2016 winter brainwaves newsletter

brainWAVES The Newsletter of the Brain Foundation

Winter 2016

Brain Awareness Week 2016 Dementia Awareness Webinar – did you log in?

The incidence of Dementia is increasing and is prominent in the news cycle. To address community concerns, Brain Foundation held an online presentation – “Dementia: How to Beat the Odds” to provide more medically authoritative information.

As the population ages, dementia is increasing in the older cohorts. But Dementia need not be a normal part of ageing. It is a syndrome caused by a variety of brain illnesses that affect memory, behaviour and ability to perform everyday activities. Despite research so far, very few breakthroughs are happening because the funding is limited.

Dementia will continue to affect many of the population.

Our free online presentation was moderated

by Professor Steve Robinson from RMIT School of Health and Biomedical Sciences and a director of Brain Foundation Victoria.

Questions addressed were: • Why dementia is on the rise?

• How to minimise your risks and implement preventative strategies;

There was also an interactive Q&A session at the end of the presentation.

Offered to our supporters through email, social media and the National Headache Register, hundreds of people attended in what was an extremely informative and entertaining expert presentation.

We have had many positive responses.

Those who attended in took away valuable information.

More for us. Less for them.

To help us give more to research and less to administration costs, Brain Foundation is implementing e-mailed receipts. If you would like your receipt e-mailed, please ensure we have your current details. You can fill out the section on the enclosed letter, make a donation on-line or e-mail us so we can update your information.

Elizabeth wrote: “I am doing a Degree in Dementia at UTAs. I am 77 and enjoying the challenge. Some of my colleagues attended as well. Thank you for a wonderful, interesting lecture. The information was very beneficial.”

Due to the success of this Webinar, we will be holding another one in June on the topic of Dystonia. I’m sure most of our supporters may know a little about Dystonia but in order to learn more, then please log in. See our Dystonia section for the details.

In the meantime, see Healthy Brain for some puzzles to stimulate those brain cells.

• Scientifically proven research on how to prevent dementia; • Does drinking champagne everyday help prevent dementia?

Valé John King It was with sadness that the Brain Foundation learned of the passing of John earlier this year.

John, a former Senior Partner of PricewaterhouseCoopers, presided as the Foundation’s Treasurer for over 10 years and remained very close and

committed to the board and management of the Foundation.

During John’s term, the Foundation grew significantly in size and John helped ensure that we were to remain strong well into the future. John recruited his successor, our current Treasurer, Bill Kuchta who is

also a former Senior Partner of PricewaterhouseCoopers.

Tributes flowed from John’s many friends and these will go towards research into Parkinson’s in John’s name.

Contact the Brain Foundation PO Box 579, Crows Nest NSW 1585 Telephone: 02 9437 5967 or 1300 886 660 Email: info@brainfoundation.org.au Visit our websites brainfoundation.org.au and headacheaustralia.org.au

Dystonia News DYSTONIA: Muscles Behaving Badly Dystonia is the third most common movement disorder worldwide.

The cause, while neurological in origin, is unknown.

SUPPORT GROUP The Australian Dystonia Support Group is growing every day with over 400 members.

If you would like to know more, contact the Australia Dystonia Support Group - details below or contact Lee Pagan at ADSG@live.com.au.

Dystonia Webinar Learn more about Dystonia and its effects Following the success of our recent Webinar on Dementia and how to maintain a Healthy Brain, we will be holding another on the topic of Dystonia. This will take place on June 7.

People who suffer from a condition often learn a lot about it and potential treatment options. But, you never know what more you may learn. Many attendees from our Webinars on Dementia and the recent Migraine World Summit have expressed that they “learned more in a few days than they have in years”.

So, sign up to attend!

Ask family and interested friends to attend as well – it will help with their understanding of your everyday lives.

Great Wall of China: Great fundraising effort.

In October this year, Nicole Botica will be taking on a personal challenge to walk a section of the Great Wall of China to raise funds and awareness of Dystonia.

“My aim is to raise as much money as I can for Brain Foundation and specifically for the neurological condition Dystonia. My amazing family has felt, first hand, the heart breaking effects Dystonia has on people and their lives. So, in Loving Memory of John Aldrick from the extended family, I hope I can do great things for the people who battle this disease every day and for the fabulous researchers at the Brain Foundation.”

This sounds like such an exciting challenge to do to raise awareness of Dystonia we all wish we were going too! If you would like to support Nicole on this fabulous adventure then please visit ‘My China Challenge’ at gofundraise.com.au.

Registration details are on the Brain Foundation website.

Dystonia Awareness Month – this September

Nicole is pictured with niece Molly who survived a brain tumour in 2010.

If you think this sounds like a great way to raise some money for a worthwhile cause and would like to do a challenge such as this yourself, then have a look at Huma Charity Challenges, www.humacharitychallenge.com. They have a great selection of ‘challenges’ at various times of the year, so might be just what you are looking for. Just remember, you heard it here first!

Dystonia is a Neurological Movement Condition which

Australian Support affects adults and Dystonia children. It can affect any part ofGroup the body and causes muscles to contract or spasm. This may Contact Details cause pain, tremors, twisting and other uncontrollable ADSG Website: australiandystoniasupportgroup.wordpress.com/ movements. Currently there is no cure

ADSG Community Page: facebook.com/AustralianDystoniaSupportGroup

Please help those affected by joining in and spreading awareness of this condition

ADSG Closed Support Group on Facebook: facebook.com/groups AustralianDystoniaSupportGroup/

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The Newsletter of the Brain Foundation Make it you mission to

spread the word!

Headache Australia Migraine World Summit

As reported in the last Brainwaves newsletter, updated information on worldwide disability rated Migraines as the 6th highest cause of disability worldwide in terms of years lost to disability.

A severe migraine can be as disabling as quadriplegia or active psychosis.

Migraines are more common than diabetes, epilepsy and asthma combined. There are around 71,000 migraine attacks every day in Australia with around 3 million Australians affected.

Yet, despite the prevalence of migraine, it remains under

diagnosed and under treated with less than 50% of patients consulting a doctor. And, for those who do, finding the right doctor can be difficult. Studies have shown only 4 hours are committed to headache disorders in undergraduate medical training worldwide.

In April this year, Headache Australia took part in the first Migraine World Summit, a free online event where migraine patients had the opportunity to get access to the world’s top migraine experts.

Over 30 doctors, professors and specialists gathered from world leading institutions, clinics, universities and hospitals – including Australia – to help answer some of the most difficult questions for patients in desperate need of relief. As

sufferers would know, there can be a significant wait to get good advice via a specialist. The Migraine World Summit provided unprecedented access to dozens of experts for those suffering from this debilitating disorder. It was a great opportunity to jump the queue and hear straight from the doctor about the latest best practices and approaches being used by leading physicians.

Australia to help fund headache research.

If you were not available to access the free talks in April, don’t worry. You can get access to 3 free talks from the Summit via migraineworldsummit.com or you can order all the talks from the Summit at headacheaustralia.org.au/ summit and 50% or your order will be donated to Headache Australia. Over $1600 has already been raised for Headache

“I thought I knew a LOT and I still learned a lot. So this was great.”

Anny F

Below are a few comments from people who attended the Summit: “Thirty two years of migraine and I learned more in 5 days than I have in all those years with experts of my own. I am so glad I got the message to attend” Sharon N

“This is absolutely a.m.a.z.i.n.g!

Thank you so much for putting this together. I have learned something from every talk I’ve listened to so far…those I thought would probably not be relevant were actually much more relevant than I could have imagined.”

Helen P

Headache Awareness Week

Cefaly

– 12 to 16 September 2016

Headache Australia continues to offer Cefaly Devices to our Register members at a special rate.

In 2015 Headache Australia ran a series of face to face lectures about headache and migraine in the eastern states. The talks were given by prominent neurologists and proved to be extremely popular with our Register members who could attend.

So, in 2016, we will be running another series of these talks in each state. Look out for the email advice with further information.

The dates for these talks are as follows: Monday, September 12: Brisbane with Dr Nicole Limberg Perth with Dr John Cunningham Tuesday, September 13: Sydney with Dr Karl Ng Wednesday, September 14: Melbourne with Dr David Williams Thursday, September 15: Adelaide, Dr TBA

Cefaly is a TENS machine which works particularly well on headaches toward the front of the head.

Latest data from Cefaly suppliers show that a significant reduction in headache and migraine is experienced by up to 75% of users.

It is a drug free alternative and can also work well in conjunction with a reduced usage of your existing drugs. Give it a go! Ring our office to go on a waitlist for a loan Cefaly…but be aware it could be a long wait!

Headache Australia is a division of Brain Foundation Members on our database receive Brainwaves newsletter twice a year. All donations made by Register members go directly to Headache Research projects.

Are you a Headache Register Member?

Our Register Members receive regular email updates of current information as we receive it. We send information about new research trials that you can choose to be involved with.

All donations made by Register Members go only to Headache research.

Your email address is required. Register at headacheaustralia.org.au Disclaimer: Headache Australia is not a medical office and cannot offer medical advice. We stress the importance of discussing any issues you have with your medical practitioner.

Winter 2016

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Fabulous Fundraisers Callum paddles up a storm In January this year, Callum Smith paddled his way from Sorrento SLSC to Port Melbourne on a heavy Surf Lifesaving Board. Why do this some of you may ask?

Thanks to Chris Hartmann and her family for their stunning Christmas light display. The many visitors who came along to share the spirit were asked to donate to Brain Foundation for research into Aneurysms. The town has lost two members from the same family to this condition recently and so it was a cause close to many hearts.

He was raising funds for Brain Tumour research after his sister Jacinta suffered from a tumour in her brain stem. Successfully treated, Callum, a keen surf life saver, wanted to increase knowledge in the community and funds for research.

As we had advertised this inspirational endeavour in previous newsletters, many of our donors supported Callum towards a very generous total. He also picked up donations on the overnight stops at Surf Clubs up the Bay and achieved his goal to increase awareness of this terrible condition.

Goondiwindi lights up the Christmas sky

Thank you to everyone from Goondiwindi who supported Chris and for your generous donations to this worthy cause.

Brain Foundation Victoria President, Prof. Robert Medcalf (right) was there at the start and the ‘finish line’ and is pictured with Callum (left) and his family.

Abbey Dynasty gallops to a fine finish Brain Foundation sends a very sincere thank you to the organising committee and all the participants in the Abbey Dynasty Campdraft Carnival who travelled long distances to make this event such an outstanding success.

The Campdrafting Carnival, held in September last year, was a memorial to the great horseman, Theo Hill, his mate Harry Ball and the champion Australian Stock Fiona with Coral Ball and the Brain Foundation ‘cheque’ at the Abbey Memorial, Willawarrin Horse, Abbey. Each of the 700 entrants on Showground. the weekend was descended from Abbey.

Local farmers and owner drivers made the event possible by providing and transporting 2,000 head of cattle.

In 1955, Abbey was born in the small NSW North Coast town of Willawarrin. In February this year Fiona from the Brain Foundation travelled back to Willawarrin where Abbey’s owner, Mrs Coral Ball, presented a cheque for research into Dementia. The Garvin Institute and Can Assist Narrabri were also recipients of donations from this very successful weekend.

2016 Tamworth Fair…

Gerald is pictured with Braiden’s family, friends and players.

Wanting to raise awareness and research funds in Braiden’s name, the Foord family and friends came together and dedicated their annual Football Charity weekend to his memory.

Brain Foundation was the recipient for our research programme.

A great weekend was had by the more than 1500 players. A big thank you to the organisers and all of Braiden’s family and friends for such a successful weekend and wonderful contribution.

The Newsletter of the Brain Foundation

A heartfelt thank you to Coriana Boothey, who organised a very successful trivia quiz night – the “Nutty Quiz Night”, earlier this year. Held in honour of her very dear friend and work colleague, Deborah Nuttall, the night raised significant funds to go to Aneurysm research.

Thank you both so much for your support at a time of great loss.

Football is certainly a popular sport and in March this year, this popularity was put to very good use.

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Everyday Hero, Heroes

And a very special thank you to Erica Williams, who is running in the Brisbane City 2 South Running Festival in June. The loss of a loved one to a Brain Tumour has inspired this magnificent effort from Erica and her supporters. Best of luck on the day!

Everybody loves a good game of Football!

Early in 2016, the Foord family lost a son and brother, Braiden, to an Aneurysm. As is usually the way with Aneurysms, it was sudden and unexpected.

Chris Hartmann's Christmas Light Display

is on again at the Tamworth Racecource, Sunday November 20.

Come along and grab some fabulous Christmas presents from the many high quality items that will be available.

We send our sincere thanks to the Committee who work so hard every year to generously support our research programme.

Sir Charles Bright Scholarship Trust 2016.

Congratulations Natalie Natalie Palinkas is the proud recipient of this year’s Brain Foundation Scholarship.

Suffering from PTSD after witnessing a horrific vehicle accident where she rendered assistance to a gentleman with life threatening injuries, Natalie is continuing her Cert IV in Community Services and hopes to work in a Community Service Organisation assisting people with special needs.

The Sir Charles Bright Scholarship was established in 1985 to honour the former judge of the Supreme Court who did much for the disabled and disadvantaged in the community.

The Scholarships are awarded to disadvantaged persons suffering from illness or injury allowing them to continue their secondary education.

South Australia’s Higher Education and Skills Minister, Dr Susan Close with Gerald Edmunds and award winner Natalie Palinkas.

Exercise your brain Healthy Brain The more you work your brain, the more it works for you! Look after your most important asset!

Mazes are a great way to help you work your brain. They help you at concentration, forward thinking, attention to detail and they are also a great lesson in patience. Some mazes, like life, can have more than one journey. How many mazes can you find in this maze?

ABC Active Memory – now free on line Will you take the challenge?

A couple of years ago we advised our supporters of this great web site with online Brain Training puzzles and games.

As you get better, the puzzles get more difficult to do. Well, from the end of May this web site free to use.

So look it up and have a go. Your partner may not thank us for this! Activememory.com

Winter 2016

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2016 Progress Reports A diagnostic profile of Vestibular Migraine using semicircular canal and otolith fundtion tests 2013 Brain Foundation Grant

Chief Investigator: Dr Sally Rosengren Vestibular migraine (VM) is a manifestation of migraine in which patients experience recurrent episodes of vertigo, which may coincide with a migraine headache, aura, phonophobia or photophobia (Lempert et al., 2012). Vertigo is a false sensation of movement of the self or surrounds and is a common and disabling symptom afflicting at least one million Australians each year.

Vestibular migraine is the second most common cause of recurrent vertigo, but is often left undiagnosed and untreated due to the lack of clear diagnostic criteria and clinically applicable laboratory tests.

Our project therefore aimed to improve the diagnosis of patients with vestibular migraine.

Unlike other episodic vestibular disorders, the duration and quality of vertigo in VM is so diverse that it can mimic many other common vestibular disorders. Very short episodes lasting seconds to minutes can be difficult to distinguish from benign positioning vertigo (BPV), intermediate episodes lasting several hours are similar to Meniere’s Disease (MD) and long episodes lasting more than a day can be confused with vestibular neuritis (VN). We therefore aimed to investigate the diagnosis of VM by comparing it to the conditions it mimics, based on the duration of episodes.

Preliminary results We planned to recruit 100 consecutive patients with definite or probable VM from the neuro-otology clinic of the Institute of Clinical Neurosciences at Royal Prince Alfred Hospital. Funding from the Brain Foundation of Australia has enabled us to recruit and collect data from 129 patients in total. Patients with clinically probable or definite migraine were recruited. Of the patients whose data has thus far been classified and analysed, 11 had probable or definite VM with short vertigo attacks (4 M, 7 F, aged 37-62 years) and 20 patients had intermediate duration attacks (6 M, 14 F, 15-68 years). We have not yet recruited patients with long duration attacks. In terms of patients with conditions mimicked by VM, we

have recruited and test 21 patients with definite MD (7 M, 14 F, 27-85 years) and are currently recruiting patients with BPV. Clinical characteristics of patients in these groups are shown in Tables 1 and 2.

Table 1. Clinical Features (%) Sponta- Posineous tional vertigo vertigo

Spinning vertigo

Migraine vertigo

VM short

55

64

55

100

VM intermediate

90

35

25

100

MD

100

37

84

37

Table 2. Symptoms during vertigo attack (%) Headache

Tinnitus

Hearing loss

Fullness

VM short

18

36

0

64

VM intermediate

65

15

20

40

MD

26

89

100*

89

*HL was either worse during the attack or was reduced but no longer fluctuated Intermediate-duration episodes of VM versus MD Patients with VM with attacks lasting minutes to hours can be difficult to distinguish from those suffering from MD. While more than half of the VM group analysed so far describe having migraine at the time of vertigo (65%), a significant proportion do not, leading to a diagnosis of probable VM instead of VM. Patients with MD are less likely to describe headache as a feature of their episodes, though this does occur 26% of the time.

Patients with MD report more aural symptoms, including fluctuating tinnitus and hearing loss, as expected due to the diagnostic criteria for MD. However, while the presence of tinnitus and hearing loss seem to be relatively good discriminators between the diseases, a feeling of fullness of the ear is less discriminative, as 40% of migraine sufferers also describe a sense of fullness. The other major difference is that MD patients mostly describe their vertigo as true spinning vertigo (84%),

while patients with VM are more likely to complain of rocking, tilting, or other manifestations of vertigo. In contrast to previous reports, both groups of patients with VM (short and intermediate duration) are only slightly more likely to report being sensitive to self-motion (55% and 60%) or visual motion (45% and 55%) compared to patients with MD (47% and 42%).

The pilot data has shown higher rates of otolith abnormality in the patients with MD than VM (i.e. cVEMP and oVEMP asymmetry ratios). cVEMPs were abnormal in 40% of MD patients compared to 20% of VM patients, and oVEMPs were abnormal in 20% of MD patients and only 5% of VM patients.

This is consistent with preliminary data collected by the Dr Welgampola, suggesting that VEMPs are robust in patients with VM (Taylor et al., 2012). oVEMPs were significantly smaller in affected vs unaffected MD ears (P<0.05), even after exclusion of frankly abnormal responses, suggesting the presence of subclinical damage to the otoliths.

Semicircular canal function (i.e. the gain of the vHIT in each canal plane) fell in the normal range for all patients with VM, while 17/20 patients with MD had normal results.

Two patients had canal paresis of all three canals in the affected ear, while another had reduced function of the right posterior canal on the affected side.

Group analysis (excluding the 3 patients with frank abnormalities) additionally showed that the gain for the affected posterior canal was significantly lower (P = 0.002) in the MD patients (0.83) than the VM patients (0.94), suggesting that MD produced subclinical abnormalities that might become significant over time.

Short- versus intermediate-duration episodes of VM There are already interesting differences emerging between the migraine patients who report having short (<5 mins) compared to intermediate length (mins-

hours) vertigo attacks. Patients with very short episodes are less likely to describe their vertigo as occurring spontaneously and more likely to complain of positional vertigo (64% vs 35%). The positional component of vertigo, along with the short duration of attacks, is the feature that most resembles BPV and causes difficulty in diagnosis. In the short episode group, the temporal link between migraine and vertigo is relatively weak (18%), while the patients report surprisingly high rates of tinnitus (36%) and fullness of the ear (64%) during attacks, features more usually associated with MD. Hypothesis vs Findings The proportions of patients with short (up to 5 min) and intermediate (5 min to 24 hours) vertiginous episodes in our sample are likely to ultimately match the rates expected based on previous reports (40% and 30%, respectively), but we have not yet recruited any patients with long duration (greater than 24 hours) episodes (Dieterich and Brandt, 1999; Lempert et al., 2012). This might be due to the fact that patients with long episodes are often initially diagnosed with vestibular neuritis, and only present for follow-up once a new episode occurs, which may be some time after the first attack.

We have encountered higher rates of vestibular abnormality in the patients with MD than VM, as expected based on previous research on otolith reflexes (e.g.

Taylor et al., 2012). However, the findings concerning semicircular canal function, as assessed by head impulse testing in all three canal planes for each ear, are novel.

As expected, there are already differences emerging in the clinical characteristics and test results of patients with different durations of VM and between VM and one of its mimics, MD. However, as the number patients with definitive diagnosis and classification in our study is currently small, it is premature to conduct full regression analysis to determine the clinical and test factors that most discriminate between patients.

See website for complete reports and References 6

The Newsletter of the Brain Foundation

Oncogenic transformation of human neural stem cells into Medulloblastoma-forming cells Chief Investigator: Dr Jacqueline Whitehouse (nee McGlade) Medulloblastoma is the most common making the cells “tumour-prone” via the cells. We are currently in the process of malignant brain tumour in children and use of a short-hairpin RNA to downregulate optimising lentiviral production in order to the most significant cause of childhood the tumour suppressor gene TP53. ensure the best possible transduction rate cancer-related death. If we are to improve of the human neural stem cells.

During the process of preparing these the outcomes of children with these constructs, we discovered that a research Once established, these cell lines will cancers it is imperative that we have a group led by Dr Charles Eberhart at The be implanted into the cerebellum of goodunderstanding of what drives tumour Johns Hopkins Hospital in Baltimore immunodeficient (nude) mice (106 cells growth, which will allow us to design better (Maryland, USA) was working on a similar per mouse) (Figure 1). Ten mice will be treatments. approach to modelling medulloblastoma implanted per cell line. This number We have known for a long time that some in the laboratory and had successfully is based on our laboratory’s previous patients with medulloblastoma respond created a Group 3 (MYC-driven) model of experience with implantation of cells, and well to treatment, but others do not and medulloblastoma. This model was achieved takes into account the risk that some cell are likely to die from their disease. In the using human neural stem cells transformed lines do not have a 100% establishment past we haven’t had enough information using lentivirus coding for a dominant rate (as low as 50% is expected in some to understand why this is, but recent negative R248W p53 (similar in concept to cell lines based on published mouse research has revealed that although our short-hairpin RNA approach), hTERT to modelling data). medulloblastomas may look the same immortalise the cells and c- MYC which is down a microscope, when examined more associated with Group 3 medulloblatoma. Tumour growth in implanted mice will be closely at the genetic level, they are not all Additionally, they also transformed the cells monitored via measurement of luciferase the same and in fact there are at least four with a constitutively active AKT which was activity using an IVIS Spectrum imager distinct subgroups of these tumours (Sonic found to decrease latency and increase and traditional phenotypic monitoring.

Hedgehog/Shh, Wingless/Wnt, Group 3 penetrance of tumours. When implanted The endpoint of the study is tumour and Group 4), each arising when certain into mouse brains, these cells recapitulated development, thus time to morbidity and subsets of genes malfunction in specific Group 3 medulloblastoma histologically, Kaplan-Meier analyses will be used to assess the outcome. Morbidity will be cells within the brain. pathologically and genetically. assessed based on weight loss, ataxia and/ Previous laboratory studies have shown We were excited to see that this as yet or doming of the head. At morbidity mice that mimicking the genetic changes of unpublished research demonstrated that will be sacrificed and brains harvested Group 3 medulloblastoma in mouse neural our approach was sound, and saw this for histological analysis. Comparisons stem cells can cause these cells to behave as a great opportunity to collaborate with of survival will be made between each like that specific medulloblastoma subtype, likeminded international researchers. We oncogene and its corresponding control however this has never been shown in proposed a collaboration using the Johns cell line using a logrank test. human cells. While the mouse model Hopkins hTERT and dominant negative provides proof of principle of this concept, p53 constructs in combination with the it is important that we create models using ßcatenin, PIK3CA, N-MYC and GLI2 human neural stem cells as targeted constructs prepared in our laboratory, which therapies that will be moved forward to the Dr Eberhart enthusiastically agreed to. clinic are raised against the human genetic targets. Whilst some homology exists Unfortunately due to strict regulatory issues between human and mouse genetics, we within the Johns Hopkins Hospital, we need to ensure that we have the best, most experienced significant delays in obtaining appropriate models when these models are the constructs and the cells, and have just Figure 1: Research plan for the used to test targeted agents in order to best received the transformed cells in May of oncogenic transformation of human this year. However, during this time in our neural stem cells and subsequent predict outcomes inthe clinic. laboratory, the coding region for each target generation of mouse models of In this study, we aimed to transform normal gene (with the exception of GLI2 where we medulloblastoma. human neural stem cells into cancercausing experiences technical difficulties) has been Tumour tissue will be subjected to routine cells by altering specific genes that are amplified and cloned into separate lentiviral histopathological analyses to examine the implicated in medulloblastoma. constructs that co-express the gene types of tumours formed and confirm the These genes were selected from a list of luciferase to enable noninvasive monitoring expression of each oncogene. known mutated genes or genes found to of tumour growth using a Xenogen IVIS Furthermore, DNA and RNA will be be overexpressed in medulloblastoma, Spectrum. Each gene has also been cloned harvested from resulting tumours to including ß-catenin, the catalytic subunit into lentiviral constructs that co-express the enable molecular profiling to determine of PI3-kinase (PIK3CA), C-MYC, N-MYC green fluorescent protein gene to allow both if the tumours match the molecular and GLI2. This was to be achieved by first in vitro and ex vivo identification of tumour characteristics of the human disease.

2013 Brain Foundation Grant Hypothesis vs Findings We hypothesised that genes frequently altered in human medulloblastoma contribute to the initiation and progression of this disease. Moreover, based on evidence from mouse models, we hypothesised that normal human neural stem cells are the cell of origin for this disease. Thus, we proposed that the introduction of genes/ mutations recurrently found in human medulloblastoma to normal human neural stem cells will recapitulate tumorigenesis upon intracranial implantation into mouse brains.

Based on the findings of our collaborators at Johns Hopkins Hospital, our hypothesis was correct in the case of C-MYC overexpression in a Group 3 model of Figure 1: Research plan for the oncogenic transformation of human neural stem cells and subsequent generation of mouse models of medulloblastoma. medulloblastoma using human neural stem cells. We are currently in the process of determining if this is also the case using our genes of interest in the remaining three subtypes of medulloblastoma in our laboratory.

Figure 1: Research plan for the oncogenic transformation of human neural stem cells and subsequent generation of mouse models of medulloblastoma.

Tumour tissue will be subjected to routine histopathological analyses to examine the types of tumours formed and confirm the expression of each oncogene.

Furthermore, DNA and RNA will be harvested from resulting tumours to enable molecular profiling to determine if the tumours match the molecular characteristics of the human disease.

Figure 2: Research outcomes for the mouse models of medulloblastoma generated from the oncogenic transformation of human neural stem cells.

Figure 2: Research outcomes for the mouse models of medulloblastoma generated from the oncogenic transformation of human neural stem cells.

Hypothesis vs Findings

We hypothesised that genes frequently altered in human medulloblastoma contribute to the initiation and progression of this disease. Moreover, based on evidence from mouse models, we hypothesised that normal human neural stem cells are the cell of origin for this disease. Thus, we proposed that the introduction of genes/mutations recurrently found in human medulloblastoma to normal human neural stem cells will recapitulate tumorigenesis upon intracranial implantation into mouse brains.

Based on the findings of our collaborators at Johns Hopkins Hospital, our hypothesis was correct in the case of C-MYC overexpression in a Group 3 model of

See website for complete reports and References Winter 2016

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Look out – Zombies are rising . . . soon Zombies certainly seem to be taking over Australia.

There are now Zombie Walks in Sydney, Brisbane, Perth, Melbourne, Canberra, Fraser Coast, Cairns, Townville and Mackay has 2!

Check them out in your local area around Halloween. There are links on the Brain Foundation’s web site. You and friends can to dress up (or down) and participate or just go to enjoy the spectacle of Hollywood Horror Film characters and encourage the participants. Many have a page on My Cause and you can recognise their efforts with make-up and costumes by donating for brain research.

We thank all the organising committees who put a lot of effort in every year to this valuable area of fundraising.

Fun Runners, Think A Head!

Fun Running season is fast approaching.

In Memorium Brain Foundation offers our sincere thanks to the families and friends of the following, who donated to our research programme in their Memory.

Nigel CHAMBERLAIN Brent Charles PHILLIPS Dennis WEBBE Ian TAPP Renato BERTOSSI Fay PUTTIFOOT John ALDRICK John KING George PLESKI Denise Theresa PARR Braiden FOORD

If you are thinking of challenging yourself, or if you are a serious runner who would like to put your talents to a good cause, then please choose to support us via one of the on-line sites.

Ronald FRANKLIN

There’s a ‘spare’* brain in it for you! (*One of our great brainy caps.)

Want to be a Fabulous Fundraiser?

Do you have a cause that is close to your heart?

As you can see in this issue there are many ways you can be a Fabulous Fundraiser. But it doesn’t have to be a big event or hard work. You can set up an individual page using Go Fundraise, Everyday Hero or My Cause.

Then let your family, friends and workmates know what you are up to. These sites make it easy to update your progress and let everyone know how you are going.

Everything is taken care of for you.

Our thanks go to the following people who have used these sites to raise funds on our behalf.

Go Fundraise: Tam Ngo, John Crawford and Nicole Botica – My China Challenge Everyday Hero: Coriana Boothey, Ann Dodd, Sally Heynen, Daniel Ferguson, Chris Watson, Erica Williams, Shannon Reynolds & Kierans Crusaders, Jasmine Achille & The Pink Elephants, Sarah Moloney and Ekaterina Samsonova.

My Cause: Students at Kincoppel Rose Bay, Denise Clarke and Callum Smith

Regular Giving Would making small, regular donations suit you better than one bigger donation per year?

Perhaps you should think about making a regular monthly or quarterly donation.

Contact our office or download a form and we will do the rest for you.

Workplace Giving is an easy alternative and your company may even match your donation. Speak to your paymaster for further information.

Estate Planning and Bequests: Our benefactor, Australian Executor Trustees offers reduced rates for Brain Foundation supporters. For more information, please call Gerald in our office on 1300 886 660.

Thank you for supporting brain research through the Brain Foundation To make a donation please visit our website brainfoundation.org.au/donate or use the donation form on the letter enclosed.

Thanks to the following companies for their support: