New lead for potential Parkinson’s treatment: Effects of high-risk Parkinson’s mutation are reversible

Researchers from the University of Sheffield have found vital new evidence on how to target and reverse the effects caused by one of the most common genetic causes of Parkinson’s.

Mutations in a gene called LRRK2 carry a well-established risk for Parkinson’s disease, however the basis for this link is unclear.

The team, led by Parkinson’s UK funded researchers Dr Kurt De Vos from the Department of Neuroscience and Dr Alex Whitworth from the Department of Biomedical Sciences, found that certain drugs could fully restore movement problems observed in fruit flies carrying the LRRK2 Roc-COR Parkinson’s mutation.

LRRK2A microscope image of a cultured cell

These drugs, deacetylase inhibitors, target the transport system and reverse the defects caused by the faulty LRRK2 within nerve cells. The study is published today (15 October 2014) month in Nature Communications.

Dr De Vos, a Lecturer in Translational Neuroscience at the world-leading Sheffield Institute for Translational Neuroscience (SITraN), said: “Our study provides compelling evidence that there is a direct link between defective transport within nerve cells and movement problems caused by the LRRK2 Parkinson’s mutation in flies.”

Co-investigator Dr Alex Whitworth explained: “We could also show that these neuronal transport defects caused by the LRRK2 mutation are reversible.

“By targeting the transport system with drugs, we could not only prevent movement problems, but also fully restore movement abilities in fruit flies who already showed impaired movement marked by a significant decrease in both climbing and flight ability.”

The LRRK2 gene produces a protein that affects many processes in the cell. It is known to bind to the microtubules, the cells’ transport tracks. A defect in this transport system has been suggested to contribute to Parkinson’s disease. The researchers have investigated this link and have now found the evidence that certain LRRK2 mutations affect transport in nerve cells which leads to movement problems observed in the fruit fly (Drosophila).

The team then used several approaches to show that preventing the association of the mutant LRRK2 protein with the microtubule transport system rescues the transport defects in nerve cells, as well as the movement deficits in fruit flies.

Dr De Vos added: “We successfully used drugs called deacetylase inhibitors to increase the acetylated form of α-tubulin within microtubules which does not associate with the mutant LRRK2 protein. We found that increasing microtubule acetylation had a direct impact on cellular axonal transport.
“These are very promising results which point to a potential Parkinson’s therapy. However, further studies are needed to confirm that this rescue effect also applies in humans.“

Dr Beckie Port, Research Communications Officer at Parkinson’s UK, which helped to fund the study, said: “This research gives hope that, for people with a particular mutation in their genes, it may one day be possible to intervene and stop the progression of Parkinson’s.

“The study has only been carried out in fruit flies, so much more research is needed before we know if these findings could lead to new treatment approaches for people with Parkinson’s.”

Additional information

Godena V K et al (2014) ‘Increasing Microtubule Acetylation Rescues Axonal Transport And Locomotor Deficits Caused by LRRK2 Roc-COR Domain Mutations’. NatComms

About Parkinson’s UK
Every hour, someone in the UK is told they have Parkinson’s.
It affects 127,000 people in the UK – which is around one in 500 of the population.
Parkinson’s is a degenerative neurological condition, for which there currently is no cure. The main symptoms of the condition are tremor, slowness of movement and rigidity.
Parkinson’s UK is the UK’s leading charity supporting those with the condition. Its mission is to find a cure and improve life for everyone affected by Parkinson’s through cutting edge research, information, support and campaigning.
For advice, information and support, visit or call our free, confidential helpline on 0808 800 0303.

The Sheffield Institute for Translational Neuroscience (SITraN)
SITraN is a world-leading centre for research into neurodegenerative diseases including motor neurone disease (MND/ALS), Parkinson’s disease and Alzheimer’s disease. The purpose-built facility uniquely allows the multidisciplinary collaboration of clinicians, scientists and health professionals to develop new treatments for the benefit of patients.
To find out more visit

The University of Sheffield

Dopamine cell therapy for Parkinson’s shows promise

Just one shot of dopamine cells derived from stem cells could be enough to reverse many of the features of Parkinson’s disease for decades – and the barriers to developing such a treatment are finally being overcome

Professor Roger Barker has a dream: by the time he retires in 15 years, he would like to see for Parkinson’s disease available on the NHS.

Fifteen years may seem like plenty of time to realise this dream, but there are so many contingencies that even he admits this may be optimistic. “It assumes that all our clinical trials go smoothly, that industry takes up the technology – and that ‘stem cell tourism’ doesn’t set us back,” he said.

It’s not difficult to understand why people resort to stem cell tourism – going abroad, usually to countries such as India and China, to receive private, unregulated stem cell therapies (however experimental) to treat incurable conditions such as Parkinson’s or multiple sclerosis. There has been much hype surrounding stem and, with nothing to lose, isn’t it worth at least trying one of these treatments? The trouble is that they are based on very limited – if any – evidence and have the potential “to go pear-shaped”, said Barker. This could damage public – and, more importantly, regulators’ – confidence in the field and lead to inappropriate restrictions on legitimate research.

The idea of cell transplants to treat Parkinson’s is not new. One of the key characteristics of the disease, which affects around one in 800 people by the time they are elderly, is the death of dopamine-producing cells in the brain. Finding a way to replace these cells could, in theory, lead to dramatic improvements in the patient’s health.

An adult typically has around half a million dopamine cells in the substantia nigra on each side of the brain. When half of these cells have died, the patient will begin showing symptoms, which include a resting tremor, slowness of movement and rigidity. “One of the reasons Parkinson’s disease is so attractive for cell therapies,” explained Barker, “is that it is a tractable problem. If we can get just 100,000 proper nigral dopamine cells in there, it should make a difference.”

Ever since the 1980s, scientists have been trialling ways of replacing dopamine cells with cells taken from aborted fetuses – a practice which, aside from ethical concerns, is not practical on a scale needed to treat the hundreds of thousands of patients in the UK alone.

The trials had mixed success. In some, patients continued to see improvements over 15 years; however, in others, the treatment not only failed, but patients suffered side effects. In part, this was due to an inconsistency in protocols, for example the age of participants, the clinical techniques used for cell delivery and the number of cells transplanted.

Now, with funding from the European Union, Barker and collaborators in Europe have developed a protocol that is more likely to provide safe, consistent and clinically effective benefits for patients. He is leading a trial in Europe to use to treat patients, with the aim of “putting cell therapies for Parkinson’s disease back on the map.”

If the trial is successful, by 2018 the researchers hope to begin trialling the use of dopamine cells derived from through a new collaboration with teams across Europe, the USA and Japan. (The collaborators in Japan hope to conduct a similar trial using induced – the patients’ own skin cells, reprogrammed to become stem cells.)

The beauty of using stem cells is that they can be programmed to become almost any type of cell within the body. The risk, of course, is that they become the wrong kind of cell or ‘run away with themselves’ to become cancerous. Earlier this year in Lisbon, an experimental stem cell treatment – part of an approved trial to cure paralysis – reportedly led to a paraplegic woman growing a nasal tumour on her back. However, Barker is confident that new protocols have all but eliminated safety concerns – though this risk may be very real in cases of stem cell tourism.

It has still been a challenge to programme the stem cells to become nigral dopamine cells. “You take stem cells and programme them to become ‘neural ‘. These cells make brain; some will turn into dopamine cells and others will want to become forebrain – but if you already have a forebrain, growing another one is not going to help you! Fortunately, we’ve found a way round this to allow us to commit the precursor cells to become the right dopamine cells without the other cells appearing after grafting.”

Pre-clinical studies in mice have shown success in treating Parkinson’s disease with dopamine cells derived from , but the mice are observed only over a matter of months: Parkinson’s, by contrast, is a disease that progresses over decades. Indeed, postmortems of some of the people who had previously received fetal cell transplants found evidence of the disease in some of the cells in the graft as though the protein involved in Parkinson’s had caused disease in the transplant. “If that’s the case, then even with stem cell therapies we could start to see pathology. But even if that is true, we know it will be decades before we start to see an effect and so this should not prevent them being adopted for treating patients.”

“Of course, just because we can do something doesn’t necessarily mean we should,” added Barker. Treatments already exist for Parkinson’s disease. The drug L-dopa can replace lost dopamine and reverse symptoms – but medication needs to be taken regularly, can cause side effects and eventually becomes relatively ineffective. Deep brain stimulation – electrodes implanted into the brain – can likewise prevent tremors and reduce some of the motor features experienced by Parkinson’s sufferers, but patients need to carry around battery packs under their skin. Cell therapies, on the other hand, are relatively straightforward to administer, injected through a small hole in the skull, and just one shot should last decades.

Even so, Barker is realistic about what can achieve. “They are likely to be no more effective than existing treatments. We certainly won’t be curing anyone.” He is also aware that to produce cells on a scale large enough for widespread use, the technology will need to be picked up by industry. “And once this becomes a commercial treatment, price may become the biggest issue.”

Yoga Hope for Parkinson’s Patients

The sad news of beloved comic Robin William’s death was followed by reports he was fighting Parkinson’s disease.  His widow, Susan Schneider, revealed the star struggled with depression and anxiety during the early stages of the disease.  Parkinson’s disease is a degenerative brain disorder that is caused by nerve cell degeneration in a region of the brain that controls voluntary movement. The symptoms include tremors, a shuffling walk, muscle stiffness, stooped posture, and a mask-like, expressionless face. Other non-motor symptoms include depression, dementia and cognitive impairment.  In memory of Robin Williams, here are ways yoga practice can help people with Parkinson’s disease.

Continue reading

Researchers work to find treatments for Parkinson’s

Not long after actor and comedian Robin Williams’ Aug. 11 suicide, fans learned that the 63-year-old Oscar winner had recently been diagnosed with Parkinson’s disease.  In the days following Williams’ death, his widow, Susan Schneider, revealed the news and maintained the actor — who had struggled with substance abuse since the 1980s and checked into rehab this summer to maintain sobriety — was sober at the time of his death.  “Robin’s sobriety was intact and he was brave as he struggled with his own battles of depression, anxiety as well as early stages of Parkinson’s disease, which he was not yet ready to share publicly,” she said in a statement.  While Parkinson’s disease is common, said Jerry Henberger, executive director of the Parkinson’s Association of San Diego, it’s also misunderstood.

Continue reading

Parkinson’s therapy aims to help retrain brains

BRIDGEWATER, Pa. (AP) — Parkinson’s robs people of the ability to control their movements, but some patients in Beaver County are seeing big results from a physical therapy program designed to counteract the symptoms of the degenerative disease.

While there is no cure for Parkinson’s disease and little is known about the cause, experts know that people with the nervous system disorder have trouble with slowness of movement, and their movements are also small, said Dale Reckless, facility director of M-R-S Physical Therapy in Bridgewater.

But the Lee Silverman Voice Treatment Big (LSVT Big) therapy program, which Reckless brought to M-R-S and Beaver County earlier this year, is aimed at keeping people’s movements big and quick in order to counteract those symptoms.

Continue reading

Research targets early symptoms of Parkinson’s

University of Adelaide neuroscience researchers are investigating markers for potential earlier diagnosis and treatment of Parkinson’s disease.  The researchers are studying the molecular basis of non- of Parkinson’s disease, rather than the better-known clinical symptoms of impaired movement. These “non-motor” symptoms include , depression and anxiety – and they can appear several years before the emergence of motor symptoms.


Continue reading

Dutch MedTech Startup Team Brings Fresh Hope For Sufferers Of Parkinson’s Disease

Timing is everything in business; especially where groundbreaking medical treatments, investments and acquisitions are concerned.  So when a pioneering med-tech start-up comes up with a new treatment for Parkinson’s disease – effectively a next generation pacemaker for the brain – the business and investment world takes notice.

Continue reading

World Parkinson Coalition to Hold Online Conference

The World Parkinson Coalition (WPC) is hosting its first ever WPC Scientific Update online for free September 30 to October 1.

WPC Scientific Update: Parkinson Pipeline Umbrella will take place over three days in six one-hour sessions at 12 p.m. ET/9 a.m. PT and at 2 p.m. ET/ 11 p.m. PT. In addition to the live webcast, the sessions will archived for later viewing.

Sessions will be about the latest scientific updates from the Parkinson’s research world. Thefull program is available online. Participants are also encouraged to tweet before and during the sessions using the hashtag #WPCwebcast.

For more information and to register, click here.

NeuroDerm Starts Phase 2a Study of Parkinson’s Drug

NeuroDerm Ltd., a clinical stage pharmaceutical company developing drugs for central nervous system (CNS) diseases, announced that the first patients with severe Parkinson’s disease have been enrolled and dosed in a Phase 2a trial of ND0612H. ND0612H is a high-dose form of NeuroDerm’s proprietary liquid levodopa/carbidopa (LD/CD) drug formulation, delivered continuously through subcutaneous administration by a belt-pump.

Entia Biosciences Awarded Grant from Michael J. Fox Foundation

Entia Biosciences Inc. (OTC: ERGO), an emerging leader in the field of nutrigenomics, was recently awarded a grant from the Michael J. Fox Foundation to conduct a preclinical study evaluating its ErgoD2® medical food as a potential therapy for the treatment of Parkinson’s Disease. Approximately 60,000 Americans are diagnosed with PD each year, with an estimated one million living with the disease.

To syndicate this article, or for more information, please contact us online or call (406) 862-5400.

Continue reading

Link Between Parkinson’s Disease And Creativity

Tel Aviv University

New TAU study confirms creative energy in Parkinson’s sufferers is greater than in healthy individuals

Prof. Rivka Inzelberg of Tel Aviv University’s Sackler Faculty of Medicine and the Sagol Neuroscience Center at Sheba Medical Center, Tel Hashomer, documented the exceptional creativity of Parkinson’s patients two years ago in a review for Behavioral Neuroscience. Since then, she has conducted the first empirical study to verify a link between Parkinson’s disease and artistic inclination.

Continue reading