Researchers Declare Breakthrough in Rare Brain Disease in Kids

Rare Daily Staff

Researchers from Université de Montréal and the CHU Sainte-Justine and Université de Montréal Hospital say they have determined that Rasmussen’s encephalitis, a rare and inflammatory brain disease that can lead to the destruction or removal of a part of the brain, is an autoimmune disease.

The researchers say that it has long been suspected that Rasmussen’s is an autoimmune disease, but they have been able to establish for the first time through experiments in humanized mice that it is.

“Several treatments have been proposed to slow the progression of the disease in affected children, however, these treatments have produced contradictory results, particularly in the long term,” said study co-author Alexandre Prat, a professor of neuroscience at Université de Montréal and researcher at the Centre de recherche du CHUM “In addition to shedding light on the autoimmune origins of the disease, we have proven that experimenting on humanized mice allows for a more precise diagnosis.”

Prat said in the absence of biological markers for the disease, which makes diagnosis difficult, the mice could be useful for testing various treatments and determining the best one for each individual patient.

Named for Théodore Rasmussen, a neurosurgeon who discovered it, the condition is also known as  chronic focal encephalitis. It is a degenerative disease that most often develops in children. Its causes are unknown. The disease is characterized by recurring epileptic seizures that are not responsive to antiepileptic treatments. In more serious cases, the frequency of the seizures can only be reduced by disconnecting the two hemispheres of the brain or by removing one of them. As the disease progresses, it triggers cognitive decline and severe learning disabilities. It is an ultra-rare condition, which researchers say make it difficult to find enough patients to study it and conduct clinical trials because there are so few patients.

The researchers used NSG mice, a type of humanized mice that lack an immune system. They are used to study the human immune system and illnesses, such as cancer, leukemia, HIV and sometimes certain allergies and inflammatory diseases.

“We introduced immune cells from patients with Rasmussen’s encephalitis into the mice; because these rodents don’t have an immune system, they are unable to reject the cells,” said Elie Haddad a professor in the Department of Pediatrics at UdeM. “We then observed the mice, who developed violent convulsions and brain necrosis, just like their human counterparts. Biopsies of the mice’s brains revealed immunological damage that was practically identical to that in human patients, which proves the disease’s immunological origins.”

The researchers hope to use these animals for making diagnoses as early as possible and selecting the best treatment for each sick child. If patients receive the proper treatment early, it is possible to avoid the cognitive decline brought on by the disease and forestall the need for brain surgery.

“The next step is to use NSG mice to design a standardized diagnostic protocol that can be used in pediatric hospitals,” said Prat. “These mice will become patient surrogates for making diagnoses and establishing personalized treatment protocols.”

April 10, 2018