FDA holds hearings on stem cell research

The way forward is paved with unknowns — and great hope

By Kathy Jean Schultz

The U.S. Food and Drug Administration will hold hearings about stem cell research this month, on Sept. 12-13. In coming months the agency will review ongoing experimental surgeries that the National Institutes of Health has been monitoring. Medical institutions and universities now investigating the complex ways that stem cells heal injury and disease are funded by private donations and individual states’ grants. No federal funding is available in the U.S. because the FDA has not approved stem cell treatments as being safe.

Although much has been demystified by science in recent decades, much is still unknown about how stem cells work. Nonetheless, they have been successfully used in a number of patient-consented, experimental surgeries, as well as in NIH clinical trials. There have also been successful surgeries outside the U.S.

There are at least two sides to every story, and there are many more than two sides to the stem cell story. The need for thorough, prudent painstaking research of the highest quality and maintained at rigorous academic standards — a long, slow process — can be at odds with patients seeking timely relief from disease, especially terminally ill patients who see that treatment works. Conventional FDA regulation faces a potentially new universe of cell biology.

One example is blindness. In cases where stem cell surgery has reversed blindness, the reason why it works is not always clear, and does not yet meet the scientific litmus test — predictive power. Only when a treatment predictably reverses blindness at a statistically significant level, repeatedly over time, does it merit legitimacy. Only when doctors know how and why it’s working is it considered a cure.

To determine if stem cells do cure, the FDA might consider classifying them as “drugs,” which means they would need to undergo years of costly approval processes before they could be sold or deemed to have “proven” benefits.

During years-long approval processes, the “drug” classification could mean that experimental surgeries and clinical trials could be curtailed — or even stopped. This does not sit well with patients whose health and even lives have been restored by experimental surgeries.

Vision was restored for Doug Oliver, 54, of Nashville, Tenn., during a clinical trial surgery, after he was nearly blind for 11 years. His treatment and subsequent vision recovery in 2015 could be classified as “unproven” by the FDA, although he states that he is living proof. “I went from legally blind to legal-to-drive in eight weeks,” says Oliver, describing his recovery. When his vision loss began, due to a rare hereditary condition, doctors described it as “incurable.” Stem cells extracted from Oliver’s own bone marrow were used in the surgery that healed his eyes.

Should a patient’s own body parts be considered a “drug” that needs federal approval for the patient’s own use? Questions arise about whether stem cells should even be classified as “drugs” that need any kind of FDA approval, timely or not. Bone marrow stem cells extracted from one’s own bones and then used to heal another body part could be categorized just like storing one’s own blood in a blood bank for future emergencies.

Sorting out FDA concerns

The stems of plants spawned the name “stem” cells. Although it is tiny, a plant stem holds within it the potential to sprout vegetables, vines, thorns, leaves, fruit or tree trunks. In the same way, a tiny human stem cell holds within it the possibility of generating many different types of larger cells.

Cells in the eyeball are not like cells in the heel, cells in the heel are unlike cells in the spine, and fingernail cells are not like liver cells. The fact that stem cells can differentiate — become different — is key. A cell inside a kidney adapts into doing some kind of kidney function over a lifetime, while a cell located in the knee aligns with other knee cells. Every cell has its place and its job. A thigh muscle does not make a heart pump, nor does an ear cell heal the ankle.

Just like a seed that becomes a giant tree, one way to understand stem cells is that they have the potential to grow into becoming any body part. When surgically implanted into a particular body part, they can adapt. A stem cell can become a toe cell, or blood platelets. Experimental surgeries have restored the vision of blind patients by inserting stem cells in the eye exactly where they can replace dead cells, and become working eyeballs.

The vast numbers of human cells are one reason it’s hard to pin down exactly how stem cells work. The brain alone has some 5,000 different types of cells. “You can’t just plop in a stem cell and hope that it’ll figure out what to be, how to network and with whom…”, says Johns Hopkins Medicine researcher Dr. Valina Dawson. “In the lab, we’re trying to figure out what are the cues and instructions you have to give these cells to nudge them along to become the kind of cells or tissues you want in the end … it isn’t entirely understood what determines a cell’s fate.”

Stem cell therapies come with risks. One is cancer. Transplanted stem cells proliferate quickly. This speed is their great advantage in healing. However, multiplying rapidly is also what cancer does. Sometimes the surgical process leaves the stem cells cancerous. The reason is not yet understood.

Regeneration is not news

Cells that can change into something else have been known to science for a long time. A spider sits on a tree branch, and an hour later, there is a web there too. One thing — a spider — becomes two things — a spider and a web. The spider’s cells produce a second visible item.

The mechanism of spider webs is an area of cell regeneration that science is coming to understand. Silk that spiders produce for webs is astonishingly strong. Some spider silk is tougher than the Kevlar in bullet-proof vests. A violin built from webs of the Golden Orb spider recently debuted in London, resulting in this sci-fi-scented headline: “A visionary scientist has made a violin with spider silk — and it sounds extraordinary.”

A suddenly visible, super-strong substance, webs come from proteins inside spider glands. The spider converts these proteins into a fiber, and can then spin out feet or even yards of fibers woven into webs. So where there was no web before, new cells are produced that form webs.

Newts, a type of lizard, and planaria, a type of water worm, can both regrow themselves. If a newt loses a leg or a foot, the missing limb can regrow. A planaria worm can be cut into pieces and each piece regrows into a new worm. Although human skin can heal after wounds, and human blood can replenish following bleeding, people cannot regrow a finger or a leg. Cell regeneration appears in many forms, but not that one.

Unpacking all the labels

As science harnesses more information, it comes freighted with a confusing number of labels. Four often-investigated types are: embryonic stem cells, cord cells, adult stem cells and pluripotent stem cells.

Embryonic stem cells are derived from human embryos, and they can grow and adapt to replace any kind of cell in the body. This is why they are found in embryos: they repeatedly regenerate so a baby becomes a child and then an adult.

These extremely adaptable stem cells typically are obtained from unused embryos donated by couples using a medical process called “In Vitro Fertilization” (IVF) to become pregnant. The IVF process is sought out by people who have tried and failed to become pregnant, and it pairs a man’s sperm and a woman’s egg together in a laboratory dish. The process generates many more embryos than a couple needs to achieve a pregnancy. If the couple wants to have just one child, many other eggs that were fertilized during the process are unused embryos. The use of embryonic stem cells is steeped in ethical debate.

Umbilical Cord stem cells are found in the umbilical cord, during a baby’s birth. These cord cells can proliferate quickly and have the capacity to differentiate into various types of cells. Compared to embryonic stem cells, cord cells have less power to change into all cell types.

Parents of newborns can save and preserve cord stem cells in cord banks offered by many companies now, so they can store the umbilical cord of their child immediately after birth. Families preserve these cells so that they are available for the child’s future medical treatments.

Adult stem cells are taken from adult patients’ own bodies. They are often extracted from a person’s skin, or bone marrow. Adult stem cells have been used successfully in the treatment of lung disease, some cancers, orthopedic injury, some blood and immune disorders, blindness and other diseases. Bone marrow has proven well-suited because, normally, stem cells in bone marrow function as a repair shop — it is their regular job to regenerate blood cells all the time.

Adult stem cells are not as adaptable as embryonic stem cells. They don’t differentiate as well. This limits where and how they can be used.

One risk factor is that adult stem cells have lived longer than cord cells or embryonic cells; they might have abnormalities to due to environmental hazards or toxins. Lifelong disease-fighting or poor nutrition can wear one down, and adult stem cells have not necessarily aged gracefully, leaving them with less healing potential than cord cells or embryonic cells.

“Pluripotent” stem cells are created from adult stem cells. Scientists are discovering how to manipulate adult stems cells, in a laboratory, in a process that turns them into cells almost as powerful as embryonic stem cells. This process sometimes involves moving genes around inside the adult stem cells to make them more like embryonic cells. These are then called “pluripotent” stem cells.

Back to the future: The road to pluripotency

The mystery of how to change adult stem cells into pluripotent stem cells is the focus of much investigation around the world, as well as of the 2012 Nobel Prize in Medicine.

Traditionally, biological growth was thought to be irreversible: once a tree, never a seed again; once an adult, never a baby. If an embryonic cell becomes a nose, it could never revert back to being an embryonic cell. It was a one-way street, going forward but never back.

Science is discovering methods of reprogramming adult cells so they revert back to being an embryonic cell. When adult cells are reprogrammed back into being embryonic, they are called “pluripotent” because they now have many (plural) potentials. Like an embryonic cell, they can become anything.

Adult stem cells contain genes: The reprogramming sometimes re-arranges the cells’ own genes. This turns the stem cell’s clock back. This process usually adds nothing foreign or new into a patient’s biochemistry, it just re-arranges things.

The exact method of achieving reprogramming as yet eludes science, but what is known so far about the process is that it’s delicate, complex and requires perfect coordination and timing. Cancerous mutations can occur if moving genes around is not done with precision.

These newly minted lab procedures and constantly evolving discoveries may come under FDA review. Although the process of turning back a cell’s clock uses only the patients’ own cells, that manipulation could be considered a “drug” requiring approval before use. The argument that a patient’s own cells should not be classified as a drug, but rather the same way a patient’s stored blood is, becomes complicated. Reprogramming genes can be different than simply storing blood in a bank.

A 2016 FDA analysis concludes: “Cells manufactured in large quantities outside their natural environment in the human body can become ineffective or dangerous and produce significant adverse effects, such as tumors, severe immune reactions, or growth of unwanted tissue.” The creation of pluripotent adult stem cells definitely takes place “outside their natural environment in the human body,” because it’s in a lab.

Kevin McCormack is Senior Director of Public Communications and Patient Advocate Outreach at the California Institute for Regenerative Medicine. “Right now if you take someone’s stem cells, say from fat from their belly, and then put them in another part of their body, say their knee to treat arthritis, and do that all in the same procedure without in any way altering those cells then that’s considered OK by the FDA,” McCormack wrote in an email.

“If however, you take out that same fat, put it through a centrifuge or use some other method to concentrate the stem cells, then introduce it later that day or another day into the same patient, that is considered — in the language of the FDA — doing more than ‘minimal manipulation’ to those cells and that then categorizes them as a drug. And drugs need to be approved by the FDA — through the clinical trial process — before they can be made available to the wider public.”

If stem cell treatments do become classified as drugs, giant pharmaceutical companies will likely be involved in testing their effectiveness. Billions of stem cell patients worldwide translates into potentially mountainous profit. And the pharmaceutical industry could possibly put the cost of the eventually-approved process out of reach for many patients. With regard to profits, ethics and methodology, the industry does not have a problem-free history. If the FDA classifies adult stem cell manipulation in a way that pharmaceutical companies would be the only ones permitted to sell it, ethical challenges erupt.

Stem cell clinics misrepresenting their offerings as safe have popped up in recent years, and left patients in worse shape, not better. A number of unscrupulous clinics offering questionable stem cell treatments have caused patients injury because of misleading advertising. On behalf of taxpayers and the use of taxpayer money allocated to future research, the FDA could clamp down on them for misrepresenting stem cell miracles, likening fraudulent clinics to snake oil peddlers of the past.

However, it’s not only get-rich-quick clinics that have exaggerated the benefits of medical innovation. “Every major pharmaceutical company in the last 15 years has settled federal charges of fraudulent marketing. So, consumers should be skeptical about any advertising claims connected to stem cell treatments,” Kathleen Sharp, author of 2011’s Blood Medicine, said in an email. Blood Medicine is one of many books documenting the trail of illness and even death brought on by drugs the pharmaceutical industry knew to be unsafe.

The FDA may decide that clinical trials can continue. Doug Oliver, whose blindness was diagnosed as “incurable” until clinical trial surgery restored his vision, says, “I want these treatment trials to be available sooner and to more people who have no hope of treatment in the near future for blindness.”

Stopping stem cells’ trial surgeries would, in his view, “‘Sentence’ so many currently blind or near-blind people to an unnecessary, sightless future, when I am proof there is much still to be clinically discovered and treatments still to be clinically developed with patient self-determination and their informed consent.”

http://www.centerforhealthjournalism.org/2016/09/05/fda-holds-hearings-stem-cell-research

September 5, 2016

© 2016 Kathy Jean Schultz

www.kathyjeanschultz.com

Twitter: @kjschul