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VANQUISH
Schizophrenia causes discovered Bipolar Disorder ‡ Linked to childhood adversity ‡ Associated with high blood pressure medication Paranoia Reduction with virtual reality Alzheimer’s Disease ‡ Potential treatment ‡ Prevention Parkinson’s Disease Discovery of new cure
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SC H I Z O PH R E NIA
Schizophrenia breakthrough: scientists shed light on biological cause
People with bipolar disorder more than twice as likely to have suffered childhood adversity
What causes schizophrenia? This is a question that has challenged scientists since the disorder was first identified almost 130 years ago. Now, for the first time, researchers have shed light on the biological origin of the illness.
‡ Better understanding of risk factors that can be used to improve detection and treatment urgently needed. ‡ People with bipolar disorder are 2.63 times more likely to have suffered emotional, physical or sexual abuse as children.
Honor Whiteman
The University of Manchester
In what has been hailed a “breakthrough” in schizophrenia research, scientists from Harvard Medical School, the Broad Institute and Boston Children’s Hospital - all in Massachusetts - have discovered how a gene called complement component 4 (C4) plays a key role in schizophrenia development. The research team - including senior author Steven McCarroll, associate professor of genetics and director of genetics for the Stanley Center at Harvard - says their findings may aid the development of much-needed new treatments and preventive strategies for schizophrenia. Schizophrenia is a mental disorder characterized by hallucinations, delusions, dysfunctional thought processes and agitated body movements. It is estimated that around 21 million people across the globe have schizophrenia, with symptom onset most common in late adolescence or early adulthood. The illness was first discovered by German psychiatrist Dr. Emile Kraepelin in 1887, though the term “schizophrenia” was not used until 1910, coined by Swiss psychiatrist Paul Eugen Bleuler. The name came from the Greek words “schizo” (split) and “phren” (mind), fueling the myth that people with schizophrenia have split personalities; this is not the case.
Understanding the genetic roots of schizophrenia In the years since schizophrenia was discovered, researchers have been working hard to determine the underlying biological mechanisms that cause the illness. Lack of understanding in this area has hampered the discovery of a cure or preventive strategies for schizophrenia; current treatments such as antipsychotic medications - can only focus on eliminating symptoms. Increasingly, researchers have looked at how schizophrenia may be caused by genetic factors, based on the knowledge that the disorder is heritable. In July 2014, the Schizophrenia Working Group of the Psychiatric Genomics Consortium - including investigators from the Stanley Center - identified more than 100 areas of the human genome that are linked to the disorder. Now, McCarroll and colleagues have built on these findings, identifying a specific gene that appears to have the strongest association with schizophrenia risk. This gene is C4, which is already known to play a key role in the immune system, alerting immune cells to pathogens that need to be destroyed.
Specific C4 structures linked to increased schizophrenia risk For their study, recently published in the journal Nature, the team set out to gain a better understanding of how C4 works in the brain. McCarroll and his colleague Aswin Sekar, an MD/ PhD student at Harvard Medical School, created a novel molecular technique that enabled the team to characterize the structure of the C4 gene in the DNA samples of more than 65,000 individuals, of whom around 29,000 had schizophrenia and 36,000 did not. Additionally, the researchers analyzed C4 activity in almost 700 post-mortem brain samples. The researchers explain that C4 genes have significant variability in their structure, meaning the number of copies and variants of the gene can differ from person to person. This does not normally happen with most other genes, making C4 a gene of interest.
The team was surprised by their results; they found that specific C4 gene structures could predict C4 gene activity in the brain. What is more, they found that certain C4 gene structures in the brain led to increased expression of particular forms of C4 that were associated with increased risk of schizophrenia.
Image credit: Kavan the kid photography
In detail, the researchers found that the more a C4 gene structure led to the expression of the variant C4A in the brain, the greater a person’s risk of schizophrenia.
C4 ‘prunes’ synapses to increase schizophrenia risk Next, the team set out to gain a better understanding of how certain C4 gene structures increase the risk of schizophrenia. The researchers adapted a molecular genetics technique previously used in mouse models to study the “pruning” of synapses - the connections between brain cells, or neurons and the role of C4 in the immune system. Using this adapted method to see what role C4 plays in the brains of mice, the researchers found that the gene is key for synaptic pruning the process by which synapses are streamlined, which normally occurs in late adolescence/early adulthood in humans. Specifically, the team found that C4 activity was required in order for a protein called C3 to be transferred onto synapses, which acts as a signal that the synapses should be pruned. Additionally, the researchers found that the greater the C4 activity in the brains of the mice, the more synaptic pruning they experienced during maturation. The team says their findings may explain why schizophrenia tends to develop in late adolescence or early adulthood; excessive synaptic pruning caused by increased C4 activity at this point in time may trigger symptom onset. The results may also explain why some people with schizophrenia have a thinner cerebral cortex with fewer synapses. The cerebral cortex is the outer layer of the brain that plays a role in memory, language, intelligence and consciousness. What is more, the researchers say their findings support the theory that components of the immune system play a developmental role in the brain, rather than just aiding the fight against infection. “The same proteins are doing one thing in the periphery for immunity, and another thing in the brain,” says McCarroll. “It’s a clever way nature reuses the same molecules for different jobs.”
of the complement system in brain development and in disease, and we could not have made that leap without the genetics,” says study coauthor Beth Stevens, of the Department of Neurology at Boston Children’s Hospital. “We’re far from having a treatment based on this,” she adds, “but it’s exciting to think that one day we might be able to turn down the pruning process in some individuals and decrease their risk.” Commenting on the results, Bruce Cuthbert, acting director of the National Institute of Mental Health - which helped fund the study - says: “This study marks a crucial turning point in the fight against mental illness. Because the molecular origins of psychiatric diseases are little-understood, efforts by pharmaceutical companies to pursue new therapeutics are few and far between.This study changes the game. Thanks to this genetic breakthrough we can finally see the potential for clinical tests, early detection, new treatments and even prevention.” Next, the team hopes to create mouse models with the human C4 variants associated with schizophrenia risk. They aim to find out more about how C4 contributes to synaptic pruning, and to determine whether such pruning may play a role in other neurological conditions. “In this area of science, our dream has been to find disease mechanisms that lead to new kinds of treatments,” says McCarroll. “These results show that it is possible to go from genetic data to a new way of thinking about how a disease develops - something that has been greatly needed.”
“Much research into bipolar has focussed on bio-genetics, but following previous work on schizophrenia, we felt that a similar effect could be found in bipolar. The link between experiencing a troubled childhood and subsequently being diagnosed with this serious condition is extremely strong.”
The authors defined childhood adversity as experiencing neglect, abuse, bullying or the loss of a parent before the age of 19. There was a particularly strong link between emotional abuse with this four times more likely to have happened to people with bipolar. However, the loss of a parent did not raise the risk significantly. The ‘meta-analysis’ approach has been applied in this study for the first time in relation to bipolar disorder and childhood adversity and, as a result, the findings represent a much larger pool of data than has been previously available. The findings have implications for those providing treatment, as they can factor in these childhood experiences when developing personalised therapy plans. Dr Jasper Palmier-Claus, the lead author, added: “Handled sensitively, enquiries about a person’s childhood experiences can make a significant difference to how treatment proceeds and the types of support that can be put into place.” The paper, ‘The relationship between childhood adversity and bipolar disorder: A systematic review and meta-analysis’, was published in the British Journal of Psychiatry.
High blood pressure medications, associated with depression and bipolar disorder About one in three Americans have high blood pressure, and a new study suggests that those on medications to treat this disorder may be at increased risk for depression and a number of other mental health problems. Dana Dovey
A ‘crucial turning point in the fight against mental illness’ While the research is in its early days, the findings undoubtedly represent a breakthrough in the understanding of schizophrenia development. Talking to The Washington Post, Steven Hyman, director of the Stanley Center, hailed the research as “the most significant mechanistic study about schizophrenia ever.” “I’m a crusty, old, curmudgeonly skeptic,” he added. “But I’m almost giddy about these findings.” And it is no wonder scientists are so excited; discovering that the C4 gene may play a key role in a person’s risk of schizophrenia may open the door to strategies that prevent the illness. “This discovery enriches our understanding
A University of Manchester study which looked at more than thirty years of research into bipolar, found that people with the disorder are 2.63 times more likely to have suffered emotional, physical or sexual abuse as children than the general population. In the study, published in the British Journal of Psychiatry, the researchers identified 19 studies from hundreds published between 1980 and 2014 which gathered data from millions of patient records, interviews and assessments. By applying rigorous statistical analysis to the data, the researchers compared the likelihood of people with and without bipolar disorder having adverse childhood experiences, such as physical, emotional and sexual abuse. The findings revealed a strong link between these events and subsequent diagnosis. Bipolar disorder is characterised by extreme depressive and manic states which impair quality of life and increase suicide risk. An urgent need in this field is better understanding of risk factors that can be used to improve detection and treatment. Dr Filippo Varese, one of the study authors, said:
This graph shows the C4 gene on chromosome 6 towering above all other genes that have been linked to schizophrenia, indicating that C4 poses the strongest risk for the disorder. Image credit: Psychiatric Genomics Consortium
Although the exact reason for these results is not clear, the findings could suggest news ways to prevent mental health conditions, and also treat them.The study found that common prescription medications used to treat high blood pressure, such as beta blockers, calcium channel blockers, and angiotensin antagonists, were associated with hospital visits for a number of mental health conditions including depression and bipolar disorder. People taking a beta blocker or calcium channel blocker were twice as likely to have been hospitalized with a mood disorder as those taking an angiotensin antagonist, The Washington Post reported. On the other hand, patients taking an angiotensin antagonist were 53 percent less likely to have been hospitalized with a mood disorder than were those who took no blood
pressure medication. Lastly, thiazide diuretics were not associated with any risk for mood-disorder hospitalization. These findings are based on the medical records of 144,066 adults with an average age of 56. Of this group, 32,130 people were taking one of these four high blood pressure drugs. The individuals were followed over a five-year span, and of this original group, 299 individuals were admitted to the hospital for a mood disorder condition. “There is a lot of data that depression and cardiovascular disease are related ... but current hypertensive practices do not consider depression,” lead study author Dr. Sandosh Padmanabhan told CNN. “This validated those (earlier) findings, but also means blood pressure tablets could be repurposed for mental health conditions.” The study
was merely observational, meaning the researchers aren’t sure of what’s occuring at a molecular levels to cause these results. Still, the findings could have important implications, particularly when it comes to prevention methods and even exploring new avenues of treatment for depression. “There could be some people who are predisposed to depression who we should not be giving these drugs,” Padmanabham told CNN, adding “if angiotensin blockers are protective, then there is a role to repurpose them.”
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The research at Oxford University, published in the British Journal of Psychiatry, was funded by the Medical Research Council. Members of one group of patients were told to use their normal defensive behaviour, such as avoiding eye contact. The rest of the patients were encouraged to lower their defences and try to learn they were safe by approaching computer characters (avatars) and standing toe-to-toe or staring at them.
‘Paranoia melts away’ This group, who fully tested out their fears, showed the biggest reduction in their paranoid delusions. More than half of them no longer had severe paranoia at the end of the testing day. The first group, who used their defences, also saw some reduction in the level of severe paranoia. The study was led by Prof Daniel Freeman, a clinical psychologist at Oxford University’s Department of Psychiatry. He told me: “At the heart of paranoia is the unfounded belief that people are under threat. “With virtual reality we can help the person to re-learn that they are safe, and when they do that, the paranoia melts away.”
Paranoia ‘reduced with virtual reality’ Patients who suffered persecutory delusions were encouraged to step into a computer-generated Underground train carriage and a lift. The simulations allowed the study’s 30 patients to learn social situations they feared were actually safe Fergus Walsh
The Oxford team estimate that around 1-2% of the population have severe paranoia at some point in their lives, typically associated with a mental health disorder such as schizophrenia. Patients have such a strong sense of mistrust that they avoid contact with people and may rarely leave home. The study was small and the patients had just one half-hour session of virtual reality with no long-term follow-up. However, Prof Freeman said the results were “exceptionally good”. He added: “I think this a glimpse into the future of mental healthcare. There is a revolution underway in virtual reality with many headsets becoming available. “As these become more affordable we will see them used not just in clinical settings, but in people’s homes.” Toby Brabham, aged 45, was diagnosed with schizophrenia more than 20 years ago, and has experienced severe paranoia. He told me: “I used to experience persecutory voices - they would be having a go at me. I would avoid going out and when I did it was with my head down so I avoided eye contact. It was very isolating.” Toby is now being successfully treated, and agreed to test out the virtual reality system for the BBC.
‘Exciting to see’ Afterwards he said: “If I go on a Tube train or lift now I will certainly remember the virtual reality experience and I think it will be helpful in reducing any feelings of anxiety that I may have.” Dr Kathryn Adcock, head of neurosciences and mental health at the Medical Research Council, said: “Virtual reality is proving extremely effective in the assessment and treatment of mental health problems. “This study shows the potential of its application to a major psychiatric problem.” Brian Dow, at the charity Rethink Mental Illness, said: “It’s exciting to see cutting-edge technology used innovatively to treat what can be an extremely frightening and disruptive symptom for some people experiencing mental illness.”
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7 A L ZH E I M E R’ S D I S E A S E
Alzheimer’s treatment within reach after successful drug trial
New drug could slow or halt Alzheimer’s, says leader of clinical trials
Tablet that ‘switches off’ production of toxic amyloid proteins could be first treatment licensed in a decade if it is also shown to slow mental decline
“The worst thing about dementia is that you progressively lose the person that you love,” says Anne Tudor, and she knows it first hand.
Hannah Devlin
New drug An Alzheimer’s drug has been shown to successfully target the most visible sign of the disease in the brain, raising hopes that an effective treatment could be finally within reach. A small trial of the drug was primarily aimed at assessing safety, but the findings suggest it effectively “switched off ” the production of toxic amyloid proteins that lead to the sticky plaques seen in the brains of Alzheimer’s patients. If the tablet, produced by pharmaceutical giant Merck, is also shown to slow the pace of mental decline – a crucial question that a major clinical trial should answer when it reports next year – it could be the first treatment for Alzheimer’s to be licensed in more than a decade. Prof John Hardy, a neuroscientist at UCL who first proposed that amyloid proteins play a central role in Alzheimer’s disease, welcomed the results. “People are excited,” he said. “This is a very nice drug and I’m sure Merck are feeling very pleased with themselves.” Matt Kennedy, who led the trial at Merck, said: “Today there are very limited therapeutic options available for people with Alzheimer’s disease, and those that exist provide only short-term improvement to the cognitive and functional symptoms. They do not directly target the underlying disease processes. There is an urgent need for [these].” The new therapy is designed to do this by halting the steady production of amyloid-beta proteins, which are known to clump together in sticky plaques in the brains of Alzheimer’s patients. A leading theory of Alzheimer’s is that the accumulating proteins kill off healthy neurons, eventually leading to memory loss, cognitive decline and changes to personality. Kennedy said it was too early to predict when a drug might reach the market if the next step is successful. “We are eagerly awaiting the results of the phase three clinical trials,” he said. “It is premature to speculate on availability.” In the trial, published in the journal Science Translational Medicine on Wednesday, 32 patients with early stage Alzheimer’s disease were given the drug, called verubecestat, daily for seven days. Healthy volunteers were also given the drug for up to two weeks. This was not long enough to show visible changes to the accumulation of plaques in the brain, by MRI scans for instance. However, samples taken from the fluid surrounding the brain showed the drug had reduced the levels of two compounds that are known to be the building blocks for abnormal amyloid proteins. Hardy said
that the changes to the biomarkers convince him that the drug is successfully targeting the buildup of plaques in the brain. The real remaining uncertainty, he said, was whether this would convert into cognitive benefits for patients. “What we have to be worried about is that the plaques have set off other pathologies - that it is too late,” he said. The drug works by blocking a brain enzyme called BACE1, which fuels the production of two small molecules that link together to form amyloids. Mutations in genes related to BACE1 have been found in people who appear to be protected against Alzheimer’s disease.
Attempts There have been previous attempts to develop drugs that inhibit BACE1, but these have mostly failed due to unacceptable side-effects, such as liver toxicity and eye problems. The Merck drug appears to have very few side-effects and it will be the first of its kind to make it into a large efficacy trial. The company is running two phase three trials, in 1,500 patients with mild to moderate Alzheimer’s and in another 2,000 patients in the earliest stage of the disease. The results of the first of these are due to be reported in July 2017. There are 850,000 people with dementia in Britain, and this figure is expected to reach one million by 2025. Alzheimer’s is the most common form of the condition. Rosa Sancho, head of research at Alzheimer’s Research UK, welcomed the findings, adding that the Merck drug is one of several that are heading into the final stages of clinical testing. “There is a wave of potential new treatments currently being tested for dementia, with the results of these studies hotly anticipated over the course of the coming months and years,” she said. Competing drugs include one developed by the biotech firm Biogen, which reported promising results in August and which also targets the plaques. The Biogen drug aims to sweep the proteins away once they appear rather than halting the production of proteins in the first place, however. “With us, it’s a question of switching off the tap. With them it’s mopping up the water,” said Ian McConnell, a spokesman for Merck. Hardy suggested that Merck’s drug is likely to be far cheaper and easier to produce than the Biogen therapy, which involves injecting patients with antibodies.
How BACE1 blocking drug could reduce toxic proteins in Alzheimer’s patients
Scientists think they have a good drug target to prevent Alzheimer’s
Carolyn Webb
Patients who suffered persecutory delusions were encouraged to step into a computer-generated Underground train carriage and a lift. The simulations allowed the study’s 30 patients to learn social situations they feared were actually safe. Tibi Puiu
Alzheimer? Alzheimer’s disease is one of the most common neurodegenerative disorders, affecting 5.4 million Americans. It’s estimated that one in three seniors die of Alzheimer’s or some other form of dementia, and life’s not easy once the disease takes its toll either. To make matters worse, there’s no cure — only treatments that help stave off the inevitable. That’s why a team from Baylor College of Medicine, Texas Children’s Hospital and Johns Hopkins University School of Medicine, were more preoccupied with subduing early events that lead to Alzheimer’s. What causes Parkinson’s, Alzheimer’s and dementia is the accumulation of certain proteins in the brain, specifically the ‘tau’ protein. When there’s too many of these proteins in the brain, they become toxic and cause neural degeneration. It’s sort of like the plaque which causes tooth decay, which is why scientists refer to this protein build-up as ‘neural plaque’.
Scientific Research “Scientists in the field have been focusing mostly on the final stages of Alzheimer’s disease,” said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow at the Baylor College of Medicine. “Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later.” Neurons, like any cell, control the amount of protein they make through enzymes. There are, however, literally thousands of enzymes that might be involved with tau accumulation. If you thought what came next was some sly move to help sort through all of these possibilities, I’m sorry to break it to you: there wasn’t. The team went at it the old fashion way, inhibiting enzymes called kinases one by one. “We inhibited about 600 kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau,” said Dr. Huda Zoghbi, professor of molecular and human genetics at Baylor. The researchers screened the enzymes by studying them in human cells cultured in a dish, but also in genetically modified fruit flies. Due to their short breeding cycle, the fruit flies proved ideal as it would have otherwise taken countless years to screen as many enzymes in a rodent model, for instance. Human cultured cells,
while useful, “cannot model complex nervous system functions,” said Dr. Juan Botas, professor of molecular and human genetics at Baylor.Next, they put their results to the test by trying to replicate them in a mouse model — and they were successful, as reported in the journal Neuron. “We found one enzyme, Nuak1, whose inhibition consistently resulted in lower levels of tau in both human cells and fruit flies.Then we took this result to a mouse model of Alzheimer’s disease and hoped that the results would hold, and they did. Inhibiting Nuak1 improved the behavior of the mice and prevented brain degeneration.” said Zoghbi. “Confirming in three independent systems – human cells, the fruit fly and the mouse – that Nuak1 inhibition results in reduced levels of tau and prevents brain abnormalities induced by tau accumulation, has convinced us that Nuak1 is a reliable potential target for drugs to prevent diseases such as Alzheimer’s,” said Zoghbi. “The next step is to develop drugs that will inhibit Nuak1 in hope that one day would be able to lower tau levels with low toxicity in individuals at risk for dementia due to tau accumulation.” Armed with this biological mechanism at hand, it’s possible to design drugs that target it and keep dementia at bay. Maybe, not all that different from drugs that lower cholesterol, thus preventing atherosclerosis and heart disease. “When people started taking drugs that lower cholesterol, they lived longer and healthier lives rather than dying earlier of heart disease,” said Zoghbi. “Nobody has thought about Alzheimer’s disease in that light. Tau in Alzheimer’s can be compared to cholesterol in heart disease. Tau is a protein that when it accumulates as the person ages, increases the vulnerability of the brain to developing Alzheimer’s. So maybe if we can find drugs that can keep tau at levels that are not toxic for the brain, then we would be able to prevent or delay the development of Alzheimer’s and other diseases caused in part by toxic tau accumulation.”
Her partner, Edie Mayhew, 65, was diagnosed six years ago with early onset Alzheimer’s disease. The Ballarat couple try to stay positive, and travel interstate and overseas giving talks on healthy living. But Ms Tudor has watched as Ms Mayhew, a former driving instructor, has lost the ability to cook a meal, choose clothes and remember conversations. They welcomed the news that human trials will begin in Melbourne on Monday for a new drug that has been shown to halt the progression of Alzheimer’s disease in mice and to reverse memory loss. Volunteers who have been diagnosed with mild to moderate Alzheimer’s are being sought to take an oral medication and be monitored on its effects. The study’s lead researcher, Austin Health associate professor Michael Woodward, said the drug, called CT1812, had been found in mice to negate the effects of the toxic protein amyloid beta – which causes Alzheimer’s – at both cellular and behavioural level, and to improve memory. He said the new drug could slow or halt the which 350,000 Australians currently suffer,
with one million projected to be diagnosed by 2050. Susan Catalano, chief science officer of the trial’s backers, private US biotech company Cognition Therapeutics, or CogRx, said previous therapies had focused on trying to eliminate plaques caused by the build-up of amyloid beta in the brain. The new approach focused on how these proteins link together to form clumps called oligomers, which bind to receptors in the synapses responsible for communication between brain cells. The binding process kills off parts of the receptors and, in turn, disables the synapses. The process of memory formation fails, and Alzheimer’s symptoms start to appear. Dr Catalano said the drug CT1812 had been found – in mice that had been genetically engineered to over-produce amyloid beta – to shield synapses from the effects of oligomers It did this by the drug itself binding to one type of receptor, changing the receptor’s shape so the oligomers are either unable to take
hold, or are displaced. A selection of CogRx study drugs, including CT1812, reversed the memory loss after one month of treatment and sustained the memory improvement for six months. Volunteers aged 50 to 80 are needed for the trial at Austin Health, in Heidelberg, Melbourne Health at Parkville, Epworth Hospital in Richmond and with Dr Philip Morris in Southport, Queensland from now until January. Associate Professor Woodward said previous studies had tried to neutralise amyloid beta, but this therapy was about protecting cells from its effects – “a very new and refreshing approach”. Ms Mayhew welcomed the trial and said she would consider signing up. “If it can help other people with dementia, then I’m happy to do it. It might help me as well,” she said. Ms Tudor said: “It sounds really promising. We’d love to see something to stop it from getting worse – or even better, to prevent it from happening in the first place.”
8 PAR K I N S O N ’ S D IS E AS E
Canton’s Rock Steady Boxing hits back at Parkinson’s disease Program uses boxing and other programs to help people battle progressive nature of the neurological disease. Josh Weir
“Parkinson’s is like a dog chasing you,” said Gooding, a 69-year-old Hartville resident who has been diagnosed for eight years. “If you slow down, he’s going to catch you. So you’ve got to keep going.” And through the Rock Steady program, people aren’t just running from it. They’re fighting back. Influenced heavily by boxing training methods, Rock Steady offers people a chance to battle the progressive nature of the neurological disease. Canton’s Dick Nicely heard of the program, which was founded in Indianapolis in 2006, earlier this year. He was fascinated about the boxing element. So the 70-year-old Nicely, who has been diagnosed with Parkinson’s for 17 years, brought it to Stark County. He set up shop at 1240 Dueber Ave. SW in Canton, a location that connects to the construction business he owns, R.G. Smith Company. “I exercise and I think that’s key to my health,” he said. “Once I found out about this, it was just an extension to what I do anyway. So it was a natural evolution of exercise.” Nicely laughed. “I didn’t even know what a speed bag was before this.” Now he has one at his house.There is no hand-to-hand combat in Rock Steady. There is no ring. But participants hit speed bags, heavy bags and double-end bags. They also hit punching mitts worn by an instructor. “Punch like you mean it!” instructor Michelle Wintrow implored a recent class as high-energy music pumped through the facility. Participants shuttle from station to station during the hourlong class, which includes weights, battle ropes, tire
flips, BOSU balls, stretch bands and TRX Strength Bands among other forms of exercise. Tremors in the hands and fingers are Parkinson’s most common symptoms. But the disease also affects movement, flexibility and speech. Rock Steady aims to combat those effects with exercise centered on hand-eye coordination, speed, balance, core strength and agility. They even encourage participants to express themselves vocally, and to do it loudly. “Rock Steady!” the group shouts as they begin the class, like a sports team breaking a huddle. “I’m stronger and I’ve got better balance than I did before,” said 79-year-old Reno Mason of Canton, “and it’s only been two and half months that I’ve been in this program.” As Wintrow says, Rock Steady intends to “take people out of their comfort zones.” It is supposed to be a challenge. That being said, Rock Steady is tailored to each person’s capabilities.Gary Wise, who is wheelchair-bound most of the time, goes at his own pace through the activities. He stands when he can, and that is happening more often as he attends more classes. Meanwhile, David Nelson of Jackson Township moves as well as any 61-year old you will find and tackles each activity with ferocity. “It’s a big part, being yourself and letting it all hang out,” said Nelson, who has battled Parkinson’s for 20 years. “Everyone has different capabilities. You’re accepted. They meet you where you are.” After watching Nelson whale away at the punching mitts, one male observer mentioned, “I think he would kick my butt.” “It’s fantastic,” Nelson said about Rock Steady.
“It’s a hard workout and it’s high energy. It reinforces things like flexibility, balance and strength in a fun way. And you get your frustrations out, too.” Thirteen people participated in this particular class. That included Claudia Goerke of North Canton. The 63-year-old former nurse has suffered from multiple sclerosis, a disease that affects the brain and spinal cord, for 37 years. She believes there are some crossover benefits with Rock Steady. “You’ve got to stay active,” she said. “You can’t sit around.” Nicely was so happy with the early results of the class that he had a back wall knocked out to add 1,000 square feet of space, bringing the facility to about 2,500 total. The bright room includes attractive track lighting, a big “Rock Steady Boxing Canton” banner on the wall and MMA-style floor padding in case anyone takes a fall. Classes are held Mondays and Wednesdays from 1:30-2:30 p.m. and Saturdays from 10:30-11:30 a.m. Cost is $100 a month. That includes the ability to bring a “corner man” — usually a spouse or friend who can aid the participant and offer encouragement. For more information, call 330-323-6630 or visit www. facebook.com/rocksteadyboxingcanton. Parkinson’s mainly affects older men, with genetics playing a big part. There is no cure for the disease. It is a life changer. Gooding had to retire from being a CPA. Nelson had to retire from being an ophthalmologist. But Parkinson’s doesn’t have to be a life-ender. And that’s the point of Rock Steady. “I’d rather not have been forced into retirement,” Gooding said. “I’d rather not have to come here three days a week. But I want to live, too, and I want to live a quality life.”
ISU research may suggest new cure for Parkinson’s disease Recently published research from Iowa State University may hint at a new treatment for Parkinson’s disease. Iowa State University
In a paper published in the academic journal Nature Communications, ISU scientists identified a protein called Prokineticin-2 (PK2) that may protect brain cells and is expressed with greater frequency in the early stages of Parkinson’s disease. “The neurons use PK2 to cope with stress. It’s an in-built protective mechanism,” said Anumantha Kanthasamy, a Clarence Hartley Covault Distinguished Professor in veterinary medicine, the Eugene and Linda Lloyd Endowed Chair of Neurotoxicology, and chair of biomedical sciences at Iowa State. Kanthasamy, one of the paper’s lead authors, has been working to understand the complex mechanisms of Parkinson’s and searching for a cure for the past two decades. Prokineticin-2 stimulates the neurons to produce more mitochondria, the part of the cell that produces energy. The resulting improved energy production helps neurons withstand the ravages of the disease, which is a neurological disorder that results in insufficient levels of dopamine in the brain. Parkinson’s disease is a progressive disorder
that takes years to develop. A better understanding of Prokineticin-2 could turn up a means of slowing development of the disease or lead to new therapies, Kanthasamy said. For instance, there may be ways to stimulate more production of the protein or protein analogs to bind with its receptors on neurons, he said. The research team took a multidisciplinary and integrated approach to studying Parkinson’s disease. The study was funded by a grant from the National Institutes of Health to Kanthasamy and Arthi Kanthasamy, a professor of biomedical sciences and Anumantha’s spouse. Six graduate students in Kanthasamy’s lab also contributed to the study, including co-first authors Richard Gordon and Matthew Neal, as well as researchers at other institutions. The scientists studied cultured brain cells, a rodent model and post-mortem human brains to track changes brought on by Parkinson’s disease, and they confirmed a high expression of Prokineticin-2 in each facet of the study.
It was this team effort that resulted in a comprehensive finding, Arthi Kanthasamy noted. The discovery prompted the research team to investigate more thoroughly. “Of the thousands and thousands of factors we tracked in our experiments, why was this protein expressed so highly?” Arthi Kanthasamy said. Finding the answer to that question poses a challenge that will take time to overcome, but the potential appears to be significant, she said.