Parkinson’s Disease

Parkinson’s disease is a wide problem in many societies. Scientists are making advancement in countering the disease.

Parkinson’s tends to develop gradually and it may be many months, even years, before the symptoms become obvious enough for an individual to visit their GP. A DaTscan is regularly used to help specialists confirm the loss of dopamine-producing cells that cause the development of Parkinson’s.

However, similar loss may also occur in some other rarer neurological conditions. With no molecular test for the condition, diagnosis is made by a neurologist based on a combination of symptoms such as tremor, slowness, stiffness and balance issues. However, many of the symptoms of Parkinson’s can overlap with other conditions, especially in the early stages when progression is gradual and symptoms are more subtle.

In a recent survey of more than 2,000 people with Parkinson’s carried out by Parkinson’s UK, more than a quarter (26 per cent) reported they were misdiagnosed with a different condition before receiving the correct Parkinson’s diagnosis.¹

Scientists move closer to developing ‘game-changing’ test to diagnose Parkinson’s

Results published on March 11, 2021 show it is possible to identify Parkinson’s based on compounds found on the surface of skin. The findings offer hope that a pioneering new test could be developed to diagnose the degenerative condition through a simple and painless skin swab.

Scientists at The University of Manchester have developed a technique, which works by analyzing compounds found in sebum — the oily substance that coats and protects the skin — and identifying changes in people with Parkinson’s Disease. Sebum is rich in lipid-like molecules and is one of the lesser studied biological fluids in the diagnosis of the condition. People with Parkinson’s may produce more sebum than normal — a condition known as seborrhoea.

The research team, led by Professor Perdita Barran, The University of Manchester, and the clinical lead Professor Monty Silverdale at Salford Royal Foundation Trust, recruited 500 people with and without Parkinson’s. Samples of sebum were taken from their upper backs for analysis. Using different mass spectrometry methods, 10 chemical compounds in sebum were identified which are elevated or reduced in people with Parkinson’s. This allows scientists to distinguish people with Parkinson’s with 85 per cent accuracy.

The team confirmed their earlier findings published in ACS Central Science that the volatile compounds on skin can be used to diagnose the condition, increasing the number of people sampled and including participants from the Netherlands, as well as the UK.

In a new study published today in Nature Communications (Eleanor Sinclair, Drupad K. Trivedi, Depanjan Sarkar, Caitlin Walton-Doyle, Joy Milne, Tilo Kunath, Anouk M. Rijs, Rob M. A. de Bie, Royston Goodacre, Monty Silverdale, Perdita Barran. Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-21669-4) high resolution mass spectrometry was used to profile the complex chemical signature in sebum of people with Parkinson’s and show subtle but fundamental changes as the condition progresses. Detailed analysis showed changes in people with Parkinson’s in lipid (fat) processing and mitochondria. Problems with mitochondria — the tiny energy-producing batteries that power cells — are one of the hallmarks of Parkinson’s.

This means this ‘world first’ testing strategy is not only useful in diagnosing Parkinson’s but also in monitoring the development of the condition. The skin swab could provide an incredibly important new tool in clinical trials helping researchers measure whether new, experimental treatments are able to slow, stop or reverse the progression of Parkinson’s.

The study unveiled novel diagnostic sebum-based biomarkers for Parkinson’s, provides insight into understanding of how the condition develops, and links lipid dysregulation to altered mitochondrial function.

These promising results could lead to a definitive test to diagnose Parkinson’s accurately, speedily and cost effectively. The team is now seeking funding to further develop the test and explore the potential for using the test to ‘stratify’ patients.

Working with the University of Manchester Innovation Factory, the team has patents filed for their diagnostic techniques and are planning to create a spin-out company to commercialize the new tests. They are also working to use this approach to develop tests for COVID-19 as shown in research last week in EClinical Medicine as well as other conditions and are actively seeking investors interested in supporting the drive to bring this technology to market.

A report — Rates of Parkinson’s disease are exploding. A common chemical may be to blame — in The Guardian by Adrienne Matei, freelance journalist, said:

Asked about the future of Parkinson’s disease in the U.S., Dr Ray Dorsey says, “We’re on the tip of a very, very large iceberg.”

Dorsey, a neurologist at the University of Rochester Medical Center and author of Ending Parkinson’s Disease, believes a Parkinson’s epidemic is on the horizon. Parkinson’s is already the fastest-growing neurological disorder in the world; in the US, the number of people with Parkinson’s has increased 35% the last 10 years, says Dorsey, and “We think over the next 25 years it will double again.”

Most cases of Parkinson’s disease are considered idiopathic – they lack a clear cause. Yet researchers increasingly believe that one factor is environmental exposure to trichloroethylene (TCE), a chemical compound used in industrial degreasing, dry-cleaning and household products such as some shoe polishes and carpet cleaners.

To date, the clearest evidence around the risk of TCE to human health is derived from workers who are exposed to the chemical in the work-place. A 2008 peer-reviewed study in the Annals of Neurology, for example, found that TCE is “a risk factor for parkinsonism.” And a 2011 study echoed those results, finding “a six-fold increase in the risk of developing Parkinson’s in individuals exposed in the workplace to trichloroethylene (TCE).”

Dr Samuel Goldman of The Parkinson’s Institute in Sunnyvale, California, who co-led the study, which appeared in the Annals of Neurology journal, wrote: “Our study confirms that common environmental contaminants may increase the risk of developing Parkinson’s, which has considerable public health implications.” It was off the back of studies like these that the US Department of Labor issued a guidance on TCE, saying: “The Board recommends […] exposures to carbon disulfide (CS2) and trichloroethylene (TCE) be presumed to cause, contribute, or aggravate Parkinsonism.”

The report, published on April 7, 2021, said:

TCE is a carcinogen linked to renal cell carcinoma, cancers of the cervix, liver, biliary passages, lymphatic system and male breast tissue, and fetal cardiac defects, among other effects. Its known relationship to Parkinson’s may often be overlooked due to the fact that exposure to TCE can predate the disease’s onset by decades. While some people exposed may sicken quickly, others may unknowingly work or live on contaminated sites for most of their lives before developing symptoms of Parkinson’s.

Those near National Priorities List Superfund sites (sites known to be contaminated with hazardous substances such as TCE) are at especially high risk of exposure. Santa Clara county, California, for example, is home not only to Silicon Valley, but 23 superfund sites – the highest concentration in the country. Google Quad Campus sits atop one such site; for several months in 2012 and 2013, the Environmental Protection Agency (EPA) found employees of the company were inhaling unsafe levels of TCE in the form of toxic vapor rising up from the ground beneath their offices.

While some countries heavily regulate TCE (its use is banned in the EU without special authorization) the EPA estimates that 250m lb of the chemical are still used annually in the US, and that in 2017, more than 2m lb of it was released into the environment from industrial sites, contaminating air, soil and water. TCE is currently estimated to be present in about 30% of US groundwater (the non-profit Environmental Working Group created its own map of TCE-contaminated water sites nationwide), though researcher Briana de Miranda, a toxicologist who studies TCE at the University of Alabama at Birmingham School of Medicine, says: “We are under-sampling how many people are exposed to TCE. It’s probably a lot more than we guess.”

Under EPA regulations, it is considered “safe” for TCE to be present in drinking water at a maximum concentration of five parts per billion. In severe cases of contamination, such as that which occurred at Camp Lejeune, a North Carolina marine corps, between the 1950s and late 1980s, people are believed to have been exposed to up to 3,400 times the level of contaminants permitted by safety standards. A memorial site known as “Babyland” honors the children of military personnel who died after they or their pregnant mothers were exposed to TCE-tainted water while living on the base.

While De Miranda says researchers do not believe low concentrations of TCE in drinking water specifically are enough to cause illness, Dorsey does not think it is an overstatement to say US groundwater could be giving people Parkinson’s disease. “Numerous studies have linked well water to Parkinson’s disease, and it’s not just TCE in those cases, it can be pesticides like paraquat, too,” he says, referencing a lethal weedkiller the US still uses despite it being phased out in the EU, Brazil and China.

It said:

Using activated carbon filtration devices (like Brita filters) can help reduce TCE in drinking water, yet bathing in contaminated water, as well as inhaling vapours from toxic groundwater and soil, can be far more difficult to avoid.

De Miranda says policy and effective government intervention are crucial when it comes to testing, monitoring and remediating TCE contaminated sites, and that it’s important to raise awareness of TCE’s role in surging rates of Parkinson’s. Failure to address the issue will not only continue to negatively affect people’s health, but will exacerbate the adult home care crisis that has already left 50 million Americans responsible for providing care to sick loved ones, as Parkinson’s is characterized by slow, progressive degeneration and has no cure.

The report by The Guardian said:

In May 2020, Minnesota became the first state to ban TCE; New York followed suit last December, as should more states, especially as federal action on the issue has lagged. Given the negative health effects of TCE have been documented in the Journal of the American Medical Association since 1932, it is well past time for the US to stop using it, and to better protect its civilians from hazardous chemicals that put lives at risk.

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