Posted on Jun 24, 2017, 5 a.m.
Researchers set out to determine how chronic inflammation affects the brain and found a mechanism that directly links inflammation to mental illness
Approximately three-quarters of those plagued by systemic lupus erythematosus endure neuropsychiatric symptoms. Lupus is an autoimmune disease that is incurable at the moment. Medical professionals do not have a full understanding of lupus' impact on the brain. Lupus patients typically have an array of neuropsychiatric symptoms such as psychosis, seizures, nervousness, and depression. However, the extent and nature of such symptoms have not been clear until recently.
Research fellow Allison Bialas, PhD, worked with Michael Carroll, PhD at Boston's Children's Hospital to determine if changes in lupus patients' immune systems are directly responsible for the symptoms of mental illness outlined above. Their determination points to a new drug that might be able to safeguard the brain against neuropsychiatric effects of lupus as well as other diseases. Their findings were recently published in the journal Nature.
A Brief Look at Lupus
About 1.5 million Americans have lupus. It forces the immune system to combat the body's organs and tissues. As a result, the white blood cells in the body release type 1 interferon-alpha, a diminutive cytokine protein that serves as a systemic alarm of sorts to stimulate a cascade of immune activity through binding with the receptors in tissues. Yet medical researchers did not think these circulating cytokines were capable of crossing the blood-brain barrier until now. This barrier is the uber-selective membrane that determines which materials are transferred between blood and fluids in the central nervous system.
The Research Team's Work
The above-referenced researchers made use of a mouse model with lupus for their work. They found that interferon-alpha permeated the blood brain barrier to spur alterations within the brain. Once it passed across this barrier, it transmitted microglia. These are the central nervous system's immune defense cells. They were activated in an attack mode of sorts against the neuronal synapses within the brain, causing the synapses to be lost within the frontal cortex. Carroll states this mechanism connects inflammation to mental illness. The fallout of this finding will have major implications for an array of central nervous system diseases.
Blocking Inflammation's Impact on the Brain
The research team tried to minimize synapse loss by applying a drug that blocks off the interferon-alpha receptor known as anti-IFNAR. The team found anti-IFNAR provided neuro-protective effects in mice plagued by lupus. This receptor prevented synapse loss and even reduced the behavioral signs of mental illness.
What Happens Next?
CNS lupus is a brain disease that has the potential to be treated and possibly mitigated or reversed. The implications of this recent breakthrough extend beyond lupus as inflammation is central to all sorts of different conditions and diseases from chronic stress to Alzheimer’s and beyond.
Additional research will be necessary to determine the manner in which interferon-alpha crosses the blood brain barrier. However, the new findings set the foundation for subsequent clinical trials to determine the effects of anti-IFNAR drugs on CNS diseases like lupus. An anti-IFNAR drug known as anifrolumab, is currently being studied in a phase three human clinical trial to determine if it treats additional aspects of lupus.