September 22, 2020

What if the Parkinson started



It is a kind of birth signal with delayed effect. A study published yesterday in “Nature Medicine” shows that people who are affected by Parkinson’s disease at an early age (before age 50) may have developed the disease-causing cells from the same day they were born. Somehow, they came into the world with cell groups that, after passing unnoticed decades, become pathogens in adulthood. The finding, announced by doctors at Cedars-Sinai Medical Center in Los Angeles, also suggests that a molecule could serve as therapy to prevent the development of pathology in these cases.

Cases grow in young people

It has long been known that Parkinson’s disease is triggered when the cells responsible for the production of dopamine (the substance that controls, among other things, muscle movement) deteriorate and die. Patients begin to feel symptoms of this deterioration: slowing of movements, muscle stiffness, tremor, loss of balance.

Unfortunately, the exact mechanism of disease production is not as well known. The implications of the dopamine production failure are known, but not the causes of cell failure. The majority of those affected begin to observe the symptoms after 50 or 60 years. But a growing percentage of cases (around 10 percent) emerge between 20 and 50. This group has been given attention to this study. But carrying out their research, Cedars-Sinai scientists used a family of stem cells known as iPSCs (Induced Pluripotent Stem Cells) obtained from patients with early parkinsons. The job is to extract cells from adult tissue (skin or fat, for example) and roll back their evolution to an embryonic state. That is, a reversal is caused in the development of the cell until it becomes the undifferentiated cell that it was before specializing. Carried to that state, rejuvenated cells can become any other cell. It is as if we send an engineer back to school to begin his education as a lawyer.

The authors of this study have converted these iPSCs into dopamine producing neurons genetically identical to those of each patient. By culturing them in the laboratory, experts have been able to recreate how those cells developed since the patient was just an embryo. That is, they have simulated the development of neurons under normal conditions to compare it with the pathological mode in which they developed in the patients studied. The researchers detected two abnormalities that can cause the deterioration of dopaminergic cells: the accumulation of a protein called alpha-synuclein and certain defects of lysosomes (cellular organelles responsible for managing the digestion residues of the cell)

The most surprising thing is that some of these errors accumulate for more than 30 years before the disease emerges. That is, in the cases of patients who develop the disease prematurely, the failures may begin to develop shortly after birth.

Experts have tested in the laboratory some molecules that can be used to reverse accumulated cell errors. One of them, called PEP005, has been very effective in reducing algae-synuclein levels. There is a circumstance that this substance (PEP005) is approved by the health authorities for the treatment of precancerous pathologies of the skin. That is, it is a medicine whose safety has already been proven for other pathologies. In the event that its effectiveness was confirmed to stop this Parkinson’s trigger, the time needed to make it available to patients would be shortened.

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