The basic biological mechanisms that underpin autoimmune disorders are finally coming to light. Researchers in Boston’s Longwood medical area — a neighborhood where the streets are flanked by hospitals, research institutions and academic centers — are setting the stage for a new wave of future therapies that can prevent, reduce or even reverse symptoms of disease.
Inside the lab of Michael Carroll, PhD, scientists are working to understand how and why immune cells start to attack the body’s own tissues; it turns out the immune system’s B cells compete with each other in true Darwinian fashion. On the way to this discovery, the lab has flushed out new potential drug targets that could ease autoimmune symptoms — or stop them entirely — by “resetting” the body’s tolerance to itself.
The implications for a link between inflammation and synapse loss go beyond lupus because inflammation underpins so many diseases and conditions, ranging from Alzheimer’s to viral infection and even to to chronic stress. In which case, are we all losing synapses to some varying degree? Carroll plans to find out.
“We’ve found that chronic inflammation and autoinflammatory disorders can originate from genetic mutations to MDA5 that cause it to misrecognize ‘self’ as ‘non-self,’ essentially launching the immune system into self-attack mode,” said Hur. …
The human body’s innate immune system employs a variety of “sensors” for identifying foreign invaders such as viruses. One such viral sensor is a receptor called MDA5, found in every cell of the body.
Inside each cell, MDA5 constantly scans genetic material, checking if it’s native to the body or not. As soon as MDA5 identifies the genetic signature of a viral invader, it trips a system-wide alarm, triggering a cascade of immune activity to neutralize the threat.
But if a genetic mutation to MDA5 causes it to confuse some of the body’s own genetic material for being foreign, “false alarms” can lead to unchecked inflammation and disease. Scientists from Boston Children’s Hospital have discovered a new link between MDA5’s ability to discriminate between “self” and “non-self” genetic material — called RNA duplexes — and a spectrum of autoimmune disorders. …
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’s 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.…
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.
Chronic, 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. …
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.
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. …
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.