A door to new treatments: Parkinson’s origin would be in the intestine

A door to new treatments: Parkinson's origin would be in the intestine

Dr. Rodrigo Pacheco, an academic at the Faculty of Medicine and Science, leads a line of research focused on understanding the origin of this devastating disease, in order to find ways to stop its development.

the disease of Parkinson’s It is a neurodegenerative disorder that affects about nine million people worldwide, and whose prevalence has doubled in the last 25 years. In the midst of an alarming epidemiological scenario, aggravated by the aging of the population, the Dr. Rodrigo Pachecoresearcher of the Faculty of Medicine and Science of the U. San Sebastián and the Scientific and Technological Center of Excellence Ciencia & Vida, seeks to clarify the origin of this disease, and thereby find new possibilities to treat it.

The onset of Parkinson’s symptoms is generally slow but progressive. The classic symptoms usually appear when the neuronal degeneration is already very advanced, including tremors in the hand, slowness in the movement of the extremities or muscular rigidity. Speech may become monotonous or slurred, the face may lose expression, or the arms may not swing naturally when walking. In addition, there is a wide range of non-motor symptoms; some appear early, such as sleep disorders or intestinal inflammation, and others later such as psychosis, cognitive impairment and mood disorders. The progressive loss of physical and mental capacity leads to total disability.

Rodrigo Pacheco explains that “in Parkinson’s disease, an abnormal protein is generated in the brain called alpha synuclein. The immune system recognizes this protein as a threat, and triggers an inflammatory response against it. So this autoimmune response destroys a type of neurons in the brain that are those that control voluntary movements.

However, the research led by Dr. Pacheco has come to the hypothesis that this autoimmune response that occurs in the brain begins in the gut, through mechanisms that it currently seeks to elucidate. Inter alia, this hypothesis is supported by the early onset of intestinal inflammation in Parkinson’s patientswhich occurs several years before the onset of motor symptoms.

Together with his team, they have discovered that the intestinal flora plays a fundamental role in triggering the disease in genetically susceptible individuals, along with T lymphocytes, which are immune system cells involved in the autoimmune response. “We believe that the intestine is where the response of T lymphocytes against alpha synuclein is generated, the same response that in the future attacks neurons in the brain and generates motor problems,” he points out.

The scientist claims that in Parkinson’s disease there is an alteration of the intestinal microbiotacausing among other things the production of short chain fatty acids in an inappropriate proportion. It is important to note that these acids are metabolites produced exclusively by bacteria, but they can act on the cells of our body. Thus, today it seeks to explain how this change in the composition of short-chain fatty acids that occurs in Parkinson’s affects the behavior of the immune system, and to determine the relationship between short-chain fatty acids and the development of the disease.

For this, Dr. Pacheco has received the support of the Michael J. Fox Foundation, Founded by the actor who starred with Christopher Lloyd in the science fiction trilogy “Back to the Future,” it is dedicated to finding a cure for disease by funding scientific and therapeutic advances around the world.

Parallel, carries out an edge of applied research that seeks to develop an immunotherapy capable of turning off specifically the autoimmune response, and the destruction of neurons associated with Parkinson’s. In 2022, a FONDEF project was awarded that currently seeks to evaluate the efficacy and safety of this therapy in Parkinson’s models in preclinical models.

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Written by Editor TLN

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