A new study by Israeli researchers could be a step towards diagnosing Parkinson’s disease years earlier than is currently possible, potentially opening the door to successfully fighting the disease’s progression.
A team at the Hebrew University of Jerusalem isolated a key factor that is a common, but rarely discussed, symptom of degenerative disease: constipation.
Although chronic constipation is a common problem as people age and is often not a sign that something in particular is wrong, it has also been directly related to Parkinson’s, sometimes appearing in patients up to 20 years before being diagnosed with disease.
Start Start-Up Israel’s Daily Start-Up by email and never miss our top news Subscribe for free
Currently, doctors lack a validated laboratory methodology for the definitive diagnosis of Parkinson’s disease, which is mainly diagnosed based on motor symptoms that indicate that the patient suffers from the disease, including tremors, stiffness and difficulty walking, balance and coordination .
By the time these symptoms are clearly visible, the brain has lost too many dopamine cells to recover. Currently available treatments target the symptoms of the disease, rather than reverse its progression.
Professor Joshua Goldberg, Department of Medical Neurobiology, Hebrew University (Courtesy of Joshua Goldberg)
But early diagnosis can be critical. Many promising treatments failed at the test stage, but according to Professor Joshua Goldberg of the Hebrew University, who led the recent study, this may not be because something was inherently wrong with the treatment – but simply because the diagnosis was made too late for a potential cure to be useful.
The Hebrew University research – published on Wednesday in the journal Science Advances and led by Professor Goldberg of the Department of Medical Neurobiology in collaboration with Professor Jochen Roeper of Goethe University in Frankfurt, Germany, pointed to constipation as a potential early marker.
Parkinson’s disease has long been associated with the formation of tiny deposits of protein residues within brain cells called Lewy bodies, in honor of Dr. Friedrich Lewy who discovered them in 1912. It is not clear whether these protein deposits are the cause of the degenerative disease or symptom of it. In fact, according to Goldberg, it could be a little bit of both.
But the presence of Lewy bodies cannot be easily detected in living patients, and their prevalence in the brain has only been observed posthumously in people who have suffered from the disease. Alone, they are not very useful as a diagnostic tool.
An illustrative image of a patient with Parkinson’s disease (Obencem; iStock by Getty Images)
One of the first places where Lewy bodies are found in the brain is an area that affects gastrointestinal activity – specifically the upper gastrointestinal tract.
The team of Prof. Goldberg sought to identify the specific underlying mechanism that connects the presence of Lewy bodies in the brain with constipation. Constipation not caused by Parkinson’s – the type that is not governed by brain problems – usually focuses on the large intestine, not the upper gastrointestinal tract. Therefore, scientists hope that the identification of the mechanism responsible for constipation in the upper gastrointestinal tract will allow them to signal the cases that are of concern.
In their study, the research team found a way to detect how Lewy bodies impact the upper gastrointestinal system, using a specific protein, alpha-synuclein, which is known to be the main constituent of Lewy bodies.
The team overexpressed alpha-synuclein in mouse brain cells that modulate activity in the upper gastrointestinal tract.
“The result was that overexpression of the protein caused these brain cells to shrink and their electrical activity to decrease,” concluded the study. The rats then developed constipation of the type that is associated with Parkinson’s disease.
A model to slow down the digestive system after the expression of the alpha-synuclein protein in the brain stem, as part of a study focusing on the early diagnosis of Parkinson’s disease among those suffering from constipation. (J. Goldberg / J. Roeper)
“So this is likely to be the process that also occurs in humans in the early stages of Parkinson’s disease,” according to the study.
“As far as we know, this is the first time anyone has described a causal chain of events connecting between how the alpha-synuclein protein impacts brain cells and the first symptoms we know of before this disease,” said Goldberg, publicizing the potential of discovery.
“Consider a 55- to 60-year-old patient who suffers from constipation. We may one day develop a test based on the neural changes we have discovered to determine whether there is a neural factor at play that could suggest Parkinson’s disease, ”he said.
Goldberg emphasized that an early diagnosis would probably not be based solely on constipation and that a battery of tests would be used to indicate the early presence of the disease.
This could allow potential curative treatments to be administered before massive cell death develops in the brain, leaving the patient permanently and increasingly disabled.
Although he admitted that it was still hypothetical, he said: “One day in the future we are confident that we will be able to identify a variety of biomarkers – including physiological ones, like the one we propose – that will allow us to definitively diagnose the disease much earlier than we are currently able to. . “
