Therapy Areas: Central Nervous System
Neuromyelitis Optica Linked to Antibody Exposure During Fetal Development, Feinstein Institutes Study Finds
22 April 2022 - - Research from scientists at US-based The Feinstein Institutes for Medical Research shed new clues into why offspring of mothers with meuromyelitis optica spectrum disorders NMOSD might be affected and published their findings in Science Translational Medicine, the institute said.

Neuromyelitis optica spectrum disorders (NMOSD) are inflammatory diseases of the central nervous system leading to eye pain, blindness and even paralysis. NMOSD mostly affects women of childbearing age and may cause abnormal pregnancies.

NMOSD is identified by the presence of a disease-specific autoantibody that binds to aquaporin-4 the main water channel in the brain which provides fast water transportation across cell membranes.

While most studies focus on the role of AQP4 antibodies in NMOSD, its long-term effect on the developing brain of children born to mothers with this autoimmune disease remains largely unknown, until now.

The new study found that in utero exposure to maternal AQP4 antibodies could affect the development of the blood brain barrier and alter specific brain cells in male offspring, but not females, in an animal model.

Building on decades of research, the recent preclinical paper led by the Feinstein Institutes' Lior Brimberg, PhD, and Munich's LMU Klinikum's Simone Mader, PhD, suggests that when a fetus is exposed to AQP4-antibodies, it can impede development.

That can result in a leaky BBB, which is meant to protect the brain, as well as neuronal and cognitive impairment.

Recognizing the presence of this particular antibody may lead to an earlier diagnosis and treatment interventions to improve pregnancy outcomes.

It is well documented that in utero exposure to maternal autoantibodies that bind fetal brain protein can alter development and lead to neurodevelopment disorders, including autism spectrum disorders.

This new study shows that during embryonic development, exposure to AQP4 antibodies leads to the interrupted formation of the brain's vascular system and functional and cognitive complications.

The next step is to perform a follow-up of children who were born to mothers with NMOSD to assess the spectrum of effects of maternal AQP4 antibody.

Researchers also need to investigate why males are more vulnerable to the impact of the AQP4 antibodies, the effects of antibody concentration levels, maternal medication or indirect consequences of maternal illness and genetics.

Drs. Brimberg and Mader credit the success of the study through their collaboration with Patricio Huerta, PhD, Bruce Volpe, PhD, David Eidelberg, MD, An Vo, PhD, Dr. Diamond and others.

The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State.

Encompassing 50 research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its five institutes of behavioral science, bioelectronic medicine, cancer, health system science, and molecular medicine.
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