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NEUROLOGYneurologicalhealth.co.uk
RESEARCH IS THE KEY TO PREVENTION
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SPORT-RELATED HEAD INJURIESLooking at the link
between concussion and neurodegenerative diseases
PARKINSON’S DISEASEThe future offensive to slow or reverse this debilitating
condition
A spotlight on
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Revolutionary developments in treatment are giving hope to millions with neurological diseases
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Perception, prevention and the challenges ahead
INNOVATIVE [email protected] www.neuro-sys.fr @sysneuro
INNOVATIVE DRUG DISCOVERY FROM PLANTSNeuro-Sys is a successful neuro-pharmacological company specialised in neurodegenerative diseases such as ALZHEIMER’S, PARKINSON’S, HUNTINGTON’S and the AMYOTROPHIC LATERAL SCLEROSIS.
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Well over half of us will at some stage of our lives experience either depression, dementia, a stroke, head injury, migraine, epilepsy, Parkinson’s disease, schizophrenia, multiple sclerosis or any one of several hundred other diseases of the brain.
Neurological and psychiatric dis-eases account for about 10 per cent of the world’s over-all disease burden, and the annual
cost to the European Union alone approaches €1 trillion.
During much of the 20th centu-ry, neurological progress consist-ed mainly of describing an ever-increasing number of ways that brain function could be deranged, with scant regard to treating pa-tients. As for psychiatric disease, this remained fertile ground for speculation, little of which led to rational treatments. Our under-standing of brain disease has re-cently been revolutionised by careful neuropathology, advances in fundamental neuroscience and genetics, and by the invention of CT and MRI scans and electrical recordings to see inside the skull. Even for diseases where these methods are of limited use, well-designed clinical trials are lead-ing to improved treatments, albeit mainly for symptom control.
A major challenge is to devel-op ways of arresting the progres-sive loss of neurons that occurs in many brain diseases, including
Alzheimer’s, Parkinson’s disease, ALS (motor neuron disease) and multiple sclerosis. Although some treatments have been shown to work in animal models, clinical translation is slow and expensive. Another challenge is to maintain engagement from the pharmaceu-tical industry to invest in diseases where discoveries may take many years to emerge. Worryingly, sever-al big pharmaceutical companies have moved their research and de-velopment out of the UK, citing hos-tility to animal experimentation among reasons to do so. Others have pulled out of psychiatric disease completely, following unsuccessful clinical trials.
The British Neuroscience As-sociation supports this campaign in its aim of raising awareness of the various neurological diseases, the in-depth research carried out by the experts and the treatment options available.
CHALLENGES
Is rugby a safe sport? New
research explores the
dangers
p10EDITOR’S PICK
NEUROLOGY3RD EDITION, MARCH 2015
Managing Director: Carl SoderblomContent and Production Manager:
Cary HastingsBusiness Developer: Alex Williams
Responsible for this issueProject Manager: Sam Ayerst
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neurologicalhealth.co.uk
Dimitri KullmannProfessor of Neurology, University
College London
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INSPIRATION
Meeting the dementia research funding challenge
At the G8 leader’s meeting in De-cember 2013 the leaders of the eight nations agreed on a set of key goals to tack-
le the growing problem of demen-tia. Since then, Alzheimer’s Re-search UK has been working to-wards two aims in particular: im-proving the quality of life of peo-ple with Alzheimer’s, and finding a treatment that either cures or slows down the progression of the disease by 2025.
In the past, Alzheimer’s and oth-er dementias have suffered through
what Hilary Evans, director of ex-ternal affairs at Alzheimer’s Re-search UK, says has been a “chronic lack of investment in research”, but things are now improving. “There’s been a problem with the lack of pro-gress to find any cures or new treat-ments, but this is now being ad-dressed”, she says.
The goal is to encourage fund-ing for research and collaborations between the charity, academic re-searchers, drug companies and the UK government, says Dr Si-mon Ridley, head of research at Alzheimer’s Research UK.
“We need to explore differ-ent approaches, and new ther-apeutic avenues, and novel as well as traditional methods of looking for funding. The gov-ernment has provided support but we really need to ramp up the amount of funding from the private sources for academic
research. So we’re trying to look for investment from the pri-vate sector through a number of mechanisms.”
New collaborationsThese include the £30 million Drug Discovery Alliance, backed by the charity, which will fund three new drug discovery institutes at the uni-versities of Oxford and Cambridge and University College London. There’s also the Dementia Consor-tium, a partnership with drug com-panies Lilly, Eisai and drug devel-opment specialists MRC Technol-ogy, and a research centre in the University of Cambridge for stem cell research.
“This will allow work to flour-ish, and close the gaps between ac-ademia and industry”, Ridley says. The work could also benefit from a global fund for early-stage clinical trials, which the charity hopes will
fund promising new drugs and act as a catalyst for research.
Seeing the benefitsEvans is hopeful that these new pro-jects will make a real difference in the future. “There’s been an increase in spending on research and so hopeful-ly we will see the benefits of that soon. What we’re doing is encouraging the industry to work with academic, NGOs and the government, because there’s going to have to be a united ef-fort to make progress,” Evans says.
It’s also important to raise public awareness of Alzheimer’s, which Ev-ans says is still “relatively low” com-pared with other diseases like can-cer and heart disease. “Alzheimer’s is a disease, it’s not just a consequence of getting old, and Alzheimer’s is one type of dementia - dementias are different diseases.”
Question: What are some of the key goals for research into Alzheimer’s disease? Answer: Exploring new avenues of funding for new treatments for dementia and improving people’s quality of life.
Alzheimer’s Research UKis the world’s leading dedicateddementia research charity.Only research has the power to solve our greatest medicalchallenge and we are leading the charge for new treatments.
Find out more about our blueprint to defeat dementiaand join the fi ght at www.alzheimersresearchuk.org
Charity numbers 1077089 & SC042474
Dr Simon RidleyHead of research, Alzheimer’s Research UK
LILIAN ANEKWE
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be a way to specifically target tumours, es-pecially those of neurological origin. Evi-dence is mainly from animal studies but growing interest in using ketogenic thera-py to treat brain cancers has led to develop-ment of clinical trials of the diet alongside conventional cancer treatments. The en-hancement of mitochondrial function in-duced by the ketotic state may also be ben-eficial in disorders of neuro-degeneration such as Parkinson’s disease, Alzheimer’s disease and myotrophic lateral sclerosis. Limited evidence also suggests a protec-tive role in trauma and ischaemia, with the injured brain preferring to use ketones as a fuel. Future clinical use of ketogenic thera-py in cancer and wider neurological condi-tions must be led by well designed research trials in order to clarify who would benefit from this type of treatment and how best it should be implemented. But at almost a century old, the outlook for the ketogenic diet remains very positive; it is clearly here to stay with an exciting future ahead of it.
“The potential of ketogenic therapy to treat disorders beyond epilepsy is gaining recognition”Elizabeth Neal, Ketogenic diet research dietician
These diets are designed to induce a similar metabol-ic response to starvation, with ketone bodies be-coming the primary ener-gy substrate for brain and other metabolically active
tissues in the absence of adequate glucose supply. Worldwide scientific research on the ketogenic diet has expanded consid-erably over the past two decades and es-tablished it as a proven therapy. This plac-es it firmly alongside other treatment op-tions for intractable childhood epilepsy. Newer and more liberal variants of the di-et, the low glycaemic index treatment and the modified Atkins diet, have also been used with success. Despite considerable international and UK-wide variation in the availability of these ketogenic thera-pies, their clinical use is continuing to ex-pand to other age groups, with on-going research into the dietary treatment of epi-lepsy in young infants and adults with re-fractory seizures.
Ketogenic therapy should always be implemented with specialist medcal and dietetic supervision to ensure it is an
appropriate and safe treatment choice. This requires nutritional supplementa-tion, regular clinical monitoring and on-going dietary adjustments; aiming to maximise efficacy and minimise side ef-fects. If successful, the benefits can ex-tend beyond seizure control; anticon-vulsant medications can frequently be reduced or discontinued and improve-ments in behaviour, cognition and qual-ity of life are commonly reported. The ef-fects of the diets can be long lasting and some who have seen benefit can return to a normal diet without resumption of seizure activity.
Extended benefitsThe potential of ketogenic therapy to treat disorders beyond epilepsy is gaining rec-ognition. Already established as a first-line treatment choice for the neurometabolic diseases glucose transporter type one de-ficiency syndrome and pyruvate dehydro-genase deficiency, emerging evidence sug-gests wider applications. The preference of malignant cancer cells for glucose as an energy source suggests that this low-car-bohydrate, high-fat dietary regime could
The ketogenic diet is a high fat, restricted carbohydrate regime which has been used as a successful epilepsy treatment for almost 100 years.
NUTRICIA, SUPPORTING PATIENTS ON A KETOGENIC DIET FOR OVER 10 YEARSFor many years Nutricia has worked with dietitians, carers and the charity Matthews Friends, to help patients with intractable epilepsy and their families manage the ketogenic diet. We are committed to providing the most advanced ketogenic products and bringing the highest possible standards to epilepsy care in children.
Nutricia understands the highs and lows of caring for a child on the ketogenic diet. So to support families and carers in the little ways that matter, we offer a home delivery service to ensure the right product gets to the patient at the right time.
Nutricia Ltd.White Horse Business Park, Newmarket Avenue, Trowbridge, Wiltshire, BA14 0XQ
T: 01225 751098 www.nutricia.co.uk
Ketogenic diets and their impact on neurological diseases
INSIGHT
ELIZABETH NEAL, KETOGENIC DIET
RESEARCH DIETICIAN
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MIRACLE FOODKetogenic diets are becoming recognised as a serious treatment method for neurological disordersPHOTO: THINKSTOCK
Matthew’s Friends, the Ketogenic Diet charity in the UK, founded in 2004, supports NHS ketogenic teams as well as their patients with comprehensive Ketogenic information and resources, which is approved by our Medical Board and Clinical Staff. Treatment is also provided at Matthew’s Friends Clinics for children and adults with Epilepsy and Glut 1DS and adults with Brain Tumour. The charity and clinic also supports further research into new applications for Ketogenic dietary therapy. As hosts of the 2014 Global Symposium for Ketogenic Dietary Therapies, we are inspired by the breadth of new research and interest worldwide, broadening the scope
conditions, in addition to the known success in the treatment of refractory epilepsy.
Matthews Friends @Young Epilepsy
Main Telephone Number: 01342 836571www.matthewsfriends.org
NEWS
Despite being the most common serious neurological condition in the UK, epilepsy is still misunderstood.
Those with the condition face a postcode lottery of care. The recently published national Epilepsy12 audit revealed that although there have been some improvements in paedi-atric services, there remain ongoing concerns that children are not get-ting access to the right health pro-fessionals at the right time. Only just over half of the children in the audit had been referred to an epilep-sy specialist nurse and 57 per cent of children needing further specialist input from a paediatric neurologist were not referred on.
The World Health Organisation launched a global campaign to im-prove the epilepsy treatment gap in February 2015. ‘Epilepsy: Treat it. De-feat it.’ highlights that more than 50 million people worldwide live with the condition. But the issues that it addresses are not limited to devel-oping countries. They are the same issues that people with epilepsy face in the UK today.
Epilepsy in the spotlight
YOUNG EPILEPSY
Epilepsy training for health, education and care professionals across the UK, including masterclasses for specialists hosted by Professor Helen Cross, The Prince of Wales’s Chair of Childhood Epilepsy.
Bespoke packages including emergency medication training for schools/care homes.
For details visit youngepilepsy.org.uk
Call 01342 832243 ext 296
Email [email protected]
Got a question or need some support? Call our helpline on 01342 831342
Young Epilepsy is the national charity working exclusively to support the 112,000 children and young people in the UK with epilepsy.
Young Epilepsy is the operating name of NCYPE (National Centre for Young People with Epilepsy) Registered Charity No. 311877 (England and Wales)
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“The challenge is to wake up the cells that otherwise just sitting there dormant”Dr Alasdair Coles, senior lecturer, department of clinical neurosciences, University of Cambridge
MS comes in two forms: the relapsing-remitting form and a progressive form. Around 80 per cent of people who have MS have the relapsing-remitting form, and have periodic flare-ups of symptoms that affect their nervous system. The oth-er 20 per cent have progressive forms of MS, which cause a slow and gradual loss of their ability to do things.
The two different forms have different causes. Although we still don’t fully under-stand these differences, it appears that — put simply — the relapsing-remitting form is caused by inflammation in the brain, whereas the progressive form is caused by the slow damage and then death of nerves. This happens when a protective coat of a substance called myelin which normally protects the nerves from damage, is lost.
“In the last 20 years we have made really good strides with relapsing-remitting MS, but not for progressive MS, and the reason why is linked to their different causes”, says Dr Alasdair Coles, senior lecturer in the de-partment of clinical neurosciences at the University of Cambridge. “But we do have
an advantage, because the two forms of MS aren’t entirely connected. This means we can adopt two approaches: early treatment and experimental approaches.”
Safe treatmentEarly and aggressive treatments for relaps-ing-remitting MS means using the strong-est drugs as soon as people are diagnosed. This approach is controversial and there’s a genuine lack of consensus about whether it is safe. But the National Institute for Health and Care Excellence, which published guid-ance on how to treat MS in October 2014, is that people can be treated with stronger drugs even if they have early MS.
Coles says: “We can use early and aggres-sive treatment to stop people’s nerves from being stripped of their myelin. It’s still not standard treatment and the conservative position, which I understand, is to use mild-er drugs for people early on in the disease. At the moment there’s little evidence to say that this approach stops the progression of MS over the long-term, but that’s because we have not had the drugs for very long.”
LILIAN ANEKWE
Doctors’ knowledge of the different causes of multiple sclerosis is leading to new potential for treatment and research, according to leading University of Cambridge expert, Dr Alasdair Coles.
What does the future hold for MS research?
NEWS
Another approach would be to look at the possible potential of giving people with MS drugs that can restore the myelin that dam-aged nerve cells have lost. “There’s promis-ing lines of research, although nothing yet that’s in the clinic”, Coles says.
“We know there are stem cells in the brain that are capable of being remyelinat-ed. So the challenge is to wake up the cells that that otherwise just sitting there dor-mant” says Coles, who is conducting an early-stage trial looking at using existing MS drugs in this way.
So the current research efforts in MS mean that in the future people with MS could benefit from a combination ap-proach, to combat the inflammation and to regenerate stem cells and repair the nerves — and possibly leading to better management of MS.
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RESEARCH IS KEYUnderstanding the causes behind this unpredictable disease will prove key in treating it.PHOTO: THINKSTOCK
FACTS ON MS
51
There are more than 100,000 people in the
UK currently living with MS.
2Symptoms usually start in your 20s and
30s and it affects almost three times as many women as men.
3It affects the central nervous system — the
brain and spinal cord nerves which control bodily functions. The immune system attacks the myelin coating which protects nerve fibres, damaging the nerves and causing them to malfunction.
4MS is an unpredictable c o n d i t i o n a n d
symptoms include problems with mobility and balance, vision and dizziness, fatigue, bladder problems, muscle stiffness and depression.
5The MS Society is the UK’s leading MS charity; we
provide information and can help people – call our helpline on 0808 800 8000 or visit www.mssociety.org.uk
MS SOCIETY
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“When we also consider the fami-lies of people struggling with the disease this means Parkinson’s di-rectly affects 20-40 million people. Parkinson’s also affects govern-ments and healthcare systems be-cause it is a very complex condition to treat as each person has their own combination of symptoms”, Dr Wyse, says.
The Cure Parkinson’s Trust is working with neurology experts worldwide, and has identified more than 70 potentially disease-modi-fying’ treatments. The Trust has al-ready prioritised more than 20 of these radical new treatment ap-proaches to be tested in PD patients in specialist neurology hospitals around the world.Dr Wyse explains: “The first of these trials, involving repurposing of an anti-diabetic drug, was com-pleted last year with extremely
promising results suggesting we may have already intercepted de-cline in PD patients.”
A second line of new treatments involves several ‘mitochondrial’ targeted drugs.
“We are starting to move towards developing personalised medicine for PD patients, with future thera-pies matched to their genetics, bi-ochemistry, and their symptoms”. As such they have identified po-tential treatments targeting a wide range of biochemical pathways which now need to be proven in clinical trials.
Regenerative medicineAnother key area is regenerative medicine, focusing on re-grow-ing and replacing the cells that have died as Parkinson’s progress-es. “Surgical trials of transplanta-tion of neural tissue, and of long-term infusions of a natural brain growth factor, GDNF, are underway in Cambridge and Bristol, and offer huge promise.” The neurodegen-erative disease named after James Parkinson who discovered it in 1817, includes a range of crippling mo-
tor and non-motor symptoms such as shaking, slowness of movement, gut problems and disturbed sleep.
According to Dr Wyse, the main causes of Parkinson’s are environ-mental, such as exposure to pesti-cides or in manganese mines; ge-netic (about 10 per centπ of patients have genetic forms of PD), and for others it’s triggered by head trauma, as in the case of the famous boxer Muhammed Ali.
All current treatments just fo-cus on managing daily symptoms. Since some people are diagnosed with the disease in their 30s or 40s they can be afflicted with the disease for 40 to 50 years.
Dr Wyse and his colleagues are working hard on finding a cure be-yond symptomatic treatments. He says: “While money is current-ly needed to test many innova-tive new disease-modifying treat-ments in the clinic we believe there really is hope that in the near fu-ture we can slow, stop and even reverse Parkinson’s.
DIANE [email protected]
Dr Richard Wyse Director of research and development, The Cure Parkinson’s Trust
INSPIRATION
Real promise for 10 million people living with Parkinson’s
Dr Richard Wyse, director of research and development at The Cure Parkinson’s Trust, believes that “scientifically, now more than ever, there is considerable hope about future therapies to slow, stop or reverse Parkinson’s.”
B r i t a n n i aP h a r m a c e u t i c a l s L t d
BRITANNIA PHARMACEUTICALS IS PROUD TO SUPPORT MEDIAPLANET ON PARKINSON‘S
What are the most promising new approaches that are helping researchers to better understand the effects of Parkinson’s disease (PD)? Professor Roger Barker, who works at the University of Cambridge’s centre for brain repair, explains. “Three areas of complimentary research are contributing to researchers gaining a better understanding of PD and the right treatments for different people”, Barker says.
“At the moment we don’t really under-stand why some people do well for many years while others quite quickly develop serious effects. We’re trying to learn why from looking at the genetic makeup of people who have more aggressive diseas-es. We can take their skin cells and repro-gram them in the lab and convert them into nerve cells. Then we can discover new targets for research and treatments.”
“The future will come when we are able to take embryonic cells and turn them in-to new nerve cells, and inject them into the brains of people with PD. It won’t be a cure but it could vastly improve symp-toms for 10 or even 20 years. There’s some research now in mice that is promising, and I hope to see results in the next five years. There’s focus on a protein called al-pha synuclein, which builds up inside the brain cells of people with PD and spreads outside of the brain. It’s a completely new idea, but if proven we might be able to de-velop a vaccine to stop the symptoms.”
New approaches to Parkinson’s research
LILIAN [email protected]
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NEWS
Revolutionary treatment for brain tumours
Professor Lars Leksell, who wanted to emu-late the surgical pre-cision of a scalpel with beams of radia-tion, fi rst developed the tool 40 years ago.
He developed the Gamma Knife as a dedicated tool, able to deliver a highly accurate therapeutic dose of radiation to the brain with little or no harm to the patient, and it has become the gold standard of stereo-tactic radiosurgery (SRS).
Professor Christer Lindquist, Consultant Neurosurgeon at the BUPA Cromwell Hospi-tal Gamma Knife Centre in Lon-don worked with the late Prof Leksell in research and develop-ment of the Gamma Knife and has the longest experience with the device worldwide.
He says: “The Gamma Knife was a quantum leap for the treatment of many inoperable brain tumours and other conditions when it was fi rst introduced.
“A very high dose of radiation is delivered in one single treatment session, and the patient can be treated as an outpatient or stay only one night in the hospital.
“The high dose is, however, tox-ic not only to the treatment ob-ject but it may also be injurious to normal brain. It is therefore
essential that the radiation vol-ume is “tailor-made” to the ob-ject to be treated.”
Salvage therapyProf Lindquist came to London in 1998 from the Karolinska Hospi-tal in Stockholm, where he was
the Director of the Skull Base Surgery Program and the Gamma Knife Center in the Department of Neurosurgery and has pub-lished some 100 scientific papers in neurosurgery.
He says: “Whole Brain Radia-tion Therapy (WBRT) is the most common type of radiation still used in the UK to treat brain me-tastases. In my opinion it should now only be used as salvage ther-apy. Side effects such as memo-ry deficits, dementia and epilep-tic seizures are not acceptable when modern radiosurgery is a better treatment.”
The Leksell Gamma Knife can be used to treat primary and sec-ondary brain tumours, and some cases of Parkinson’s Disease, epi-lepsy and Obsessive Compulsive Disorder (OCD).
The one-day non-invasive treatment means patients can usually receive treatment in a single day and return to normal lifestyle the day after treatment. More than 800,000 patients have been treated with the gamma knife throughout the world.
People with brain tumours can now be treated with a gentler alternative to surgery with a remarkable ‘gamma knife’.
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ProfessorChrister Lindquist Consultant neurosurgeon, BUPA Cromwell Hospital,Gamma Knife Centre, London
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RADIATION TREATMENTPatients can receive the gamma knife treatment and return to normal life the next day.
10 · neurologicalhealth.co.uk
Physical exercise helps keep brains healthy but acute concussion, a brain injury that can go undetected, can be fatal. Repeated concussions are known to cause neurodegener-ative disease in boxers. Could rugby players suffer in the same way?
To find out Professor Damian Bailey of the Neurovascular Re-search Laboratory at the Univer-sity of South Wales has developed tests that focus on the brain’s con-trol of it’s own blood flow and oxy-gen. Bailey says: “Understanding of the causes and long-term brain ef-fects of concussions is poor. Concus-sions can be hard to spot, do not re-quire a direct blow to the head and in 90 per cent of cases do not lead to unconsciousness.
“We have found evidence of accel-erated brain ageing leading to im-paired mental agility and dementia symptoms in retired rugby players.”
Bailey has put over 250 rugby players through tests designed to challenge the brain. Putting the
brain under pressure through novel types of exercise, high-fat meals and changes in oxygen/car-bon dioxide has detected subtle and enduring signs of brain injury. Study participants were matched against non-rugby playing con-trols of similar age and fitness. The findings are being submitted for scientific publication.
“Our research could change the way rugby is played and even the game’s rules, so accurate results are essential,” says Bailey. “We believe that our battery of lab tests can pick up subtle effects and provide a more scientific means of determining when the brain has fully recovered - or not, as we have seen in some of the sedentary retired players. Our ap-proaches include electron paramag-netic resonance spectroscopy and ozone-based chemiluminescence to measure blood levels of free radicals, tiny molecules that in excess can damage the brain and impair blood flow and oxygen delivery.”
The lab also uses high-performance data acquisition hardware to cap-ture a wide varie-ty of signals from the brain, heart, lungs and mus-cles. This includes blood flow and oxy-genation, blood pressure, heart rate, ventilation and the composition of expired gases.
Bailey says: “If my re-search confirms there is a clear risk of brain injury from concussions I hope it will be used to inform return to play decisions and help prevent some of the more damaging long-term chang-es to the brain that can oc-cur when players retire.”
LINDA WHITNEY
Scientists are using new techniques to study the effects of concussion in rugby players which could make the sport safer and give insights into neurodegenerative diseases.
One in six people in the UK suffer from a neurological disorder. This can be from birth, through a slowly developing illness or through brain injury.
The National Brain Appeal is the charity dedicated to raising much-needed funds for The National Hospital for Neurology and Neurosurgery. We rely on your donations to fund vital research and projects.www.nationalbrainappeal.org Registered charity no: 290173
IS RUGBY A SAFE SPORT? NEW STUDIES ARE HELPING RESEARCHERS FIND OUT
INSPIRATION
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www.braintumourresearch.orgTel: 01296 733011 | [email protected]
BRAIN TUMOURS KILL MORE CHILDREN AND ADULTS UNDER THE AGE OF 40 THAN ANY OTHER CANCER
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