By Stephanie Smith

BU News Service

 

Despite the great debate over bioethical issues, stem cell research continues. Now, Boston-based researchers think they have hit upon a major development in stem cell studies, one which could benefit a large populations of patients suffering from inflammatory diseases.

A group of researchers from Brigham and Women’s Hospital, the Harvard Stem Cell Institute, MIT, and Massachusetts General Hospital have uncovered a way for adult stem cells to act as a “drug factory” at the site of inflammation in the body.

Speaking to the Harvard Stem Cell Institute, researcher Jeffrey Karp said, “If you think of a cell as a drug factory, what we’re doing is targeting cell-based, drug factories to damaged or diseased tissues, where the cells can produce drugs at high enough levels to have a therapeutic effect.”

 

Lead author Oren Levy, PhD was cautiously optimistic about the discovery’s potential to treat certain diseases associated with inflammation, such as heart attack, multiple sclerosis, and even certain types of cancer.

“It’s important to not create false hope, but we do see a lot of progress to be made,” Levy said.

Levy, started the research venture to test his hypothesis that stem cells could be used to target a localized region of the body. The study, published on Aug. 21 in the scientific journal Blood, also included study authors Jeffrey Karp, Weian Zhao, Mehmet Fatih Yanik, and Charles Lin.

Stem cells are undifferentiated cells – essentially cells that haven’t decided yet if they will become a blood cell, or a skin cell or any other kind of specialized cell. At the “stem cell” phase, these cells still have the potential to turn into any specialized cell. This study used adult stem cells, which are less controversial than embryonic stem cells only found in embryos that have not fully developed.

Researchers tweaked these adult stem cells using modified strands of mRNA, a type of single stranded genetic material similar to DNA that is naturally found in human cells. Upon mRNA insertion, the cells produced an anti-inflammatory protein, known as interleukin-10.

These modified human stem cells were injected into the bloodstream of a mouse with inflammation in the ear. The cells targeted the site of inflammation and released the interleukin-10 to reduce the swelling.

“We basically used the cells as a vehicle to deliver, and they did,” Levy said in prepared remarks.

Ultimately, the group was able to develop a type of cell that has the capability of reaching the site of inflammation and suppressing  it.

“If you think about biological therapeutic drugs, they’re a huge part of medicine, but there [are] still challenges,” he adds. “It’s hard to target them where you want them to act.”

Though this study looked at a simple local inflammation model in the ear of a mouse, the group hopes to target a clinically relevant model in the future for common conditions like inflammation in the wrists caused by arthritis. But, Levy warns, “This has a lot of potential happening in the next years to come, but it’s still early.”

This research garnered from the stem cell studies could potentially lead to treatments, or even cures, for diseases caused by chronic inflammation like atherosclerosis, arthritis, and even some cancers that progress due to inflammation.

Sarah Anderson, a student studying Economics at the University of North Carolina, Chapel Hill, was diagnosed with juvenile rheumatoid arthritis (JRA) at age three. JRA affects more than 250,000 children. Since then, she has lived with the burden that inflammatory disease has on a patient and loved ones.

“I’ve been through it all—oral medications, steroid injections, which are super painful because they have to get directly to the bone, physical therapy, and now I’m on a weekly injection,” she said. “When initially being tested, and doctors telling my mom that it could be leukemia, she said that it was the worst year of her life.”

Although the steps toward treating larger scale diseases with this type of stem cell therapy will take time and additional progress in the lab, Levy and colleagues are optimistic about the future.

“We’re harvesting the knowledge that we already have to hopefully modify cells to go to any relevant organ that needs treating,” Levy said. “We see a lot of progress for autoimmune diseases and other inflammatory diseases.”

While researchers remain optimistic, patients, like Anderson, remain somewhat skeptical. “Since joint damage is a side effect of arthritis, when not treated, I would want to see how this medication works long term,” she said. “I would love a cure one day or to stop these inconvenient injections, but when it comes to my health, I need to know with certainty that the benefits outweigh any costs.”

Now, Anderson is on a weekly regime of injections and says that after suffering for 17 years she has finally controlled her symptoms. “I have only been off medication for one year over the last 17 and that was when I was in remission in second grade,” she said. “Luckily today, even though I am not in remission, I do have it under control, but the future remains a mystery.”

Researchers say that though they are making progress with the development of the drug, there will not be an opportunity for public use for several years.

“We’ll keep on trying and keep on optimizing the process until we get a maximal response,” Levy said. “We’ll keep an open mind until we solve it.”

By Cassie Martin
BU News Service

If starfish could talk, we’d probably hear them screaming “I’m melting…melting!” Along the west coast of the U.S. and Canada, starfish are dying off in massive numbers, succumbing to sea star wasting syndrome—a mysterious illness that turns them into what scientists are calling piles of white goop.

In July, marine researchers from the University of California in Santa Cruz (UCSC) were doing fieldwork off the coast of Alaska when they noticed something strange: scores of starfish were losing their arms and developing white lesions on their bodies. The syndrome, which affects at least 10 different species, is swift. The time from infection to goop can be as short as a few days. In some regions, 95 percent of starfish populations have been wiped out.

Starfish are keystone species in many tidal ecosystems, responsible for maintaining biodiversity. A significant decrease in their populations could tip the scales, allowing other organisms such as mollusks to dominate and throw the whole system out of whack.

The culprit behind the outbreak continues to elude researchers, but suspects include viruses, bacteria, and/or environmental factors. In the past, scientists attributed starfish die-offs to warming water temperatures, which leave the multi-armed creatures vulnerable to disease-causing bacteria. But that’s not the case here. Water temperatures along the west coast are currently experiencing a cold period.

While research to identify the cause of sea star wasting syndrome continues, the good news is that starfish are resilient creatures. Although their populations are in shambles, they regenerate quickly according to UCSC experts. To learn more about current efforts to stem the disease, check out this interactive map from the UCSC Pacific Rocky Intertidal Monitoring Program.

By Angelo Verzoni
Boston University News Service

BOSTON – “Put him in a body bag!” chanted the boisterous, banner-wielding bunch of teenagers, bleeding red, white and black, at a Scarborough High School ice hockey game.

“It’s all in good fun,” Andrew Reichl, a former student at the southern Maine high school, where ice hockey is as popular as L.L. Bean backpacks, said in an email. “It’s all about extremes in high school. If you’re not saying the most outrageous things, you’re not going to get heard.”

But hard hits, especially ones to the head, are no laughing matter. Repetitive blows to the head can lead to chronic traumatic encephalopathy (CTE) in athletes and others, research suggests.

CTE is a progressive brain disease that can result after repetitive concussions, or blows to the head. The Center for the Study of Traumatic Encephalopathy (CSTE), a collaborative effort born out of the Boston University School of Medicine (BUSM) and the Sports Legacy Institute, has been researching CTE since 2008, when BUSM received a $1 million grant from the National Football League (NFL) to fund the project.

CTE is a disease that starts early on as a result of repeated blows to the head, said Dr. Robert Stern, one of the four co-directors at the CSTE, in a telephone interview. It triggers “a cascade of events in the neurons and other brain cells that lead to the accumulation of an abnormal form of the protein called tau,” said Stern. “And that abnormal form clumps together to create what are called neurofibrillary tangles. And that accumulation of neurofibrillary tangles and tau throughout the brain eventually leads to the destruction of brain cells. And as the cells get destroyed, symptoms begin.”

The symptoms are broken into three areas, explained Stern: cognitive, behavioral and emotional. Cognitive symptoms include changes in memory and changes in what are known as executive functions, such as multitasking, organization, judgment and impulse control. Behavioral symptoms include rage, problems with emotional control and changes in personality. Emotional, or “mood symptoms,” include depression, apathy and thoughts of suicide.

As the disease progresses, symptoms in all of these areas can worsen, said Stern. In some people, problems with motor functioning occur, such as loss of balance, falling or difficulty speaking. “In a subset of individuals, there’s the development of a motor neuron disease like ALS, or Lou Gehrig’s disease,” said Stern. “And then, eventually, if someone lives long enough and more brain tissue is destroyed, the person develops a full-blown dementia.”

So, is CTE an alienesque super-disease sprung up in the last decade or so?

Not quite; in fact, the longtime bane of boxers, it is far from it. CTE is the same thing that used to be referred to as “punch drunk,” or dementia pugilistica, said Stern. “We’ve known about the longterm effects of boxing, which is what ‘punch drunk’ and dementia pugilistica are, since 1928, when the first scientific article was published in the Journal of the American Medical Association.”

Exposure to repetitive brain trauma – more or less, blows to the head – is the necessary variable for developing CTE. But it is not sufficient for developing the disease. “In other words, not everyone who hits their head over and over again develops this progressive brain disease,” said Stern.

“Anyone who might have a history of being hit in the head over and over again is at risk for developing CTE, whether it’s a boxer or a football player or a hockey player or a soccer player,” said Stern. But the scope of those at risk is not limited to athletes, he clarified. There is a case of a circus clown, who had been repetitively and, it goes without saying, forcefully shot out of a cannon, who developed CTE, said Stern. “Anything that results in repetitive blows to the head can lead to CTE,” he said.

A lineman in football will hit his head 1,000 to 1,500 times a year, estimated Stern. That is around 20 to 25 g (as in g-force): “The equivalent, each one of those, of running a car into a brick wall at 35 miles per hour. Brain cells are being hurt,” he said, every play of every game and every practice.

“The symptoms of CTE do not usually begin until one’s 30s or 40s or 50s, years or decades after the person stops getting their head hit,” said Stern. And once it starts, it spreads, he said, very much like Alzheimer’s disease.

So what do athletes think?

Nicholas Neugebauer, a sophomore at Castleton State College in Vermont, continues to play football and lacrosse despite having suffered three concussions when he was in high school. “I already suffer from short-term memory loss,” Neugebauer said in a string of text messages, “and I worry about the longterm effects.” But he loves playing too much to give it up, he said.

The NFL is making an effort to increase awareness of the dangers of concussions and prevent them. But many agree that the efforts at the high-school and even college level are lackluster. “They’re making an outreach to coaches in high schools to prevent this type of damage,” William Eldred, a professor of biology at Boston University and expert in neuroscience, said in an interview.

Eldred spoke enthusiastically about the CSTE’s research. The message needs to be clearer, he said. “That’s what they’re establishing. If you have something like [a concussion], depending on the severity, either you don’t come back, or you are out for weeks and then maybe come back.”

At Scarborough High School, efforts to prevent and treat concussions are in full-swing. “The perception of concussions has changed dramatically in the past several years,” Joe Davis, the athletic trainer at Scarborough High, where football, ice hockey, soccer and lacrosse, among other sports, are popular, said in an email. “The biggest thing is to get the word out,” said Davis of the dangers of concussions, “to parents, coaches, and especially athletes.”

Less than a mile from Scarborough High, just down a grassy hill speckled with parking lots, bleachers, an expensive turf field and usually roaming students and past the elementary school and its playground, is Scarborough Middle School. “We’re in the process of creating a protocol for students post-concussion,” Patricia Bolduc, a nurse at the middle school, said in an email. “The football program is still not sanctioned by the school, so we deal directly with parents,” she said, “and have found parents to be very receptive and careful about their children’s well-being.”

As of yet, CTE can only be diagnosed postmortem. Research at the CSTE is moving toward earlier diagnosis, treatment or a cure, said Stern. But until then, awareness and prevention of concussions, especially with regard to contact sports, is key. “Our goal is to try to understand what else, in particular, leads to why one person gets the disease and another person doesn’t, including genetics and possibly specific aspects of the injuries themselves,” said Stern.

Despite efforts by the NFL and forward-thinking schools like Scarborough High and Scarborough Middle School, Stern said he is not content. “I don’t think it’s being given enough attention across all levels of sports,” he said bluntly of CTE and concussions in general.