Anavex Therapies Reverse Cognitive Defects in Mice, Suggesting Their Use for Parkinson’s

APRIL 13, 2017 BY JOANA FERNANDES, PHD IN NEWS.

Anavex Life Sciences therapies reversed Alzheimer’s-related cognitive deficits in mice and improved processes connected with the disease, according to presentations at an international conference on Alzheimer’s and Parkinson’s.

The presentations at the 13th International Conference on Alzheimer’s & Parkinson’s Diseases dealt with the experimental treatments Anavex 2-73, Anavex 3-71, and Anavex 1-41.

Anavex 2-73, the company’s lead therapy, addresses the misfolded proteins involved in several neurodegenerative diseases. It works by targeting the sigma-1 and muscarinic protein receptors to return cells to a state of equilibrium.  Anavex Life Sciences recently completed a Phase 2a clinical trial of Anavex 2-73 for Alzheimer’s.

In pre-clinical trial studies, Anavex 2-73 showed promise in stopping and reversing Alzheimer’s progression. It also displayed anticonvulsant, anti-amnesic, neuroprotective and anti-depressant properties, suggesting it could be used to treat other diseases, such as epilepsy.

In 2015, the Michael J. Fox Foundation for Parkinson’s Research awarded Anavex Life Sciences a grant to study Anavex 2-73 in an animal model of Parkinson’s.

Another Anavex Life Sciences compound, Anavex 3-71, also targets the sigma-1 and M1 muscarinic receptors. It has shown promise in treating such Alzheimer’s hallmarks as cognitive deficits, accumulation of faulty beta-amyloid and tau proteins, nerve inflammation and defective mitochondrial activity.

Accumulation of the proteins are associated with Alzheimer’s. Mitochondria are cell components that convert food into energy. Their inability to produce enough energy in neurons is associated with neurodegenerative diseases.

Dr. Hélène Hall, a professor at McGill University, gave one of the presentations in Vienna. She said studies in mice with Alzheimer’s showed that Anavex 3-71 reduced inflammatory response in the brain and increased the formation of new contacts, or synapses, between brain neurons. A diminished number of those contacts is a hallmark of Alzheimer’s.

Hall’s study was titled “Targeting M1 Muscarinic And Sigma-1 Receptors In Alzheimer’s Disease: Reversal Of Pathological Hallmarks And Associated Cognitive Dysfunction In Mcgill-R-Thy1-APP Rats.”

Anavex 3-71 also decreased the accumulation of amyloid beta protein and reversed cognitive deficits in mice with Alzheimer’s. The reversal occurred despite the mice having an advanced stage of the disease.

Importantly, the results held after the body eliminated Anavex 3-71, a finding that appears to strengthen its therapeutic potential.

Nino Goguadze of the Université de Montpellier in France made another Anavex presentation. He said studies showed that, when amyloid beta was introduced in mice, Anavex 2-73, Anavex 3-71 and Anavex 1-41 protected mitochondrial activity.

His presentation was titled “The Dual Regulation Of Oxidative Stress By SIGMA1 Receptors In Physiological Or Pathological Conditions.”

“These new results provide converging evidence on mechanism of action as well as possible disease-modifying properties potentially by restoring homeostasis [a state of equilibrium] by means of the sigma-1 receptor agonists in our pipeline,” Christopher U. Missling, Anavex’s CEO, said in a news release. “This data also provides a foundation for our ongoing translational research efforts.”

https://parkinsonsnewstoday.com/2017/04/13/presentations-show-anavex-therapies-reverse-cognitive-deficits-in-mice/

11 Facts About Parkinson’s Disease You May Not Know

APRIL 13, 2017  BY WENDY HENDERSON

 Most people know of Parkinson’s disease and have a good idea of its symptoms, but very few know much more than that about this progressive illness. Since April is Parkinson’s disease awareness month, we’ve put together some simple stats and facts that you can share near and far.

With help from the Parkinson’s Disease Foundation, everydayhealth.com, and ecaring.com, here are 11 facts about the disease most people don’t know. (Some of them may even surprise you!)

It’s a movement disorder. 

Parkinson’s disease is a neurodegenerative disease whereby cells responsible for producing dopamine die off in the substantia nigra area of the brain. Dopamine is essential for movement as it acts as a transmitter for signals from the brain to other parts of the body.

Who found it?

Parkinson’s disease was discovered by British surgeon Dr. James Parkinson in 1817.

How prevalent is it?

Approximately one million people have Parkinson’s disease in the U.S. and there are around 50,000 new cases diagnosed each year.

Most patients are middle-aged. 

The average age of someone diagnosed with Parkinson’s disease is 56. Around 4 percent of Parkinson’s patients are diagnosed before the age of 50 and it’s considered young-onset if diagnosed before the age of 40.

When is it considered young-onset Parkinson’s disease?

It’s considered young-onset if diagnosed before the age of 40. The youngest recorded case of Parkinson’s was a 12-year-old patient.

How is it diagnosed?

There is no blood test or scan that can diagnose Parkinson’s disease. Doctors look for four classic symptoms of the disease before reaching a diagnosis: tremors, rigidity in the wrist and elbow joints, lack or slowness of movement, and an unstable posture.

It affects mostly men. 

Parkinson’s disease is twice as likely to affect men than women.

There’s no known cause. 

There is no known cause of Parkinson’s disease although a family history of the disease will increase your risk. Researchers think environmental factors such as smoking, pollution, heavy metals, medications and illegal drugs may be responsible for the onset of the disease. Head trauma, brain inflammation, and stroke have also been associated with the disease.

Parkinson’s is expensive. 

Treating patients with Parkinson’s disease costs the U.S. around $25 billion a year. The average patient will need $2,500 worth of medication each year and therapeutic surgery could cost up to $100,000.

How do you treat it? 

There is no cure for Parkinson’s disease but there are medications that can help patients with the symptoms. Patients can also undergo deep brain stimulation where electrical current is used to help block tremors and other movement symptoms of the disease.

There’s a correlation between Parkinson’s and depression. 

Dopamine is also associated with mood as well as movement. It’s estimated that more than half of Parkinson’s disease patients suffer from depression and around 40 percent suffer from anxiety.

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.

https://parkinsonsnewstoday.com/2017/04/13/eleven-facts-about-parkinsons-disease/

Minecraft and Tetris could help effects of Parkinson's disease

April 13, 2017

Researchers at Bangor University looking into advantages of computer games

Aaron Pritchard, from BCUHB Research and Development with Dr Charles Leek, Professor of Cognitive Neuroscience at Bangor University’s School of Psychology, and Dr Rudi Coetzer, Consultant Neuropsychologist & Head of Service, BCUHB, and Senior Lecturer in Clinical Neuropsychology, School of Psychology, Bangor University

Computer games such as Minecraft and Tetris could help the effects of Parkinson's disease, according to research by North Wales neuroscientists.

The study is being led by experts at Bangor University, working alongside the Betsi Cadwaladr University Health Board and the Walton Centre in Liverpool. 

They are looking into the the effects of touch screen “spatial reasoning games” on the part of the brain used to control movement in people with Parkinson’s disease.

Tetris is a Soviet tile-matching puzzle video game originally designed and programmed by Alexey Pajitnov. It was released in 1984. Touch screen versions are now available on tablets.

Early research involving 16 people with Parkinson’s suggests computer games, which require users to perform tasks like using mental imagery to rearrange shapes to fit a physical space, could help stimulate one of the impaired areas of the brain affected by Parkinson’s and improve motor function.

Led by Dr Charles Leek, Professor of Cognitive Neuroscience at Bangor University’s School of Psychology, the initial study showed evidence Parkinson’s patients were able to move faster and initiate movement more easily following a period of “cognitive stimulation” on the computer games.

They have now received a £33,000 in funding for a second study involving 60 people with Parkinson’s, which aims to examine the potential benefits of computer-based intervention in greater detail.

Bangor University (Photo: Robert Parry-Jones)

Professor Leek said: "This project was born out of research we completed in 2001, using the School of Psychology’s research dedicated MRI scanner and brain imaging techniques to study how different parts of the brain are involved in controlling our movements and other brain functions.

"We’re trying to apply some of the understanding we have of how the normal brain works to help improve motor control in people with Parkinson’s.

"By having patients perform simple computer based tasks we hope to be able to effectively stimulate specific parts of the brain affected by the disease, which could lead to improved motor function.

"These kinds of tests are incredibly simple and involve people making judgements about visual spatial relationships."

Aaron Pritchard, from BCUHB Research and Development and a co-applicant on the study team said: “There is a wide range of expertise involved in this project. Here in North Wales, we have a long-established portfolio of research into non-drug based interventions for Parkinson’s.

“This project makes a key contribution to helping us better understand the relationship between spatial awareness and movement in Parkinson’s, and how this might be used to develop future therapies.”

Parkinson’s is a degenerative disease of the nervous system characterised by muscle rigidity, tremor, poor balance and slow movement.

http://www.dailypost.co.uk/news/north-wales-news/minecraft-tetris-could-help-effects-12889987

Opportunities and risks of direct-to-consumer genetic health risk tests

April 13, 2017

Accurate genetic testing stands to transform modern medicine by offering effective, personalized treatment. Last week, the U.S. Food and Drug Administration (FDA) authorized marketing of the first direct-to-consumer (DTC) genetic health risk (GHR) tests. Individuals in the US can now purchase DTC tests and gain potentially useful information on their genetic predisposition to 10 diseases or conditions, such as late-onset Alzheimer's or Parkinson's disease.

The stated aim of DTC tests is to help individuals to make decisions about their health and support informed treatment. The FDA authorized tests indicate individual risk of developing conditions like Parkinson's disease, Late-onset Alzheimer's disease, Celiac disease, Alpha-1 antitrypsin deficiency, Early-onset primary dystonia, Factor XI deficiency, Gaucher disease type 1, Glucose-6-Phosphate Dehydrogenase deficiency, Hereditary hemochromatosis, and Hereditary thrombophilia. Individuals will be able to gain direct access to personal genetic risk information by purchasing the kits over the counter. They then send a saliva sample to the company, and after 6-8 weeks receive the results to their inbox.

Despite past concerns about the reliability of DTC tests, the FDA has now approved specific tests for sale as medical devices on the basis of scientific literature that established a link between specific genetic variants and each of the 10 health conditions. Still, they are not "diagnostic" tests, instead the results indicate genetic risk, not whether one has or will develop a disease. The results do not take individual lifestyle factors into account, meaning that their reliability will vary.

THE RIGHT TO KNOW

23andme promotes the tests as "intended to inform users of lifestyle choices and/or encourage conversations with a healthcare professional". Ideally, individuals will make positive health choices based on their results and as a result, general health and wellbeing will improve, thereby bringing down the cost of treatment and insurance. Yet, this premise assumes that we make rational decisions based on available information. An opposing body of research argues that individuals tend not to make decisions based on long-term health. Clearly, we already know that, for instance, eating vegetables and engaging in physical activity are associated with better health outcomes, yet we often go against health advice.

RISKS

Traditionally, genetic tests have only been available through healthcare providers, who should ensure that the individual is provided with adequate support should the results confirm a susceptibility to a particular disease. By cutting out the so-called middle man, individuals affected by their results may have to address the personal ramifications without professional support. Furthermore, individuals may misinterpret a susceptibility to mean that they will develop a particular disease. Another factor is whether individuals will communicate their results to their primary care providers, and whether healthcare professionals are adequately trained to provide tailored medicine based on these results.

Should individuals be able to independently access information on the risk of developing genetic diseases? As the tests do not diagnose an individual with a particular condition, there is a risk that they will needlessly lead to worry and anxiety about a condition that may not develop. A further question is what should we do with information on genetic susceptibility? Could the information that one doesn't carry a genetic risk encourage unhealthy behavior? Indeed, these tests may increase unnecessary doctors' visits, thereby increasing healthcare costs. Further, while one family member may feel they have a right to know, others may not want this type of information. Also, the manner in which family members communicate these risks to each other may cause unintentional distress. However, it should be noted that there is little evidence that DTC genetic tests have long-term negative psychological impacts.

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• New genetic test may give men better view on how to deal with prostate cancer risk
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• Bielefeld University launches five new medical research projects

Still, in 2004, the American College of Medicine Genetics Board of Directors advised against direct to consumer genetic testing:

"Potential harms include inappropriate test utilization, misinterpretation of test results, lack of necessary follow-up, and other adverse consequences"

In 2015, the Board updated its position to encourage minimum requirements for genetic testing such as: adequately accredited laboratories should be used to process the results, a genetics expert should advise consumers on the implications of the results and privacy concerns must be adequately addressed.

Finally, there is a risk that GHR promotes inequity as only those with sufficient means will be able to access the information.

LEGAL PROTECTIONS

US law provides certain protections from discrimination based on genetic information. The Genetic Information Nondiscrimination Act of 2008 (GINA) protects individuals from discrimination on the basis of their genetic information in relation to health insurance and employment. Under GINA, employers are prohibited from refusing to hire, or from firing any employee, or otherwise discriminating due to genetic information. Employees must not be deprived or treated in such a way that would adversely affect their status as an employee.

Also, usually employers cannot request or require genetic information. However, there are certain exceptions, including if health or genetic services are offered as part of a work wellness program. Indeed, Congress is currently considering a bill – the Preserving Employee Wellness Program Act – which would allow employers to penalize employees that don't join workplace wellness programs that collect health and genetic data. As workplace wellness programs are often operated by third parties, there is a risk that such companies may sell employees' genetic data without informed consent. Further, GINA does not apply to life, disability and long-term insurance, although certain states restrict the use of genetic information in determining coverage.

CONCLUSION

Genetic testing is certainly here to stay. Greater genetic awareness and information could encourage patient mobilization and demands for personalized medicine. 23andme is the world's largest bio/databank and individuals are given the option to donate samples. So beyond individual information, research breakthroughs may be on the horizon should individuals choose to donate their samples for further study.

Source:

http://www.law.georgetown.edu/oneillinstitute

http://www.news-medical.net/news/20170413/Opportunities-and-risks-of-direct-to-consumer-genetic-health-risk-tests.aspx

New Simpler Parkinson's Tests Probe Walking, Talking, Typing

April 13, 2017   By Anne Pycha 

The new tests show promise for detecting the neurodegenerative condition earlier

Typing is one of several activities that could help diagnose people with Parkinson’s disease early on. Credit: Getty Images

People with Parkinson’s disease may show hints of motor difficulty years before an official diagnosis, but current methods for detecting early symptoms require clinic visits and highly trained personnel. Three recent studies, however, suggest that diagnosis could be as simple as walking, talking and typing. Tests of activities such as these might eventually enable early intervention, which will be crucial for halting progression of the neurodegenerative condition if a cure becomes available. The findings are exciting, says neurologist Zoltan Mari of Johns Hopkins University. But he cautions that larger studies will be necessary to ensure that these techniques are ready for wider use.

Walking: Data from wearable sensors attached to 93 Parkinson’s patients and 73 healthy controls revealed distinctive walking patterns: factors such as step distance and heel force helped to differentiate between the two groups with 87 percent accuracy, according to an analysis by Shyam Perumal and Ravi Sankar of the University of South Florida.

Talking: In a study by Jan Rusz of Czech Technical University and Charles University, both in Prague, and his colleagues, participants read a list of words aloud, and each made a 90-second recording during which they described their current interests. Fifty of the participants were at high risk for developing Parkinson’s, but only 23 had begun to show symptoms. Simple acoustic features of the short speech samples—including slower speed of talking and longer duration of pauses than healthy controls—pinpointed the symptomatic participants with 70 percent accuracy.

Typing: People with and without Parkinson’s were asked to listen to a folktale and transcribe it by typing. The two groups were matched for age and overall typing speed and excluded people with dementia. Luca Giancardo of the Massachusetts Institute of Technology and his colleagues successfully discriminated between the groups solely by analyzing key hold times (the time required to press and release a key). Their analysis performed comparably or better than motor tests currently used in clinical settings.

https://www.scientificamerican.com/article/new-simpler-parkinsons-tests-probe-walking-talking-typing/

The Michael J. Fox Foundation Announces Five Academic Centers Chosen for 2018-2020 Edmond J. Safra Fellowship in Movement Disorders

April 13, 2017

NEW YORK, April 13, 2017 /PRNewswire-USNewswire/ -- The Michael J. Fox Foundation for Parkinson's Research (MJFF), in collaboration with longtime supporter and partner The Edmond J. Safra Foundation, has chosen five academic centers in the United States and Canada to host the third class of The Edmond J. Safra Fellowship in Movement Disorders.

The centers selected for the 2018-2020 Edmond J. Safra Fellowship in Movement Disorders class are:

University of Alabama at Birmingham

Columbia University Medical Center in New York

Massachusetts General Hospital | Harvard Medical School in Boston

University of Michigan

Toronto Western Hospital in Ontario, Canada

Launched in 2014, The Edmond J. Safra Fellowship in Movement Disorders aims to bridge the gap in funding to train movement disorder specialists — neurologists who have expertise in diagnosing and managing Parkinson's disease. The program is specifically designed to grow the global base of clinician-researcher movement disorder specialists.

"By working with distinguished academic institutions to increase the number of movement disorder specialists, we can ensure people with Parkinson's have access to personalized care from experts at the forefront of research," said Mrs. Lily Safra, chairwoman of The Edmond J. Safra Foundation. "This program will ultimately benefit people with Parkinson's, who will receive remarkable care and have research designed with their interests in mind."

"We are thrilled to again be partnering with The Edmond J. Safra Foundation on this important initiative," said Todd Sherer, PhD, CEO of The Michael J. Fox Foundation. "This program continues to meet a critical need for specialists who can provide individualized patient care and lead research toward disease understanding and therapies to meet patients' needs." 

An advisory committee ranked applicants on several criteria, including the quality of clinical education and the research environment, in order to select the top centers. Each institution will now identify a fellow who will begin two years of training in July 2018.

Patients Informing the Research that Impacts Them
Movement disorder specialist clinician-researchers serve as a link between patients and the research necessary to gain deeper understandings of disease and develop new and better therapies. Regular patient interactions provide these specialists with unique insights into the patient experience and perspective that can directly inform their research projects. The Edmond J. Safra Fellowship in Movement Disorders is helping train experts who can form partnerships with their patients to advance research.

Ongoing Commitment to Parkinson's Research and Care
Late banker and philanthropist Edmond J. Safra's namesake Foundation has long made Parkinson's disease care and research top priorities. Mrs. Safra, chairwoman of the Edmond J. Safra Foundation, has been an MJFF Board member since 2001.

In addition to generous gifts to centers and programs providing direct care to people with Parkinson's disease, Lily Safra and her Foundation have driven vital scientific investigation into new treatments. The fellowship is the latest among many partnerships between the Edmond J. Safra Foundation and MJFF, including the Edmond J. Safra Core Programs for PD Research, one of MJFF's central grantmaking avenues to support high-impact Parkinson's research projects. 

Applications for 2019-2021 Class Opening Soon
 The 2019 Edmond J. Safra Fellowship application will soon be open to academic centers. Please check back on our website for more information and to apply.

About The Michael J. Fox Foundation for Parkinson's Research
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding more than $700 million in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world.

About the Edmond J. Safra Philanthropic Foundation
Edmond J. Safra, one of the 20th century's most accomplished bankers and a devoted philanthropist, established a major philanthropic foundation to ensure that individuals and organizations would continue to receive his assistance and encouragement for many years to come. Under the chairmanship of his beloved wife Lily, the Edmond J. Safra Philanthropic Foundation draws continuing inspiration from its founder's life and values, and supports hundreds of organizations in more than 40 countries around the world. Its work encompasses four areas: Education; Science and Medicine; Religion; and Humanitarian Assistance, Culture and Social Welfare. The Foundation has provided significant funding for Parkinson's disease research and patient care at dozens of hospitals and institutes in places as varied as Natal (Brazil), Toronto, New York, Grenoble, Paris, London and Jerusalem.

For more information, visit www.edmondjsafra.org.

SOURCE The Michael J. Fox Foundation for Parkinson's Research

Related Links

https://www.michaeljfox.org/

http://www.prnewswire.com/news-releases/the-michael-j-fox-foundation-announces-five-academic-centers-chosen-for-2018-2020-edmond-j-safra-fellowship-in-movement-disorders-300439365.html

Brain tissue from a petri dish

April 13, 2017

Scientists at the University of Luxembourg have succeeded in turning human stem cells derived from skin samples into tiny, 3-D, brain-like cultures that behave very similarly to cells in the human midbrain. Credit: © ScienceRelations/University of Luxembourg

The most complex organ in humans is the brain. Due to its complexity and, of course, for ethical reasons, it is extremely difficult to do scientific experiments on it - ones that could help us to understand neurodegenerative diseases like Parkinson's, for example.

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have now succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional, brain-like cultures that behave very similarly to cells in the human midbrain. In the researchers' petri dishes, different cell types develop, connect into a network, exchange signals and produce metabolic products typical of the active brain. "Our cell cultures open new doors to brain research," says Prof. Dr. Jens Schwamborn, in whose LCSB research group Developmental & Cellular Biology the research work was done. "We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated." The team publishes its results today in the prestigious scientific journal Stem Cell Reports.

The human midbrain is of particular interest to Parkinson's researchers: it is the seat of the tissue structure known medically as the substantia nigra. Here, nerve cells - specifically dopaminergic neurons - produce the messenger dopamine. Dopamine is needed to maintain smooth body movements. If the dopaminergic neurons die off, then the person affected develops tremors and muscle rigidity, the distinctive symptoms of Parkinson's disease. For ethical reasons, researchers cannot take cells from the substantia nigra to study them. Research groups around the world are therefore working on cultivating three-dimensional structures of the midbrain in petri dishes. The LCSB team led by stem cell researcher Jens Schwamborn is one such group.

The LCSB scientists worked with so-called induced pluripotent stem cells - stem cells that cannot produce a complete organism, but which can be transformed into all cell types of the human body. The procedures required for converting the stem cells into brain cells were developed by Anna Monzel as part of her doctoral thesis, which she is doing in Schwamborn's group. "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction," Monzel describes her approach. To do this, she was able to draw on extensive preparatory work that had been done in Schwamborn's team the years before. The pluripotent stem cells in the petri dishes multiplied and spread out into a three-dimensional supporting structure - producing tissue-like cell cultures.

"Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed," says Jens Schwamborn. "The cells can transmit and process signals. We were even able to detect dopaminergic cells - just like in the midbrain." This fact makes the LCSB scientists' results of extraordinary interest to Parkinson's researchers worldwide, as Schwamborn stresses: "On our new cell cultures, we can study the mechanisms that lead to Parkinson's much better than was ever the case before. We can test what effects environmental impacts such as pollutants have on the onset of the disease, whether there are new active agents that could possibly relieve the symptoms of Parkinson's - or whether the disease could even be cured from its very cause. We will be performing such investigations next."

The development of the brain-like tissue cultures not only opens doors to new research approaches. It can also help to reduce the amount of animal testing in brain research. The cell cultures in the petri dishes are of human origin, and in some aspects resemble human brains more than the brains of lab animals such as rats or mice do. Therefore, the structures of human brains and its modes of function can be modelled in different ways than it is possible in animals. "There are also attractive economic opportunities in our approach," Jens Schwamborn explains: "The production of tissue cultures is highly elaborate. In the scope of our spin-off Braingineering Technologies Sarl, we will be developing technologies by which we can provide the cultures for a fee to other labs or the pharmaceutical industry for their research."

More information: Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2017.03.010 

Journal reference: Stem Cell Reports

Provided by: University of Luxembourg 

https://medicalxpress.com/news/2017-04-brain-tissue-petri-dish.html

Researchers identify link between birth defect and neurodegenerative diseases

April 10, 2017

Credit: axelle b/public domain

A new study has found a link between neurological birth defects in infants commonly found in pregnant women with diabetes and several neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases. 

This is the first time this link has been identified; it may indicate a new way to understand, and perhaps treat, both neural tube defects and these neurodegenerative diseases.The findings will be published Monday in the Proceedings of the National Academy of Sciences.

"These results were really surprising," said the study's lead author, Zhiyong Zhao, PhD, a researcher at the University of Maryland School of Medicine (UM SOM). "The association suggests that these disparate diseases may have more in common than we previously realized." The researchers on the article also include UM SOM Dean E. Albert Reece.

Neural tube defects occur when misfolded proteins accumulate in the cells of the developing nervous system. The misfolded proteins form insoluble clumps and cause widespread cell death, eventually leading to birth defects. Protein clumps also play a major role in Alzheimer's, Parkinson's and Huntington's disease. In Alzheimer's, for instance, this leads to the accumulation of plaques in the brain, reducing the ability of that organ to function.

The researchers studied pregnant mice with diabetes, and found that their embryos contained clumps of at least three misfolded proteins that are also associated with the three neurodegenerative diseases: α-Synuclein, Parkin, and Huntingtin. It is not clear exactly how these protein clumps contribute to those diseases, but the link is well established.

This latest research also underscores the links between diabetes and some neurodegenerative diseases. People with diabetes have a higher risk of Alzheimer's and Parkinson's disease, and some research suggests that there are molecular links between Huntington's and diabetes as well.

The scientists also examined whether it is possible to reduce levels of the misfolded proteins, and in so doing reduce neural tube defects. They gave diabetic pregnant animals sodium 4-phenylbutyrate (PBA), a compound that can reduce mistakes in molecular structure by aiding the molecules that ensure proper protein folding. In the animals that received PBA, there was significantly less protein misfolding, and fewer neural tube defects in the embryos. PBA has already been approved by the US Food and Drug Administration for other uses, and if it proves safe and effective in humans for this purpose, it could potentially reach patients much more quickly than an entirely new drug.

Neural tube defects are birth defects of the brain and spinal cord. They occur in the first month of pregnancy. The two most common are spina bifida and anencephaly. In the first, the fetal spinal column doesn't close completely. This usually causes nerve damage, with some paralysis of the legs. In the latter, most of the brain and skull do not develop. Infants with this defect are usually stillborn or die soon after birth. Neural tube defects have several causes, including diabetes, folic acid deficiency, obesity in the mother, and consumption of certain medications. About 10 percent of women with diabetes who are pregnant will have embryos with neural tube defects.

More information: Formation of neurodegenerative aggresome and death-inducing signaling complex in maternal diabetes-induced neural tube defects, Proceedings of the National Academy of Sciences (2017). www.pnas.org/cgi/doi/10.1073/pnas.1616119114

Journal reference: Proceedings of the National Academy of Sciences

Provided by: University of Maryland School of Medicine

https://medicalxpress.com/news/2017-04-link-birth-defect-neurodegenerative-diseases.html