno said soon after starting his job, according to friends he spoke with about his experience.
The Prime Minister intervened to help on February 17, according to officials familiar with the meeting. He handed Shiozaki a paper, which had four points ordering him to defer to Mizuno and abandon legislation to increase oversight, according to the paper reviewed by the Journal.
Mizuno says change is happening. The fund is nearing the end of its massive portfolio rebalancing, officials familiar with the fund’s investments have said, and data shows.
In its report, the fund said domestic bond holdings were a hair under 40 per cent of its portfolio at the end of March, from nearly 50 per cent at the end of September. The percentage of funds dedicated to foreign and domestic stocks both rose over 20 per cent for the first time on record. The fund doesn’t disclose what stocks it buys.