Cell Study Provides Hope for Treatment of Parkinson’s Disease
By Alice Melão
Deregulation of calcium levels in nerve cells has been linked to early symptoms of Parkinson’s disease. Now, researchers at Aarhus University have found that inhibition of a protein called SERCA can prevent calcium variations and protect nerve cells from degeneration.
This finding may open new therapeutic avenues to treat Parkinson’s motor symptoms, but also non-motor symptoms such as sleep disorders, gastrointestinal problems, anxiety, and depression.
The study, “Alpha‐synuclein aggregates activate calcium pump SERCA leading to calcium dysregulation,” was published in the journal EMBO Reports.
The team showed that in nerve cells with the same type of stress involved in Parkinson’s disease, there is a significant loss of calcium, a basic element in the body without which cells cannot function and eventually die.
The reason behind this observation seems to be the fact that in these cells, α-synuclein aggregates — protein aggregates thought to be behind Parkinson’s development — interact and activate a calcium pump known as the SERCA protein. Interestingly, this process is specific to α-synuclein clumps, as isolated molecules did not interact or activate SERCA.
To further confirm the relevance of these findings, the team analyzed samples of human brain collected from patients affected by dementia with Lewy bodies, characterized by α-synuclein aggregates. They again found the same pattern in which α-synuclein clumps interacted with SERCA and promoted calcium transport outside of the cell.
“The study indicates that the treatment of calcium disturbances is meaningful because the nerve cells are protected. This may help to prevent the disease from developing into such a disabling disease as would otherwise be the case,” Cristine Betzer, PhD, investigator at the brain research centre DANDRITE at Aarhus University and lead author of the study, said in a press release.
By inhibiting SERCA activity with a chemical compound that specifically blocks SERCA in a worm model of Parkinson’s, calcium levels became more stable and cell survival improved. Importantly, inhibition of SERCA protected nerve cells from α-synuclein aggregates’ neurotoxic stress.
“Experiments in the United States with similar models have shown that once the worms with the Parkinson’s protein have lived for eight days, their nerve cells begin to die. In our study, we treated the worms with an inhibitor against the calcium pump and then counted the nerve cells in the worms. And there were many cells left. Which is a sensational and encouraging result,” Betzer said.
Although these findings cannot be directly translated to the human disease they can open new study opportunities that may be useful for the development of new, more efficient therapies.
“Our study points towards the usefulness of treating patients throughout the whole course of the disease, as the calcium pump will otherwise continue to pump and thus contribute to the patient’s symptoms,” Betzer added. “Perhaps the protection of nerve cells can also mean that the damage caused by Parkinson’s disease in the brain does not develop as severely as it otherwise would.”
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Source:: Parkinson’s Today
Pre-clinical research may slow effects of Parkinson’s
by: ABC 33/40
ABC 33/40′ spoke with two people who live with the disease about new findings from Purdue University researchers.
Published in the scientific journal Molecular and Cellular Neuroscience, the researchers say they have pinpointed an important compound in the development of Parkinson’s disease in the brain.
Their work could be significant because it may impact how we treat the disease in several ways: like better therapies, new drugs and earlier diagnoses or preventative care.
Two men gave reporter Patrick Thomas a glimpse into what new treatments in their lives could do.
Whether he stands or sits, with shaky hands and trembling feet, Parkinson’s is life for Wayne Cook for the last ten years. “The things that you, used to take for granted,” Cook says as he tries to raise his left hand to his chest but can’t hold it still. “The fine motor skills are difficult.”
The same goes for Ken Cater over the last nearly 13 years of his life. “But you know it’s tough. Right now I’m dealing with a progressive disease,” says Cater.
Which Purdue University researchers say when they located the compound called Acrolein, it may lead to discoveries that alleviate symptoms of Parkinson’s. Cook tries to explain how it affects his speech. “You get something here (points to his brain) and then you know what you want to say, but it just stops right here. It won’t come out all the way.”
Cater explains what he thinks most fighting the disease want right now. Cater says, “The Holy Grail that we are looking for right now is something that can slow or stop the progression of the disease.”
Right now the research includes work that has been tested in animal models and cells, not humans.
Cook says he is even willing to be a part of any research that may eventually include human testing. “I’m anxious for it to happen. If they have got a study and they need volunteers I raise my hand,” says Cook.
But through the research, scientists say they lessened and reversed effects of Parkinson’s using the drug Hydralazine
Since it’s still only pre-clinical research Cater says he will wait and see. “I’m hopeful for a cure in the near future if not at least better treatments,” he says.
If you have questions about living with Parkinson’s as a patient or caretaker, the Parkinson Association of Alabama may be able to help.
Source: Pre-clinical research may slow or reverse effects of Parkinson’s, patients weigh in
Tears May Be Used as Biological Marker to Detect Parkinson’s Disease
Tears may be used to diagnose Parkinson’s disease, according to preliminary findings of a study that will be presented at the 2018 American Academy of Neurology’s (AAN) Annual Meeting in Los Angeles, California, April 21-27.
“We believe our research is the first to show that tears may be a reliable, inexpensive and noninvasive biological marker of Parkinson’s,” Mark Lew, MD, the study’s author from the Keck School of Medicine of University of Southern California, said in a press release.
Parkinson’s disease is mainly characterized by selective loss of neurons that produce dopamine in a brain area called substantia nigra. Patients with Parkinson’s typically exhibit Lewy bodies – protein clumps mainly composed of aggregated alpha-synuclein – in the brain, leading to nerve damage and disease progression.
Besides pathological changes in the brain, the disease also affects nerve function in the periphery. As the secretory cells of the tear gland are stimulated by nerves, researchers hypothesized that nerve changes in Parkinson’s could result in altered protein levels in tears.
The scientists collected tear samples from 55 Parkinson’s patients and 27 healthy controls who were the same age and gender.
The tears were analyzed for the levels of four proteins. The results revealed that levels of normal, non-clumped alpha-synuclein were lower in Parkinson’s patients than in controls. However, levels of unhealthy, aggregated alpha-synuclein were increased in tears of Parkinson’s patients (1.45 nanograms per milligram of tear proteins versus 0.27 nanograms, respectively).
Researchers hypothesize that the secretory cells in the tear gland could themselves produce these different forms of alpha-synuclein, which would be secreted directly into tears.
“Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson’s disease and those who don’t in a noninvasive manner is exciting,” Lew said.
“And because the Parkinson’s disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier,” he added.
Nonetheless, larger studies need to be done to evaluate whether these changes in alpha-synuclein levels can be detected in tears from Parkinson’s patients before symptoms start.
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Source:: Parkinson’s Today
Naked Art to celebrate Valentine’s, raise money for local causes
PAA is thrilled to be the beneficiary of a Parkinson’s Patients Art Show, hosted by Naked Art Gallery. Below is a great article from Iron City Ink that details the personal connection between Parkinson’s Disease and Vero Vanblaere, owner of the Naked Art Gallery.
Parkinson’s Foundation Enrolls 10,000th Patient in Largest Clinical Trial of the Disease Ever
The Parkinson’s Foundation has enrolled the 10,000th patient in the largest clinical trial of the disease yet to be conducted.
Among the critical discoveries so far, the research has shown that regular visits to neurologists, more exercise, and more attention to mental health could help improve patients’ wellbeing.
The Parkinson’s Outcomes Project is evaluating a broad range of factors associated with the disease, including medications, treatments, movement symptoms, cognition, anxiety and depression, and the disorder’s burden on caregivers.
Launched in 2009, the project has become a comprehensive platform for studying the lives of Parkinson’s patients. And it has led to the formation of a consortium of 29 experts in five countries.
The study includes over 100 people who have lived with Parkinson’s for more than 30 years and 83 who learned about their diagnosis before they were 30 years old. Its records include 25,000 visits to doctors and information from almost 9,000 caregivers.
Key conclusions drawn from the study include:
Regular visits to neurologists should be a priority for patients and caregivers because it could save thousands of lives a year.
Recent research has listed regular visits to a neurologist as an important step in Parkinson’s management. However, in a 2011 study, only 58 percent of 138,000 Parkinson’s-related difficulties led to neurologist care. Race was a significant demographic predictor of neurologist treatment, with non-whites being less likely to receive care.
Doctors should give patients’ physical activity more attention because studies have shown that increasing exercise and movement to at least 2 1/2 hours a week can slow the decline in patients’ quality of life.
Researchers have found that, in Parkinson’s, it’s not the type of exercise a patient engages in, but the frequency of the workout that’s important. Physical therapists recommend exercises whose goals include improving balance and coordination, flexibility, endurance, and strength.
Patient’s mental health should be a priority because researchers have found that depression and anxiety are leading factors in patients’ overall health.
Depression is one of the most common non-movement symptoms of the disease, with up to 60 percent of patients affected at one time or another.
Finally, doctors should do a better job of addressing gender differences between patients. A key reason is that many men can rely on wives and other family members for daily support and doctor visits. Women are less likely to have family caregiver support and be more frequent users of formal, paid caregiver services.
This discovery is supported by recent findings that confirm these gender disparities, such as a study in Neurology in 2017.
“We have obtained a wealth of information in what now represents the broadest and most inclusive patient population ever assembled in a clinical study of Parkinson’s,” Peter Schmidt, the senior vice president of the Parkinson’s Foundation, said in a press release. He has been directing the study.
“This project is truly innovative in that it not only follows thousands of patients over time, but that it studies everyone with Parkinson’s, from the newly diagnosed to people who have lived with the disease for 30 years or more,” added Thomas Davis, the study’s co-chair.
Researchers have been using the Parkinson’s Foundation’s Centers of Excellence network of 42 medical centers to enroll patients in the study.
In addition, “we are studying the quality of Parkinson’s care delivered at our Centers of Excellence to help patients who aren’t being seen at one,” said Fernando Cubillos, who oversees the study’s operations. “Our goal is to help identify the best care and disseminate that information widely.”
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Source:: Parkinson’s Today