Getting Stem Cell Products to Market? It’s Fate

Stem cell and regenerative medicine companies have proliferated in the short space of a few years. Even during the recent economic downturn, their stocks surged anywhere from 10-40%.

Now two firms –- Fate Therapeutics in La Jolla, Calif., and Novartis in Basel, Switzerland –- are in a race to develop stem-cell drugs that may save the lives of thousands of blood cancer patients who need a transplant of bone marrow or umbilical-cord blood and can’t find an adequate match. And Fate, currently a privately-held startup, may be winning.

Both firms’ drugs aim to harness the body’s ability to heal itself. Fate’s first clinical trial focuses on a molecule known as FT1050. The molecule appears to stimulate proliferation of hematopoietic stem cells –- which give rise to blood and immune cells –- and helps guide them to the bone marrow. If successful, the drug would be used initially in bone-marrow transplants and umbilical-cord blood transfusions to treat cancer and blood diseases.

Treatment for leukemia or lymphoma currently kills off most of a patient’s hematopoietic stem cells, and the best way to repopulate them is through bone marrow transplanted from a matched donor. When a bone-marrow donor match is unavailable, oncologists turn to umbilical-cord blood, which is rich in stem cells and requires only a partial tissue-type match.

"The mission of Fate Therapeutics is to develop small molecules and biologics that modulate adult stem cells within the body for regenerative medicine," says Fate’s president and CEO, Paul Grayson. "As our first SCM clinical candidate, FT1050 represents the initial step in our approach –- using a small molecule to treat cells ex vivo but creating an in vivo regenerative effect. With FT1050, we are trying to affect stem cell biology in the body, improving the reconstitution of a patient’s blood and immune system."

Scientists at the Harvard Stem Cell Institute are working with Fate on a clinical trial for FT1050 that started two months ago. Switzerland’s Novartis may not get into the clinic until next year with its stem cell therapy. Novartis is working with researchers at the University of Minnesota.

There are three possible sources of blood stem cells for patients who need transplants: bone marrow, peripheral blood and umbilical-cord blood.

According to Dennis Confer, medical director of the National Marrow Donor Program, bone marrow and peripheral blood are plentiful in volume but “must come from either a relative of the patient or someone whose blood is a close match to the patient’s. While umbilical-cord blood doesn’t need to be as close a match, the amount of cord blood from a single birth is often inadequate to treat an adult or an older child,” he says.

High tech regenerative medicine shares some commonality with alternative medicine — treatments such as chiropractic, homeopathy, naturopathy, acupuncture and herbology, in that both share the same goal of helping the human body to heal itself. Alternative medical practices combine a variety of "building up" and support techniques for the body’s natural immune system. Regenerative medicine seeks to restore the structure and function of damaged tissues and organs. It is also has the potential to repair organs that have become permanently damaged. It includes:

1. Medical devices and artificial organs –- creating new body parts from a patient’s own cells and tissues.
2. Tissue engineering and biomaterials — using biomaterials to create a mold and engineering cells to grow, for example, in the form of a heart valve.
3. Cellular therapies — using stem cells as one way of stimulating the body to repair itself.
4. Clinical translation — putting promising therapies into active trials.

This short video describes recent advancements in the use of cord blood stem cells and regenerative medicine as a possible treatment for over 70 diseases:

MIT Technology Review reports that Fate Therapeutics has focused much of its research on induced pluripotent stem (iPS) cells, adult cells that have been reprogrammed back to an embryonic state and have the same flexible developmental potential as embryonic stem cells. Rather than trying to use these iPS cells to treat disease, they are using them to learn more about which pathways are important for activating or inhibiting stem-cell development.

The Fate Therapeutics’ drug, discovered and now being tested by Harvard researchers, is a prostaglandin, a type of fat. Leonard Zon, a Harvard University professor who works at Children’s Hospital in Boston, identified it through research with zebrafish embryos. Their transparent quality let researchers view cells that have been engineered with proteins so that they glow in different colors.

Fate Therapeutics’ early-stage clinical trial involves giving FT1050 to 12 patients who’ve undergone chemotherapy for lymphoma. The patients will each receive two units of umbilical-cord blood: one that’s been treated with the stem-cell-modulating drug, and another that’s been left alone. The trial is primarily a safety study, but because the two units were harvested from two different newborns, researchers can use the genetic differences to track the cells and determine if FT1050-treated stem cells can more efficiently take hold and prosper in bone marrow.

Because FT1050 is believed to affect fundamental pathways present in all hematopoietic stem cells, FT1050 may end up improving the efficiency and success of treatment with hematopoietic stem cells from any source, including from bone marrow and peripheral blood.

Combining a drug like FT1050 with the body’s own stem cells may also prove to be a successful therapy for a number of other diseases –- and ultimately fulfill the promise of regenerative medicine not only to save lives in the near term, but ultimately to build a bridge to longevity and anti-aging biotechnologies.