INSERM: The involvement of the immune system in neurological diseases suggests that immunotherapy, which has shown its effectiveness in the area of cancer and autoimmune diseases, is also of major interest in the treatment of neurodegenerative diseases. This has been shown by the teams of Nathalie Cartier-Lacave (Inserm Research Director, Inserm/CEA Joint Research Unit 1169, “Gene Therapy, Genetics and Epigenetics in Neurology, Endocrinology, Cardiology and Child Development”) and David Klatzmann (Director of Inserm/Pierre and Marie Curie University Joint Research Unit 959, “Immunology – Immunopathology – Immunotherapy,” and head of the biotherapy department at Pitié-Salpêtrière Hospital, AP-HP), whose work is published today in the journal Brain. The researchers have proven that a molecule called interleukin-2 (IL-2), from the immune system, is able to control inflammation in the brain cells, which is implicated in neurodegenerative diseases such as Alzheimer’s disease, and can restore impaired cognitive functions in the animal model.
There are many interactions between the central nervous system and
the immune system. The cells of the immune system circulate in the brain
and can play a role – direct or indirect – in neurological diseases.
Thus a direct role has been demonstrated in multiple sclerosis, and a
direct role mediated by inflammation has also been found.
Neurodegeneration leads to neuroinflammation, which helps to amplify the
initial neurodegeneration, generating a vicious circle that aggravates
the disease. In Alzheimer’s disease, amyloid peptide β (Aβ) aggregates
in the extracellular senile plaques, around which reactive astrocytes
and activated microglial cells accumulate. These cells help to dissolve
these plaques, and secrete cytokines that regulate the intensity of the
brain’s immune response.
Moreover, recent work has shown that mice deficient in IL-2 have
diminished faculties for learning and memory, reminiscent of Alzheimer’s
disease (AD). Furthermore, IL-2 is currently being evaluated for the
treatment for several autoimmune diseases in terms of its ability to
stimulate regulatory T lymphocytes (Tregs), the role of which is to
The authors first demonstrated a strong decrease in IL-2 levels in
biopsies from patients who had died of Alzheimer’s disease. This led to
them to evaluate the therapeutic potential of this molecule in a mouse
model of Alzheimer’s disease. The mice were treated at a stage where
they already had brain involvement. This long-term treatment caused an
expansion and activation of regulatory T lymphocytes in the brain, and
led to a reduction in amyloid plaques.
The researchers showed that this reduction in amyloid “load” was
accompanied by substantial tissue remodelling marked by an improvement
in synaptic structure and function. This improvement is synonymous with
recovery of memory deficits.
While untreated mice failed memory tests, treated mice had results
comparable with normal mice. These beneficial effects on amyloid plaques
and synaptic plasticity are accompanied, in the vicinity of the
plaques, by the activation of astrocytes, a type of cell identified as
having a protective role in Alzheimer’s disease.
“This work demonstrates the interest of immunotherapies for the
treatment of Alzheimer’s disease, and especially the interest of
interleukin-2,” the authors believe. “This treatment attacks the
consequences of the disease, the synaptic loss and cognitive symptoms
that accompany it. Its therapeutic potential now needs to be assessed in
humans,” they conclude.