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Discovery Funded by Lupus Research Alliance Grant Could Help Prevent Psych Symptoms in Lupus

July 13, 2017

Discovery Funded by Lupus Research Alliance Grant Could Help Prevent Psych Symptoms in Lupus

Dr. Michael Carroll

Up to 75% of patients with systemic lupus experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and in rare cases psychosis. With grant funding from the Lupus Research Alliance, a team of world-class scientists discovered one reason why – a breakthrough finding that also points to a new drug currently in clinical trials, anifrolumab, as a potential treatment to prevent these effects of lupus on the brain.

Dr. Michael Carroll, Harvard professor of pediatrics at Boston Children’s Hospital first found that the earliest neuro-psychiatric symptoms among people with lupus are accompanied by a protein released by the white blood cells, cytokine interferon-alpha (IFNa), that acts as an alarm system to mistakenly activate the immune system. But before his landmark study co-authored with colleague Dr. Allison Bialas, no one thought this cytokine was getting into the brain at high enough levels in lupus to affect brain function.

Dr. Allison Bialas

Including Harvard Medical School professor and lupus luminary Dr. George Tsokos, Carroll’s team discovered that interferon-alpha does seem to pass through the blood-brain barrier to cause the immune defense cells of the central nervous system to destroy synapses – the minute space where electric nerve impulses are transmitted between two nerve cells. The synapses affected are in the frontal cortex, the area of the brain responsible for problem solving, memory, language, planning, judgement, impulse control, and social behavior.

“We’ve found a mechanism that directly links inflammation to mental illness,” said Dr. Carroll. “This discovery has huge implications for a range of central nervous system diseases.

Dr. Carroll’s team went on to discover that an investigational class of drugs that blocks the activity of interferon-alpha could reduce the loss of these important synapses in mice with lupus. These mice showed less symptoms of mental illness such as anxiety and trouble thinking.

Study authors concluded: “While CNS lupus remains a heterogeneous disease with many symptoms and probably many causes, our findings suggest that some CNS lupus patients may benefit from anti-IFNAR treatment. Therefore, our findings suggest a novel mechanism for CNS lupus and provide a rationale for expanding future clinical trials to include CNS lupus patients…”

Lupus Research Alliance Co-CEO and Co-President Kenneth M. Farber commented, “The discovery by Dr. Carroll’s team is incredibly exciting with implications for people with other autoimmune-related diseases as well as people with CNS lupus. This work exemplifies the scientific continuum made possible by our grant program – identifying novel therapeutic targets for potential treatments and informing the clinical trial process with translational research.”

One anti-interferon-alpha drug, anifrolumab, is currently being tested in Phase III clinical trials as a potential treatment for people with lupus without active central nervous system involvement. Anifrolumab is a new monoclonal antibody in development by Mediummune, the biologics research and development arm of the biopharmaceutical company AstraZeneca.

Click here to read the press release issued by Harvard Medical School.


Discovery Funded by Lupus Research Alliance Grant Could Help Prevent Psych Symptoms in Lupus

July 13, 2017

Discovery Funded by Lupus Research Alliance Grant Could Help Prevent Psych Symptoms in Lupus

Dr. Michael Carroll

Up to 75% of patients with systemic lupus experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and in rare cases psychosis. With grant funding from the Lupus Research Alliance, a team of world-class scientists discovered one reason why – a breakthrough finding that also points to a new drug currently in clinical trials, anifrolumab, as a potential treatment to prevent these effects of lupus on the brain.

Dr. Michael Carroll, Harvard professor of pediatrics at Boston Children’s Hospital first found that the earliest neuro-psychiatric symptoms among people with lupus are accompanied by a protein released by the white blood cells, cytokine interferon-alpha (IFNa), that acts as an alarm system to mistakenly activate the immune system. But before his landmark study co-authored with colleague Dr. Allison Bialas, no one thought this cytokine was getting into the brain at high enough levels in lupus to affect brain function.

Dr. Allison Bialas

Including Harvard Medical School professor and lupus luminary Dr. George Tsokos, Carroll’s team discovered that interferon-alpha does seem to pass through the blood-brain barrier to cause the immune defense cells of the central nervous system to destroy synapses – the minute space where electric nerve impulses are transmitted between two nerve cells. The synapses affected are in the frontal cortex, the area of the brain responsible for problem solving, memory, language, planning, judgement, impulse control, and social behavior.

“We’ve found a mechanism that directly links inflammation to mental illness,” said Dr. Carroll. “This discovery has huge implications for a range of central nervous system diseases.

Dr. Carroll’s team went on to discover that an investigational class of drugs that blocks the activity of interferon-alpha could reduce the loss of these important synapses in mice with lupus. These mice showed less symptoms of mental illness such as anxiety and trouble thinking.

Study authors concluded: “While CNS lupus remains a heterogeneous disease with many symptoms and probably many causes, our findings suggest that some CNS lupus patients may benefit from anti-IFNAR treatment. Therefore, our findings suggest a novel mechanism for CNS lupus and provide a rationale for expanding future clinical trials to include CNS lupus patients…”

Lupus Research Alliance Co-CEO and Co-President Kenneth M. Farber commented, “The discovery by Dr. Carroll’s team is incredibly exciting with implications for people with other autoimmune-related diseases as well as people with CNS lupus. This work exemplifies the scientific continuum made possible by our grant program – identifying novel therapeutic targets for potential treatments and informing the clinical trial process with translational research.”

One anti-interferon-alpha drug, anifrolumab, is currently being tested in Phase III clinical trials as a potential treatment for people with lupus without active central nervous system involvement. Anifrolumab is a new monoclonal antibody in development by Mediummune, the biologics research and development arm of the biopharmaceutical company AstraZeneca.

Click here to read the press release issued by Harvard Medical School.



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