Stories about: inflammation

A surprising new link between inflammation and mental illness — and a potential drug to protect the brain

A synapse being attacked by microglia, which causes neuropsychiatric symptoms in lupus
In the brain, a synapse (red – see diagonal “spine” across center of photo) is seen being wrapped around and attacked by immune cells called microglia (green), leading to synapse loss. Credit: Carroll lab / Boston Children’s Hospital

Up to 75 percent of patients with systemic lupus erythematosus — an incurable autoimmune disease commonly known as “lupus” —  experience neuropsychiatric symptoms.  But so far, our understanding of the mechanisms underlying lupus’ effects on the brain has remained murky.

“In general, lupus patients commonly have a broad range of neuropsychiatric symptoms, including anxiety, depression, headaches, seizures, even psychosis,” says Allison Bialas, PhD, a research fellow working in the lab of Michael Carroll, PhD, of Boston Children’s Hospital. “But their cause has not been clear — for a long time it wasn’t even appreciated that these were symptoms of the disease.”

Collectively, lupus’ neuropsychatric symptoms are known as central nervous system (CNS) lupus. Their cause has been unclear until now.

Perhaps, Bialas thought, changes in the immune systems of lupus patients were directly causing these symptoms from a pathological standpoint. Working with Carroll and other members of his lab, Bialas started out with a simple question, and soon, made a surprising finding – one that points to a potential new drug for protecting the brain from the neuropsychiatric effects of lupus and other diseases. The team has published its findings in Nature.

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A filtration technology poised to cure sepsis

Sepsis is the most common cause of death in infants and children worldwide, and its incidence is increasing. Damage is caused not only by the bloodstream infection itself but by the systemic inflammatory cascade it triggers — which has been difficult to control without also causing long-lasting immune suppression. During a five-minute Ignite Talk at the 2015 Boston Children’s Hospital Global Pediatric Innovation Summit + Awards, Brian McAlvin, MD, a critical care intensivist at Boston Children’s Hospital, introduced the audience to a filtration technology that could cure systemic inflammatory response syndrome (SIRS).

SIRS, McAlvin noted, is the underlying mechanism for a variety of diseases, not just sepsis. His invention, the Antibody Modified Conduit, is essentially a small tube with antibodies painted on the inner surface that recognize and remove the inflammatory agents. “This technology allows us to choose the inflammatory molecules in the circulation,” says McAlvin, “and take them out of the blood as the condition evolves by changing the antibody that’s present.”

The talk won the pitch competition, earning McAlvin an Apple watch, a one-on-one mentoring session with an influential venture capitalist and a meet-and-greet with Boston Children’s innovation acceleration team, VCs and other stakeholders.

See more posts and videos from the Global Pediatric Innovation Summit.

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Looking within cells to control inflammation

blood_vessel_shutterstock_142125664Chronic, unresolved inflammation can be quite harmful, right down to the cellular level. At the macro level, it has links to cancer, diabetes, heart disease and other degenerative conditions.

This is why the body keeps a tight rein on the inflammatory response and maintains a host of factors that resolve inflammation once the need for it (for instance, to clear an infection or heal an injury) has passed.

We know pretty well which factors work between cells to turn on and turn off inflammation. That knowledge has led to the development of drugs like ibuprofen, acetaminophen and naproxen, all of which temper pro-inflammatory factors.

However, when you look at the signals and signaling pathways within cells, things get more complex, especially when it comes to factors that turn off inflammation. We haven’t completely grasped the full complement of proteins that transmit these internal anti-inflammatory signals. If we did, we could potentially add new drugs to our pharmacopeia to regulate or resolve inflammation or maintain cells in a non-inflamed state, and perhaps help prevent rejection of transplanted organs and tissues.

David Briscoe, MD, and his team at Boston Children’s Hospital’s Transplant Research Program, has taken the field one step closer to grasping those internal pathways by studying a cellular protein called DEPTOR.

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Cancer, inflammation, platelets and aspirin: Learning new tricks from an old drug

There are a couple of ways by which aspirin might affect cancer. (cpradi/Flickr)

Aspirin does a remarkable number of things in the body, enough that it’s said it would never win approval today from the Food and Drug Administration as an over-the-counter drug.

But among those functions are some that may explain something that doctors have recognized for some time: patients with cancer who have been taking aspirin tend to have better outcomes.

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It’s not the stem cells but what’s inside them that matters for babies with lung disease

The molecular equivalent of a message in a bottle could open up the possibility of stem cell-based therapies for newborn lung disease — but without the cells. (aturkus/Flickr)

Three years ago, Stella Kourembanas, MD, and S. Alex Mitsialis, PhD, thought they had a major breakthrough in treating pulmonary hypertension (PH) — dangerously high blood pressure in the pulmonary artery (the vessel that carries blood from the heart to the lungs) — and bronchopulmonary dysplasia (BPD) — a chronic lung disease that can affect babies born prematurely or who were put on a ventilator.

The two diseases are complex and serious, often occur together and are currently incurable.

The solution for PH and BPD, the two researchers from Boston Children’s Division of Newborn Medicine thought, was to protect the babies’ fragile lungs with a kind of stem cell called mesenchymal stem cells (MCSs), which can develop into lung tissue.

Their preclinical studies were pretty conclusive. If they transplanted MSCs in mouse models of BPD and PH, the mice didn’t develop the lung inflammation that triggers the disease.

But the results were a little confusing.

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Stopping the pain of sickle cell disease at its source

sickle cell pain
The pain of sickle cell disease can be unbearable. But there’s a new view emerging on how that pain comes about, one that has spurred a new clinical trial aimed at stopping the pain at its source. (stevendepolo/Flickr)

If there’s one thing most patients with sickle cell disease will agree on, it’s that sickle cell hurts. A lot.

The characteristic rigid, sticky, C-shaped red blood cells of this inherited disease tend to get stuck in the small blood vessels of the body. If so many get stuck in a vessel that they cut off blood flow, the body sends out a warning signal in the form of searing pain that doctors call a pain or vaso-occlusive crisis (at least, that’s the historic view; more on that in a minute). The pain can happen anywhere in the body, but most often occurs in the bones of the arms, legs, chest and spine.

Preventing flare-ups—and stopping them when they happen—is a major part of the care plan for any patient with sickle cell. Right now doctors try to avoid pain crises largely by diluting a patient’s blood with fluids or transfusions, thereby keeping the numbers of sickled cells relatively low.

What these treatments don’t do is tackle the pain directly. Doctors can use pain medications, but over time, patients can become tolerant to painkillers, requiring ever-larger doses. What’s needed is something that can stop the complex cascade of events that ignite a pain crisis.

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Radiation sickness: A two-drug combination could block radiation’s double hit

A two-drug combination could help raise the odds of surviving toxic doses of radiation released through accidents like those at Chernobyl (above) or Fukushima, or by a nuclear or radiological weapon. (Kamil Porembinski/Flickr)

Radiation can have its benefits – look at radiation therapy for cancer, or imaging technologies like X-rays and CT scans that use radiation to peer within our bodies. But high doses, from malfunctioning medical equipment, accidents like those at Chernobyl or Fukushima, or nuclear or radiological weapons, can be toxic or even lethal.

Right now, there are treatments in development that could raise the odds of surviving exposure to toxic doses of radiation, but only if given within a few minutes or hours of exposure. Ofer Levy of Children’s Division of Infectious Diseases and his collaborator Eva Guinan at Dana-Farber Cancer Institute have hit upon a new-two drug combination that markedly increased survival in mice when given as late as 24 hours after exposure.

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