Parkinson’s disease is one of the most frequent disorders affecting movement and the nervous system. Currently, approximately 4.1 million people suffer from Parkinson’s disease throughout the globe, in Spain alone more than 300,000 people are affected. Typical symptoms of the disease are slowness of movement, rigidity, frequent shaking and an increasingly stooped posture. The cause is the continuous death of nerve cells in the brain, which produce the messenger substance dopamine. Scientists are working to gain insights into the mechanisms which lead to the loss of nerve cells that produce dopamine.  

Recent and cumulative data point to the involvement of brain cells, called astrocytes as key players in neuroinflammatory responses in Parkinson’s disease. Researchers in stem cells and neurodegeneration from the Bellvitge Biomedical Research Institute (IDIBELL) and the Institute of Biomedicine of the University of Barcelona (IBUB), Dr. Consiglio and Dr. Raya, in collaboration with neurologists form the Movement Disorders Unit at the Hospital Clinic (Dr. Tolosa and Dr. Garrido) showed that in Parkinson’s disease, astrocytes are reactive and attack and kill nerve cells which produce dopamine in the midbrain. The findings were published online in Journal of Clinical Investigation Insight. 

The team based its research on the use of human skin cells derived from affected patients and healthy subjects. These skin cells were converted into stem cells (iPSC), and differentiated into midbrain nerve cells specific to the unaffected individual and astrocytes specific to the patients. They found that astrocytes derived from the iPSC of patients with Parkinson, secreted high levels of an inflammation-promoting molecule called interleukin-6 (IL-6), which killed a large number of the nerve cells, but this did not appear to be the case with healthy astrocytes. “While mild inflammation can be beneficial for many neural processes, the overproduction of IL-6 may worsen the symptoms of PD and may be an important therapeutic target,” said co-first and senior study author Dr. Meritxell Pons, from IDIBELL and the University of Barcelona. 

Importantly, adding to the neuronal cultures the IL-6 antibody which blocks the effect of IL-6 secreting astrocytes, Tocilizumab (an antibody which is already being used daily in the hospital to treat Rheumatoid arthritis), largely prevent the death of the nerve cells, said Dr. Manel Juan, an immunologist of SJD Barcelona Children’s Hospital and Hospital Clínic and co-author of the study. 

Moreover, when they examined the state of astrocytes in postmortem brains of Parkinson’s disease patients, they found an unusually high number of astrocytes expressing IL6 in the midbrain of Parkinson’s patients, even at early stage of the disease. These cells are commonly found in the brains of patients suffering from diseases in which the immune system attacks the brain. 

Although culture system did not include many cell types involved in potentially relevant immune responses, our findings highlight the potential role of astrocyte-mediated inflammatory signaling in PD, opening new avenues for clinical intervention,” says Prof. A. Consiglio, head of the Stem Cell and Neurodegeneration group at the IDIBELL and professor at the Faculty of Medicine and Health Sciences of the University of Barcelona. Her group is about to launch a study on inflammation in early PD. “If we could find the right way to modulate the immune system we may be able to slow the disease process”, Consiglio added. 

Reference of the article: 

Meritxell Pons-Espinal, Lucas Blasco-Agell, Irene Fernandez-Carasa, Pol Andrés-Benito, Angelique di Domenico, Yvonne Richaud-Patin, Valentina Baruffi, Laura Marruecos, Lluís Espinosa, Alicia Garrido, Eduardo Tolosa, Michael J Edel, Manel Juan Otero, José Luis Mosquera, Isidre Ferrer, Angel Raya, Antonella Consiglio. Blocking IL-6 signaling prevents astrocyte-induced neurodegeneration in an iPSC-based model of Parkinson’s disease. 

JCI Insight 2024 Feb 8;9(3):e163359. 

doi: 10.1172/jci.insight.163359. 

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).