A study conducted on mice by researchers at Inserm and UPMC (Pierre and Marie Curie University) offers a new type of immunotherapy approach for treating Alzheimer’s disease. This involves amplifying a specific population of T lymphocytes that regulate immune and neuroinflammatory mechanisms that develop during the disease.
These results are published in the journal Brain.
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A new immunotherapy strategy for treating Alzheimer’s disease. This may be validated by the new work carried out by the Inserm team “Immune System, Neuroinflammation and Neurodegenerative Diseases” at UMRS 938 “Saint-Antoine Research Centre” (Inserm/UPMC) in Paris. In recent years, a body of substantive work has enabled the start of gaining further insight into complex immune and neuroinflammatory mechanisms associated with Alzheimer’s disease. The Inserm team at the Saint-Antoine Research Centre offers further proof of concept on the efficacy of innovative immunotherapy strategy in mice that is based on an immunomodulation approach.
Researchers have shown, in earlier work with mice, that a specific population of T lymphocytes, known as T regulators (or Treg), modulated specific Ab peptide T lymphocytes that accumulate in the brains of sick people. “Treg cells may act in different ways to modulate T lymphocyte response in general. However, there are other aspects of neuroinflammatory reactions observed in this type of disease”, states Guillaume Dorothée, Inserm Research Fellow in charge of this study. As such, researchers chose to evaluate the effect of Treg cells on disease progression using a mouse model.
Interleukin-2: Therapeutic Strategy
To do this, they either depleted or amplified Treg cells at the early stage of the disease. They found that a Treg deficiency accelerated the onset of cognitive disorders and was associated with a decrease in the presence of microglial cells in deposits of Ab peptide.
“Additional studies seem to suggest a change in the functional profile of these inflammatory cells that are chronically activated during the disease which would have a rather beneficial role early in the disease process”, according to the researcher.
By contrast, prolonged Treg amplification using low doses of interleukin-2 injected intraperitoneally increases the microglial cell response and delays the onset of memory impairment.
This immunomodulation approach involving the injection of low doses of interleukin-2, already tested in some bone marrow transplant clinical protocols and for type 1 diabetes, now seems to be a new therapeutic strategy for Alzheimer’s disease. Researchers are already planning a pilot clinical trial in humans and are also considering the possibility of modulating some specific sub-populations of T lymphocytes to refine the response.
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Regulatory T cells delay disease progression in Alzheimer-like Pathology
Cira Dansokho1,2*, Dylla Ait Ahmed1,2*, Saba Aid2,3*, Cécile Toly-Ndour1,2*, Thomas
Chaigneau1,2, Vanessa Calle1,2, Nicolas Cagnard4, Martin Holzenberger2,3, Eliane Piaggio5,6,
Pierre Aucouturier1,2, Guillaume Dorothée1,2.1 INSERM, UMRS 938, CdR Saint-Antoine, Laboratory "Immune System, Neuroinflammation
and Neurodegenerative Diseases", Hôpital St-Antoine, F-75012, Paris, France.
2 Sorbonne Universités, UPMC Univ Paris 06, UMRS 938, CdR Saint-Antoine, Hôpital Saint-
Antoine, F-75012, Paris, France.
3 INSERM, UMRS 938, CdR Saint-Antoine, Laboratory "Neuroendocrine mechanisms of
longevity and age-related diseases", Hôpital St-Antoine, F-75012, Paris, France.
4 Bioinformatics Platform, Faculty of Medicine Paris Descartes, Hôpital Necker-Enfants
Malades, F-75015 Paris, France.
5 INSERM, U932, Institut Curie, Section Recherche; Center of Clinical Investigation (CICBT-
507), F-75005, Paris, France.
6 Sorbonne Universités, UPMC Univ Paris 06, CNRS, UMR7211, Immunology-
Immunopathology-Immunotherapy, F-75013 Paris, FranceBrain, 1er février 2016
DOI: dx.doi.org/10.1093/brain/awv408