International Group Reflects on Decade Of Collaborative Parkinson’s Genetics Research, Notes Future Plans

IPDGC progress, future

A decade after its founding, the International Parkinson Disease Genomics Consortium (IPDGC) is looking back on on its first 10 years of research and outlining its goals for the future.

IPDGC was started in 2009 by a small group of researchers who thought that collaborative efforts were necessary to further understanding of the genetics of Parkinson’s disease (PD).

The group has now published a paper, titled “Ten Years of the International Parkinson Disease Genomics Consortium: Progress and Next Steps,” in the Journal of Parkinson’s Disease, in which they reflect on the progress they’ve made and where they hope to go from here.

It has long been thought that genetics might play a role in Parkinson’s, and this question has been the subject of much research. In the early 2000s, this field was extremely competitive and not very collaborative.

“The stakes were high, there was little reward for second place … and there was little mechanism for shared success,” the researchers wrote.

Beginning around 2005, however, technological advancements and initiatives such as the Human Genome Project started to facilitate genetic research with data on a scope and scale that had not been possible before. Critically, the more data available for these analyses, the more powerful they are — and as such, there was a strong need for data-sharing and collaboration.

“The IPDGC was born out of a realization that no single investigator could deliver on the promise of modern human genetics in isolation,” co-author Andrew Singleton, PhD, of the National Institutes of Health, said in a press release. “We realized that to truly leverage the incredible gains in genetic technologies in the PD space, at scale, would require a highly collaborative approach.”

IPDGC was the result of a 2009 meeting that included about 10 researchers in Paris. Since then, the group has grown to more than 100 researchers around the world. They hold annual meetings, and recently started new research initiatives in Africa and the Middle East — most of their research to date has focused on populations in Europe and the U.S.

“The coordinated analysis of genome-wide association (GWA) data was perhaps the first success for IPDGC and has continued to be a mainstay of our work,” Singleton said.

GWA involves looking for genetic variations that tend to be associated with a particular condition — in this case, Parkinson’s. The IPDGC has performed GWA studies using data its researchers have collected as well as data from industry collaborators such as 23andMe.

While the first of these efforts only included about 3,000 people, the most recent study had data for more than 50,000 people with Parkinson’s, as well as roughly 1.4 million people used as controls.

“As in other disorders, as sample size has grown, so has power and the number of loci detected,” the researchers wrote. “Currently, there are more than 90 known risk loci for [Parkinson’s].” (Loci are positions on a chromosome where a particular gene or genetic marker is located.)

Beyond the identification of risk loci, collaborations fostered by the IPDGC have also helped in understanding the biological processes underlying Parkinson’s disease. For example, such research revealed that Parkinson’s is associated with changes in the tissue of the brain itself, particularly in the cells of a region called the substantia nigra. This contrasts with Alzheimer’s disease, where similar dysregulation is typically seen in immune cells, not the brain cells themselves.

IPDGC’s research has also led to the discovery and validation of previously unknown pathways associated with the disease, and how mutations in these pathways can affect disease risk, such as how mutations in the VPS13C gene can be a cause of early-onset Parkinson’s disease.

This research has also contributed to the estimation that 16–36% of Parkinson’s risk has some kind of genetic basis.

Future work anticipated by the IPDGC includes more research to better understand the genomic architecture of Parkinson’s, particularly in groups of non-European descent, which have historically been understudied. This also involves more detailed studies looking for links between genetic variations and particular aspects of how Parkinson’s manifests from person to person.

The group also hopes to continue to facilitate efforts to build larger research cohorts and to share data and resources among researchers. For instance, one tool in development is the IPDGC sequencing browser, which allows users to look at sequence information for IPDGC data. Another, the IPDGC GWAS browser, is a community-driven site aimed at identifying previously unknown Parkinson’s genes.

“While we believe the work of the IPDGC has had a significant and lasting impact on our field over the last ten years, we are even more excited by the course we have charted for the next decade,” Singleton said.

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Pesticides and Head Injuries – But Also Nuts, Red Meat and Soft Drinks – Linked to Parkinson’s Risk in Cyprus Study

diet and disease risk

Exposure to pesticides, severe head injury with fainting, and consumption of soda, nuts and red meat appear to be risk factors for Parkinson’s disease among people in Cyprus, a Mediterranean island with an interesting genetic mix, a study suggests.

Study results further suggest that smoking and eating fish are associated with a lower risk of Parkinson’s, and it confirms some previous findings of genetic associations with the disease.

Genetic and Environmental Factors Contributing to Parkinson’s Disease: A Case-Control Study in the Cypriot Population” was published in Frontiers in Neurology.

It is well-established that both environmental and genetic factors contribute to an individual’s risk of Parkinson’s disease (PD), and many studies have looked for associations between these factors and the disease to determine what specific factors increase or decrease Parkinson’s risk.

Researchers here focused on people of Greek-Cypriot ethnicity living on Cyprus.

“[Cyprus] is a crossroad between Africa, Europe and Middle East. This made Cyprus a ‘genetic pool’ for transiting populations … characterized by genetic affinity with surrounding Southeast European and Near Eastern populations … [and] renders genetic studies in the Cypriot population informative for the genetically similar populations as well,” the researchers wrote.

They also investigated environmental factors for PD within Cypriot population, some of which “are of high prevalence,” and compared them with studies in populations elsewhere.

The researchers collected data — including medical histories, lifestyle factors, etc. — from 235 Cypriot people with Parkinson’s and 464 people without it as controls. There was a roughly even mix of males and females in both groups.

The Parkinson’s group was older than the control group (average age 70 vs. 64.5), had a significantly greater proportion of retired people (86% vs. 60.9%), and had a significantly lower body mass index (BMI).

Researchers created statistical models, which accounted for some of these inherent differences, to identify lifestyle and other factors relevant to a risk association.

They found that more frequently eating nuts and red meat, as well as consuming soft drinks more often, were associated with an increase in Parkinson’s risk of about two-fold (2.74 for nuts, 1.92 for meat, and 2.06 for soft drinks).

“PD cases had a significantly lower adherence to ‘healthy eating’ when compared to controls,” the researchers wrote.

They suggested the link with nuts might be due to pesticides accumulating in the nuts themselves or in the soil of trees they grow on.

“This is the first study detecting an increased risk for PD for moderate and heavy soft drinks consumers,” the researchers wrote. “A possible explanation could be given by a rat model study which demonstrated that carbonated soft drinks induced oxidative stress and also altered the expression of certain genes associated with brain activity.” But because soft drinks come in so many varieties, it’s “challenging to trace the component that could potentially cause neurodegeneration.”

Severe head injury with fainting was associated with a 2.42 times greater risk of Parkinson’s disease, and exposure to pesticides and other toxic substances with a 3.28-times higher risk.

Eating fish and smoking were both linked with about a three times lower chance of Parkinson’s (0.39- and 0.32-fold risk, respectively). Notably, coffee consumption was not analyzed as a predictor of Parkinson’s in this population, though the researchers noted that coffee consumption and smoking were closely linked with each other.

The researchers also looked at 13 gene mutations linked to Parkinson’s in previous studies. In this patient group, five of these variants were significantly associated with Parkinson’s in the same directions as previously reported. The variants rs12185268 in the SPPL2C  gene and rs17649553 in the MAPT gene — which provides instructions to make the tau protein — were linked with a lower Parkinson’s risk, while the variants rs13312 in USP24, rs6599389 in TMEM175, and rs356220 in SCNA — which provides instructions to make the alpha-synuclein protein — were associated with a greater risk.

“In conclusion,” the researchers wrote, “the current study has demonstrated a number of genetic and environmental predictors for PD [Parkinson’s disease] in the Cypriot population.”

“[E]xposure to both pesticides and other toxic substances, severe head injury accompanied with fainting, nuts consumption, red meat consumption, and soft drinks consumption were predisposing factors, whereas cumulative smoking and fish consumption were protective factors for PD risk. The association between [several gene mutations] and PD risk was replicated in the Cypriot population.”

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Genetic Parkinson’s More Common Than Thought, Global Survey Reveals

Genetic PD survey

Cases of inherited Parkinson’s disease may be more frequent than previously reported, results from an online global survey suggest.

The survey, which was conducted by members of The Michael J. Fox Foundation Global Genetic Parkinson’s Study Group (MJFF-GGPSG), also revealed the willingness of investigators to share clinical information on their patients that could be useful to conduct broader and more inclusive studies.

These findings suggest it is necessary to improve the way investigators communicate and assess clinical data. It also highlights the need of new integrative research approaches that can empower teams to enhance the understanding and recognition of genetic mutations contributing to the development of Parkinson’s disease. This could be an important step to improve early diagnosis and define preventive strategies.

The results, “Identifying genetic Parkinson’s disease patients worldwide: Exploiting novel ways of team science,” were presented as a scientific poster during the International Congress of Parkinson’s Disease and Movement Disorders in Nice, France.

“This initiative is of high relevance because it is becoming increasingly clear that even relatively common diseases like Parkinson’s disease are highly etiologically heterogeneous syndromes and that progress towards early diagnosis and causative treatments will depend on the identification of sufficient numbers of well-defined subgroups,” Thomas Gasser, MD, said in a press release. Gasser is director of the department of neurodegeneration at Hertie Institute for Clinical Brain Research, in Tuebingen, Germany.

“This will only be possible by collaborations at a very large, preferably worldwide scale,” he said.

The survey, which was conducted in 2018, was designed to evaluate the availability of demographic, clinical, genetic, and additional data of patients with genetic Parkinson’s disease. It included cases caused by SNCA, LRRK2, VPS35, PRKN, PINK1, PARK7, and GBA mutations.

MJFF-GGPSG researchers addressed the survey to 336 investigators who were selected based on articles that had been published about the subject and were represented at the Movement Disorder Society Genetic mutation database (MDSGene), and through the Genetic Epidemiology of Parkinson’s disease (GEoPD) consortium.

Of the 336 investigators invited to participate in the survey, 162 (48%) responded, 98% of whom indicated interest in further collaboration.

“The overwhelmingly positive response and willingness to collaborate impressively highlight the relevance and power of team science,” the researchers wrote.

Researchers reported information from a total of 8,453 Parkinson’s patients with genetic mutations; more than nine different ethnicities were followed at 103 international sites across 43 countries.

Overall, mutations in the SNCA, VPS35, PINK1, and PARK7 genes were present in 3% (263 patients), 0.4% (35 patients), 3% (260 patients) and 0.3% (29 patients) of this patient population.

The most commonly affected genes were LRRK2, GBA, and PRKN, with mutations present in 38% (3,182 patients), 37% (3,154 patients), and 18% (1,530 patients).

These frequencies are particularly significant given that they represent a threefold higher number of patients with mutations associated with Parkinson’s disease when compared to the cases reported in the literature.

More than 98% of investigators who responded to the survey noted they had demographic data on their patients, with 94% of them having age-at-onset information, and only 66% reported having information on patients’ non-motor signs.

Most investigators (85%) had DNA samples from the patients, while only 8% had cerebrospinal fluid (CSF) samples. (CSF is the liquid that surrounds the brain and spinal cord.)

“This survey is only a very first small step. If international team science is to become successful, many problems concerning standardization of patient ascertainment, data privacy and protection as well as data access and use need to be solved,” Gasser said.

“Nevertheless, the survey raises awareness of these issues and it clearly shows that the Parkinson’s disease research community is ready to begin to tackle these important issues,” he said.

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Fox Foundation Awards $5M to Support Genetic Studies of Parkinson’s in Africa, Asia and India

Fox Foundation grant

With the overarching goal of helping scientists develop and test targeted therapies in Parkinson’s (PD), The Michael J. Fox Foundation (MJFF) is awarding $5 million in grants to three teams conducting genetic studies in African, East Asian and Indian populations.

The funding seeks to broaden these studies in order to better understand the role of genetics in PD onset and progression, and to expand treatment options for patients globally. Historically, the majority of research has focused on people of European descent. The grants will enable genetic testing of samples from more than 30,000 people.

“While the field has made significant strides in genetic research, we know we have more to learn about the changes in DNA that lead to Parkinson’s disease and impact its progression,” Brian Fiske, PhD, MJFF senior vice president of research programs, said a news release. “This is an all-star initiative with world-class geneticists, clinic networks and study volunteers coming together to paint a global picture of Parkinson’s and work toward cures for everyone.”

Since researchers discovered the first genetic mutation linked to PD in 1997, more than 80 others have been identified. Scientists are studying the cellular impact of these mutations, associated with about 15 percent of PD cases, in order to better understand Parkinson’s and possible ways of treating it.

Potential therapies aimed at proteins including LRRK2, one of the most commonly known genetic causes of Parkinson’s, are in clinical trials. Work like this is what the global Parkinson’s genetics program hopes to build upon. The non-profit foundation has long backed genetic studies, and diversity and inclusivity in clinical investigations.

Grants under this global program — with support from the Edmond J. Safra Foundation, a long-time partner of the Fox Foundation — will go to the following projects:

“Parkinson’s is a global issue, and we are grateful to The Michael J. Fox Foundation for fostering representation in research,” said Njideka Okubadejo, a professor of research at the University of Lagos in Nigeria. “We hope this partnership results in greater understanding of disease causes and contributors, and leads to new treatments for people living in Africa and beyond.”

Parkinson’s is the second most common age-related neurodegenerative disorder (after Alzheimer’s), and estimated to affect 7 to 10 million people worldwide.

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Migraines, OCD, and Seasonal Allergies May be Risk Factors for Parkinson’s, Large Study Suggests

Parkinson's traits

Migraines, obsessive-compulsive disorder, and seasonal allergies seem to be associated with Parkinson’s disease and are likely to occur many years before the typical age of diagnosis, a large study has found.

Results of the study, “The Parkinson’s phenome—traits associated with Parkinson’s disease in a broadly phenotyped cohort,” were published in the journal npj Parkinson’s Disease.

Trying to identify the factors that influence whether a person will develop Parkinson’s disease is not a new idea. However, because Parkinson’s is a rare disease, such studies often don’t have enough participants to be sure that associations are real and not the result of chance.

To try to get around this problem, researchers behind a new study analyzed data from 13,546 Parkinson’s patients and more than one million control subjects to find traits associated with Parkinson’s development.

The team primarily used data from customers of 23andMe — a web-based company that provides genetic testing and analysis — who consented to be included in the study, and from surveys sent to and filled by various Parkinson’s patient groups.

After amassing the data, the researchers set about finding the factors — including family history, other diagnoses, environmental factors, personality traits, and medication usage — that were correlated with developing Parkinson’s.

The team analyzed 832 traits individually, since not every patient had data for every trait. This resulted in a list of a few hundred traits that showed some evidence of an association with Parkinson’s. The researchers then applied statistical tests and corrected for factors such as education and income, and ended up with 122 traits that were significantly associated with the disease, including some previously known factors. For example, people who consumed a lot of caffeine were less likely to have Parkinson’s, and those with the disease were more likely to report experiencing constipation.

The researchers also identified 42 traits that had not previously been associated with Parkinson’s. For example, those who could wiggle their ears or whistle were less likely to have the disease, whereas Parkinson’s patients were more likely to be afraid of heights, be farsighted, have seasonal allergies, and be married.

This large study was able to shed light on associations that had been suggested but for which there hadn’t been large enough sample sizes to draw a definitive connection. For example, the investigators found that those with obsessive-compulsive disorder (OCD) were more likely to develop Parkinson’s, supporting previous studies that were too small to achieve significance.

Although previous studies have yielded non-significant results due to their small sample sizes, “with 10,437 (Parkinson’s) cases in this particular regression, our study was well-powered to detect a positive association between (Parkinson’s) and OCD,” the researchers stated.

In addition, they found a significant association between Parkinson’s and migraines.

“We observed that migraine was positively associated with (Parkinson’s),” they said. “Only two cohort studies have previously been conducted, but both found that midlife migraine was associated with increased risk of (Parkinson’s disease) …. Since the average age of onset is typically much earlier for migraine than for (Parkinson’s), migraine may be a novel (Parkinson’s) risk factor.”

While previous studies have shown that Parkinson’s was positively associated with allergic rhinitis, but not asthma or hayfever, the current study found that it was also associated with allergies to plants and antibiotics, but not with allergies to food or animals.

“Understanding the biological differences between these different groups of allergies may allow us to hone in on specific immunological pathways that contribute to (Parkinson’s) risk,” the researchers said. “Seasonal allergies typically develop early in life, but further research is needed to determine whether having seasonal allergies is a risk factor for (Parkinson’s). If so, it may be possible to manipulate risk using immune-modulating drugs.”

The researchers noted that their study showed correlations, and not causation — that one thing does not necessarily cause another because the two are correlated. For example, people with Parkinson’s tend to report being more introverted, but it’s highly debatable whether the factors that make a person introverted also predispose them to Parkinson’s or if people with Parkinson’s are more likely to become introverted due to the difficulties of living with a neurodegenerative disease.

Similarly, marital status doesn’t seem likely to influence the development of Parkinson’s, although the researchers noted that spouses may notice sleep disturbances, which could increase the chances of people eventually getting diagnosed. At this point, however, these ideas are largely speculation.

Still, this study is not without value: “Now that we have identified phenotypes (traits) that are correlated with (Parkinson’s) it is also possible to test whether these phenotypes are causes or consequences of the disease,” the investigators wrote, adding that even in the absence of a known causal relationship, “phenotypes that are correlated with (Parkinson’s) can be used to predict (the disease) as long as the phenotype is enriched in (Parkinson’s disease) cases prior to diagnosis.”

In other words, having the data about factors that are associated with Parkinson’s can be a starting point for further research. It could be used to make predictions about Parkinson’s patients, particularly through the use of computer models and machine learning, which can interpret these massive datasets more efficiently than people.

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Genetic Variant Predetermines Risk of Cognitive Decline in Parkinson’s, Research Suggests

genetic variant

Researchers have found that Parkinson’s patients whose cognitive ability is intact, but who have a specific genetic variant, have significantly less gray matter in the regions of their brain that are related to dementia.

The study with that finding, “Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson’s disease patients and its association with cognitive decline,” was published in Brain Imaging and Behavior.

Several mutations in the COMT gene have been associated with the risk of developing Parkinson’s disease. This gene provides instructions for making catechol-O-methyltransferase (COMT), an enzyme that helps break down certain chemical messengers like dopamine.

The most common alteration in the DNA sequence that makes up the COMT gene is the Val158Met mutation in which a valine (Val) is replaced by a methionine (Met) at position 158. Val and Met are both amino acids, also known as the protein’s building blocks.

Every individual has two copies of each gene, one inherited from each parent. Therefore, a person can have two Val’s in the same position at both COMT gene copies (also known as the Val/Val genotype), a Val in one gene and a Met in the other (Val/Met genotype), or two Met’s (Met/Met genotype). Scientists use the word “genotype” to describe a person’s genetic constitution.

Changes in COMT’s molecular structure, lead to high (Val/Val), intermediate (Val/Met) and low (Met/Met) enzymatic activity.

The Val158Met mutation in the COMT gene has been associated with an increased risk of cognitive decline in Parkinson’s disease, particularly in people with greater COMT activity. When this happens, there is too much neurotransmitter degradation, thus leading to reduced levels of dopamine and affecting basic brain functions such as motor coordination and memory.

Evidence suggests a correlation between cognitive impairment, one of Parkinson’s non-motor features, and reduced gray matter volume.

The brain is composed of gray and white matter. The first consists of cell bodies — the control center of neurons — while the latter is made up of nerve cell projections, known as axons or fibers, connecting distinct parts of gray matter.

A Spanish team of researchers used magnetic resonance imaging (MRI), a non-invasive imaging technology, to investigate a possible structural brain compromise in Parkinson’s patients with highly active COMT activity that could explain their increased risk for subsequent cognitive impairment.

The study included 120 newly diagnosed Parkinson’s patients with normal cognition (who were not previously treated for the disease) and 48 healthy controls from the Parkinson’s Progression Markers Initiative database.

Results showed that there was a widespread, significant reduction in cerebral gray matter volume in patients with the Val/Val genotype. They observed alterations in the fronto-subcortical and posterior-cortical brain regions, where motor and cognitive functions originate.

Gray matter volume at some of the identified regions was associated with cognitive decline in a four-year follow-up period, suggesting that gray matter volume reduction during the early stages of disease predisposes Val/Val patients to cognitive impairment.

Nonetheless, gray matter volume analysis at one-year follow-up was not increased in Val/Val subjects, in comparison to Val/Met and Met/Met participants, indicating a somewhat stable atrophy in the Val/Val subset and that those brain changes might already be present prior to diagnosis.

The team believes their research “sparks the need to further characterize the association between a modified COMT enzymatic effect and a structural brain compromise in the early stages of [Parkinson’s disease].”

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First-degree Relatives at Higher Risk of Parkinson’s, Other Neuropsychiatric Disorders, Study Finds

first-degree relatives risk

First-degree relatives of Parkinson’s patients are more likely to develop the disease and are at a higher risk for other neuropsychiatric disorders, a study shows.

The study, “Familial aggregation of Parkinson’s disease and coaggregation with neuropsychiatric diseases: a population-based cohort study,” was published in Clinical Epidemiology.

Most Parkinson’s cases are considered to be sporadic, but several studies have suggested that the disease results from a combination of genetic and environmental factors.

Several genes have been pinpointed as the cause of 6 to 7 percent of the clinical variability observed in Parkinson’s disease.

To better understand the impact of genetic and environmental factors on the development of Parkinson’s, researchers reviewed potential risk factors that could be linked to familial aggregation of the disease.

Clinical records of all individuals registered in the Taiwan National Health Insurance Research Database in 2015 were analyzed. Of the total registered population of 24,349,599 individuals, 112,037 were diagnosed with Parkinson’s disease.

This included 149,187 individuals who had a parent affected by Parkinson’s, 3,698 with an affected offspring, 3,495 with an affected sibling, and 15 individuals with an affected twin.

Researchers found that individuals who had a first-degree relative with Parkinson’s disease had a 1.69 times increased chance of also developing the disease. This risk was similar for both male and female relatives and was greater for twins, who were 63.12 times more likely to develop Parkinson’s.

The risk of developing Parkinson’s was 2.2 times higher for siblings, 1.86 times higher for offspring, 1.59 times higher for parents, and 1.46 times higher for spouses.

These results suggest that the clinical variability of Parkinson’s prevalence observed in the Taiwanese population is accounted for by genetic factors (heritability) at 11%, shared environmental factors at 9.1%, and non-shared environmental factors at 79.9%.

Additional analysis further showed that first-degree relatives of Parkinson’s patients are also at an increased risk for some other neuropsychiatric disorders than the general population. These include major depression, anxiety, multiple sclerosisAlzheimer’s disease, and amyotrophic lateral sclerosis, among others.

Researchers believe that Parkinson’s disease “should be considered an age-related multifactorial syndrome with mainly genetic and environmental components.”

“First-degree relatives of PD patients are more likely to develop PD and other neuropsychiatric diseases. Environmental factors account for a high proportion of the pheno- typic variance of PD,” they wrote.

“Our findings provide information useful for counseling families of Parkinson’s patients,” they also said.

Additional studies are still needed to identify the environmental causes responsible for Parkinson’s susceptibility, and the genetic contribution for disease variability remains to be determined in other populations.

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‘PATH to PD’ Program Seeks to Deepen Understanding of Parkinson’s Onset, Progression

Michael J. Fox Foundation

The Michael J. Fox Foundation for Parkinson’s Research (MJFF) will fund a new program to investigate the pathogenesis of Parkinson’s disease called “PATH to PD.”

The two-year program includes three research teams that will collaborate to investigate risks associated with genetics, environment and aging, while working with a common framework to gain a better understanding of the onset and progression of Parkinson’s.

Each PATH to PD-funded project will receive $2 million.

“The vast diversity of pathways implicated in Parkinson’s pathology to date indicates that multiple physiological routes can lead to PD, and these routes may intersect or be temporally dependent,” Todd Sherer, PhD, CEO of MJFF, said in a press release. “Through PATH to PD, our Foundation aims to encourage researchers to bring a holistic new approach to bear on refining today’s understanding of what Parkinson’s is — so that we can better strategize how to slow or stop the disease.”

Parkinson’s is not fully understood by scientists. Even though it is known the disease stems from gene-environment interactions as we age, the emerging picture of Parkinson’s is that of a vast, interwoven network culminating in a disease that varies greatly in cause, rate of progression, symptomology and treatment response.

All three teams will collaborate to build a common framework linking mechanisms through which genetics, environment and aging-associated risk and causal factors may lead to Parkinson’s disease.

University of Pittsburgh researchers, led by J. Timothy Greenamyre, MD, PhD, will seek out links between environmental and genetic triggers of the disease. Researchers will look into the mechanisms that lead neurotoxins to cause neurodegeneration and how these pathways are involved in interactions with genetic factors such as LRRK2 (leucine-rich repeat kinase 2), the leading genetic cause of the disease.

National Institutes of Health researchers, led by Andrew Singleton, PhD, will map the genetic effects in Parkinson’s by growing nerve cells from induced pluripotent stem cells, and map how various genetic alterations lead to the molecular and cellular changes associated with Parkinson’s.

Northwestern University researchers, led by D. James Surmeier, PhD, will investigate the link between aging and Parkinson’s. Using advanced gene-editing techniques, they will look at how cellular aging and related DNA and mitochondrial damage contribute to neurodegeneration in rodent and human cells.

These efforts have the common goal of developing a disease-modifying treatment for Parkinson’s disease, so that it can stop or slow disease progression.

For disease-modifying treatments to work best, however, they should target key underlying disease-causing pathways, which need to be identified and isolated first.

Some cases of Parkinson’s occur due to genetic factors, known as familial Parkinson’s disease. However, familial Parkinson’s is only a small fraction of all diagnoses of the disease. Informed guesses lean toward  environmental factors, including heavy metal or pesticide exposure, since aging still accounts for the greatest risk factor underlying this disease.

The fact that there is no identifiable cause of immediate contamination, researchers suspect this might be due to a lifetime accumulation of otherwise minor compound exposures that eventually lead to the development of the disease or contribute to a “switch” in Parkinson’s risk genes. Perhaps the process occurs naturally as medicine allows us to live longer, or perhaps it’s a combination of both.

“With Parkinson’s prevalence expected to double by 2040 to nearly 13 million people worldwide, our Foundation believes it is our obligation to continue building on current research momentum to eradicate this disease once and for all,” Sherer added.

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4 Possible Causes of Parkinson’s Disease

While the exact cause of Parkinson’s disease is currently unknown, scientists have come up with four possible theories according to the Mayo Clinic.

1. Genetics
There are certain genes which, when they become mutated, cause Parkinson’s disease. However, these mutated genes are very rare, except in cases where Parkinson’s runs in the family. There are also some gene variations which seem to slightly increase the risk of developing Parkinson’s.

MORE: Seven ways to help you self-manage Parkinson’s disease

2. Environment
Researchers think that there are some environmental factors and toxins which may trigger Parkinson’s disease, although they feel the increased risk is small.

3. Presence of Lewy bodies
Changes happening within the brain may also be a trigger for Parkinson’s disease. Lewy bodies are proteins found in brain cells which are biomarkers of the disease and may hold the key to finding out the exact cause.

4. Alpha-synuclein in Lewy bodies
There are many different substances found in Lewy bodies, but scientists are focusing on alpha-synuclein proteins. Alpha-synuclein proteins don’t break down; they form clumps in the cells which are thought to contribute to the disease.

MORE: The role of dopamine in the development of Parkinson’s disease

Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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