Wednesday, October 1, 2014

The promise of stem cell therapies is closer to reality

Edgar Irastorza was just 31 when his heart stopped beating in October 2008.

A Miami property manager, break-dancer and former high school wrestler, Irastorza had recently gained weight as his wife’s third pregnancy progressed.

“I kind of got pregnant, too,” he said.

During a workout one day, he felt short of breath and insisted that friends rush him to the hospital. Minutes later, his pulse flatlined.

He survived the heart attack, but the scar tissue that resulted cut his heart’s pumping ability by a third. He couldn’t pick up his children. He couldn’t dance. He fell asleep every night wondering if he would wake up in the morning.

Desperation motivated Irastorza to volunteer for a highly unusual medical research trial: getting stem cells injected directly into his heart.

“I just trusted my doctors and the science behind it, and said, ‘This is my only chance,’ ” he said recently.

Over the last five years, by studying stem cells in lab dishes, test animals and intrepid patients like Irastorza, researchers have brought the vague, grandiose promises of stem cell therapies closer to reality.

Stem cells broke into the public consciousness in the early 1990s, alluring for their potential to help the body beat back diseases of degeneration like Alzheimer’s, and to grow new parts to treat conditions like spinal cord injuries.

Progress has been slow. But researchers have been learning how to best use stem cells, what types to use and how to deliver them to the body — findings that are not singularly transformational, but progressive and pragmatic.

As many as 4,500 clinical trials involving stem cells are underway in the United States to treat patients with heart disease, blindness, Parkinson’s, HIV, diabetes, blood cancers and spinal cord injuries, among other conditions.

Initial studies suggest that stem cell therapy can be delivered safely, said Dr. Ellen Feigal, senior vice president of research and development at the California Institute of Regenerative Medicine, the state stem cell agency, which has awarded more than $2 billion toward stem cell research since 2006 and is enrolling patients in 10 clinical trials this year.

But enthusiasm for stem cells sometimes outstrips the science. When Gov. Rick Perry of Texas had adult stem cells injected into his spine in 2011 for a back injury, his surgeon had never tried the procedure and had no data to support the experiment.

A June review in The New England Journal of Medicine found that “platelet-rich plasma” stem cell therapies praised by a number of athletes worked no better than placebos.

Such public chatter may imply that stem cell research is further advanced than it is, said Dr. Charles Murry, a co-director of the Institute for Stem Cell and Regenerative Medicine at the University of Washington.

Slick websites advertising stem cell therapies leave the impression that such treatments are ready to use and that “the only problem is the evil physicians and government, who want to separate people from lifesaving therapies,” said Murry, a cardiovascular pathologist. “Almost every one of these places are charlatans.”

In fact, very few therapies beyond bone marrow transplants have been shown to be effective, he said.

And still to be determined is the most cost-effective way to deliver stem cells.

Scientists presumed, for instance, that a patient’s heart would repair itself better when injected with its own stem cells. But the study that Irastorza volunteered for at the University of Miami showed that patients fared just as well with someone else’s stem cells, and their bodies did not mount an immune attack against the cells.

If supported by further studies, this means that future patients won’t need immune suppressants, and that stem cells can be made in large batches — and therefore more cheaply.

Treatment for Irastorza, who received his own cells, began with the withdrawing of some of his bone marrow. Researchers took adult cells believed to be stem cells from the marrow and then inserted them through a catheter directly into Irastorza’s heart.

About a third of his left ventricle had been destroyed by his heart attack, which was attributed to a hereditary cholesterol problem. It’s impossible to know for sure whether the bone marrow cells’ descendants became heart muscle cells or if repairs were spurred some other way, but today, his doctors tell him his heart is one third of the way back to normal.

It’s enough, Irastorza said, to allow him to dance again and to be the kind of father he wants to be: “My quality of life is like night and day to before the treatment.”

Dr. Roach: How to keep ‘smoldering’ myeloma at slow pace

Dear Dr. Roach: More than a year ago, I was diagnosed with multiple myeloma in the smoldering stage, based on a bone marrow biopsy and blood tests. Every three months, my hematologist checks my blood tests and tells me that when I feel bone pain, it will be time to begin chemo. While I am in the smoldering stage, is there anything I can do to prolong the shift to the full-blown stage? I am 79 and otherwise in good health. My only symptoms are some fatigue and lack of energy.


Dear W.K.: Multiple myeloma is a type of cancer of blood cells — the plasma cells, which are responsible for making antibodies. Most, if not all, cases of myeloma have a precursor stage called MGUS, monoclonal gammopathy of uncertain significance. About 3 percent of all people older than 50 have MGUS, and about 1 percent of people with MGUS will develop MM per year. “Smoldering” MM is the diagnosis when the bone marrow biopsy shows evidence of MM but there are no other signs of MM. Signs of MM include myeloma in the bones (on X-ray or CT, called lytic lesions, since they “lyse,” or cause holes in, the bones), anemia, high calcium, poor kidney function and high viscosity of the blood, which predisposes a person to strokes.

In addition to looking for physical symptoms, your hematologist is searching for any of these findings. In addition, the amount of immunoglobulin in the blood predicts risk for developing overt MM (the higher the immunoglobulin, the higher the risk). A level over 1.5 g/dL puts you at high risk. Although trials are ongoing, there are no generally accepted treatments to prevent progression to MM for people with MGUS or smoldering myeloma.

Tuesday, September 30, 2014

Agent Orange Bill Legislation Set To Run Out October 1, 2014

Everyone knows Agent Orange is bad, and exposed veterans know that it causes certain cancers and other diseases after exposure. The Department of Veterans Affairs (VA) recognizes this, and for all of these cancers and diseases, disability compensation is practically automatic. These are called “presumptive” conditions that are presumed to be caused by the military purely because of time and date in service.

Veterans’ children have long been recognized to have birth defects and diseases resulting from their parents’ exposure to Agent Orange.  Currently, the VA recognizes many such conditions in the children of women veterans, but the list for male veterans’ children is significantly shorter. It includes only spina bifida (with the exception of spina bifida occulta).

What a lot of veterans don’t know, though, is that Agent Orange exposure has also caused numerous, serious birth defects in exposed male veterans’ children, besides spina bifida. These can include:

- Crohn’s disease
- Lupus
- thyroid disease
- chronic kidney disease
- missing parts of limbs
- webbed toes

The list is much, much larger than this. For a complete list of diseases and birth defects known to have occurred in children of vets exposed to Agent Orange, please visit the Children of Vietnam Veterans Health Alliance (COVVHA).

The Agent Orange Act of 1991 went into effect for the purpose of researching the diseases and birth defects found in exposed veterans’ children, to find out what they were, and to add them to the list of VA covered conditions.

The Act began a review of conditions in 1994 which was originally scheduled to run until 2001, but later was extended till October 1, 2014. Every few years, more conditions were added to the VA’s list. On October 1, 2014, the last review will take place, so any conditions not included in this last report will probably be left out of the VA’s list for good, unless more legislation comes into play.

It is likely we will see this last report, which covers the data from 2012, 2013, and 2014 sometime in 2015.

If you are a child of an exposed veteran, COVVHA encourages you to file a claim with the VA so that your voices can start being heard.

The instructions for doing so are found at the COVVHA website and are reproduced below:


Beauty products linked to cancer, birth defects, hormonal issues

Valerie Mason-Robinson didn’t originally plan to open Eden Organix, her natural and organic beauty products store and spa in Highland Park. The chemical engineering graduate started her career in the mainstream cosmetic industry, working in the sales departments of some of the world’s largest cosmetic companies.

Her path changed when her first child’s skin issues prompted her to learn more about some of the ingredients found in beauty and personal-care products.

“A lot of (mainstream) products contain skin irritants as well as chemicals linked to breast cancer, testicular cancer, asthma, eczema, early puberty and aging skin,” says Mason-Robinson, an aesthetician who now encourages people to use beauty and personal-care products with natural ingredients instead of synthetic ones. “To me, using those products is killing yourself softly, truthfully.”

Mason-Robinson isn’t alone in her concern about the ingredients used in many mainstream beauty and personal-care products. Several nonprofit organizations, including the Environmental Working Group and the Campaign for Safe Cosmetics, are working to eliminate chemicals they believe are linked to cancer, birth defects, hormonal issues and other health problems from cosmetics and personal care products.

“Everything from deodorant to baby shampoos contains things that you shouldn’t put on your body,” says Stacy Malkan, co-founder of the Campaign for Safe Cosmetics, which recently was involved in convincing the New Brunswick-based company Johnson & Johnson to eliminate potentially carcinogenic chemicals from some of its baby shampoos. “The skin is very effective at absorbing chemicals, and in some cases, it can be an even more direct route of exposure because it doesn’t go into your digestive system.” According to the Campaign for Safe Cosmetics, the top ingredients and contaminants to avoid in personal-care and cosmetic products include triclosan, formaldehyde, formaldehyde-releasing preservatives such as quaternium-15 and dimethyl-dimethyl, parabens like methylparaben and propylparaben, synthetic musks and hydroquinone.

The Environmental Working Group tests tens of thousands of personal-care and beauty products on a regular basis and gives each product a safety rating on its Skin Deep database online. offers a similar ratings service for all types of products. Malkan also encourages people to support the Safe Cosmetic Act, federal legislation introduced in July. If passed, this would remove chemicals linked to reproductive harm and cancer from personal-care and beauty products and set up a system for safety assessments of those products under the FDA. Corley believes as more information becomes readily available for consumers more companies will begin to remove chemicals linked to health risks from their products.

“People are buying more and more natural products,” he says. “A lot of people thought it was just a trend, but it has become a lifestyle for people. You are starting to see the green movement really move.” tests tens of thousands of personal-care and beauty products on a regular basis and gives each product a safety rating on its Skin Deep database online. offers a similar ratings service for all types of products.

Malkan also encourages people to support the Safe Cosmetic Act, federal legislation introduced in July. If passed, this would remove chemicals linked to reproductive harm and cancer from personal-care and beauty products and set up a system for safety assessments of those products under the FDA.

Corley believes as more information becomes readily available for consumers more companies will begin to remove chemicals linked to health risks from their products.


Spread of multiple myeloma halted in mice

Novel approach now being tested in a clinical trial

In an advance against cancer metastasis, scientists at the Harvard-affiliated Dana-Farber Cancer Institute have shown that a specially developed compound can impede multiple myeloma in mice from spreading to the bones.

The findings, published in the Sept. 25 online edition of Cell Reports, suggest the compound may also be able to protect human patients from one of the deadliest effects of cancer.

The research involves a new approach to metastasis, the process by which cancer tumors spread to and colonize distant parts of the body. While traditionally research has focused on the cancer cells themselves, scientists are increasingly studying the interactions between tumor cells and the tissues around them — the so-called microenvironment. In the current study, researchers explored why errant myeloma cells often settle in bones, and whether the bones could be made less hospitable to such malignant homesteading.

“While cure and survival rates have increased for many types of cancers in recent decades, most of these gains have been made in patients with primary cancers — cancers that have not spread beyond their initial site,” said the study’s senior author, Irene Ghobrial of Dana-Farber’s Center for Hematologic Oncology. “Metastasis remains one of the most formidable complications we face as cancer researchers and physicians. Improvements in the treatment of metastatic cancers have, for the most part, not been nearly as dramatic as in primary disease.”

The current study focused on multiple myeloma because it is metastatic by nature. Myeloma cells originate in the bone marrow, depart for the bloodstream, and eventually return to the bones, where they form numerous colonies — hence the name.

Ghobrial and her team knew that a substance called stromal cell-derived factor-1 (SDF-1) is a kind of protein Pied Piper, attracting certain cells to new locations within the bone marrow. They found that mice with advanced stages of myeloma had sharply higher levels of SDF-1 at the sites in the bones where metastasis had occurred.

“We reasoned that by neutralizing SDF-1, we could change the bone marrow environment to make it less receptive for multiple myeloma cells, reduce myeloma cells’ affinity for the marrow, and thereby inhibit the progression of the disease,” said Aldo Roccaro, the study’s co-first author with Dana-Farber colleague Antonio Sacco.

Working with the German biotechnology company NOXXON Pharma, the researchers tested a substance called olaptesed pegol (a PEGylated mirror-image L-oligonucleotide), which binds tightly and specifically to SDF-1. Laboratory experiments suggested that olaptesed pegol blocked the activity of SDF-1, making it a less alluring signal for tumor cells. In mice, the researchers found that olaptesed pegol altered the bone marrow, rendering it uninviting to myeloma cells. The result was slower disease progression and prolonged survival of the animals.

It isn’t completely clear what becomes of the blood-borne myeloma cells that are prevented from metastasizing to the bones, the researchers said. “We know that myeloma cells can’t survive for long if they’re circulating in the blood and can’t adhere to other tissue,” Ghobrial noted. “We saw no evidence that they had metastasized and begun to grow in other tissue, either.

“Our findings clearly document a therapeutic effect of olaptesed pegol in a mouse model of advanced myeloma,” she continued. “It is now being tested in a clinical trial of multiple myeloma patients, with more trials to come.”

Ghobrial is an associate professor of medicine at Harvard Medical School (HMS) and Roccaro is a research associate in medicine at HMS.

The research was supported by the National Cancer Institute.