EFFECTS OF HIGH RISK PARKINSONS MUTATIONS 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.

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.

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.

POMEGRANATE DRUG TO AID ALZHEIMERS PARKINSONS DISEASE

Dr Olumayokun Olajide's research will look to produce compound derivatives of punicalagin for a drug that would treat neuro-inflammation and slow down the progression of Alzheimer's disease

The onset of Alzheimer's disease can be slowed and some of its symptoms curbed by a natural compound that is found in pomegranate. Also, the painful inflammation that accompanies illnesses such as rheumatoid arthritis and Parkinson's disease could be reduced, according to the findings of a two-year project headed by University of Huddersfield scientist Dr Olumayokun Olajide, who specialises in the anti-inflammatory properties of natural products.

Now, a new phase of research can explore the development of drugs that will stem the development of dementias such as Alzheimer's, which affects some 800,000 people in the UK, with 163,000 new cases a year being diagnosed. Globally, there are at least 44.4 million dementia sufferers, with the numbers expected to soar.

The key breakthrough by Dr Olajide and his co-researchers is to demonstrate that punicalagin, which is a polyphenol -- a form of chemical compound -- found in pomegranate fruit, can inhibit inflammation in specialised brain cells known as micrologia. This inflammation leads to the destruction of more and more brain cells, making the condition of Alzheimer's sufferers progressively worse.

There is still no cure for the disease, but the punicalagin in pomegranate could prevent it or slow down its development.

Dr Olajide worked with co-researchers -- including four PhD students -- in the University of Huddersfield's Department of Pharmacy and with scientists at the University of Freiburg in Germany. The team used brain cells isolated from rats in order to test their findings. Now the research is published in the latest edition of the journalMolecular Nutrition & Food Research and Dr Olajide will start to disseminate his findings at academic conferences.

He is still working on the amounts of pomegranate that are required, in order to be effective.

"But we do know that regular intake and regular consumption of pomegranate has a lot of health benefits -- including prevention of neuro-inflammation related to dementia," he says, recommending juice products that are 100 per cent pomegranate, meaning that approximately 3.4 per cent will be punicalagin, the compound that slows down the progression of dementia.

Dr Olajide states that most of the anti-oxidant compounds are found in the outer skin of the pomegranate, not in the soft part of the fruit. And he adds that although this has yet to be scientifically evaluated, pomegranate will be useful in any condition for which inflammation -- not just neuro-inflammation -- is a factor, such as rheumatoid arthritis, Parkinson's and cancer.

The research continues and now Dr Olajide is collaborating with his University of Huddersfield colleague, the organic chemist Dr Karl Hemming. They will attempt to produce compound derivatives of punicalagin that could the basis of new, orally administered drugs that would treat neuro-inflammation.

Dr Olajide has been a Senior Lecturer at the University of Huddersfield for four years. His academic career includes a post as a Humboldt Postdoctoral Research Fellow at the Centre for Drug Research at the University of Munich. His PhD was awarded from the University of Ibadan in his native Nigeria, after an investigation of the anti-inflammatory properties of natural products.

He attributes this area of research to his upbringing. "African mothers normally treat sick children with natural substances such as herbs. My mum certainly used a lot of those substances. And then I went on to study pharmacology!"

Role of physiotherapy in Parkinsons Disease

Parkinson's Disease

Parkinson’s disease is really a condition in which the amounts of chemical messengers in the brain are reduced. Many times, it causes reducedmobility, memory problems, muscle tremors, and difficulties performing everyday tasks. Physiotherapy for those who have Parkinson’s disease concentrates on increasing and looking after mobility whilst lowering the risk of falls.
Physio provide neurological physiotherapy treatment specific towards the needs of the individual. Our specialist physiotherapists know how Parkinson’s affect an individual and people close to them. Consequently, the majority of patients with Parkinson’s are noticed in their home environment with partners, relatives or carers present. 
Parkinson's disease affects approximately One in 500 of the general population. It's a progressive neurological condition affecting activities for example walking, talking, and writing.
Parkinson's disease occurs as a consequence of a reduction of nerve cells within the part of the brain referred to as substantia nigra. These cells have the effect of producing a chemical referred to as dopamine, which assists in the transmission of messages delivered to the parts of the brain that co-ordinate movement. Using the significant reduction in the amount of dopamine-producing cells, these areas of the brain are unable to function normally.
Classify the results of Parkinson's disease as motor and non-motor. 
Common motor symptoms observed in Parkinson's disease are:
• Tremor - usually begins in a single hand (the first symptom for 70% of individuals with Parkinson's disease).
• Slowness of motion - people with Parkinson's disease usually see that they have difficulty initiating movements or that performing movements takes longer.
• Stiffness or rigidity of muscles - individuals with Parkinson’s disease often find they have problems with activities for example standing up from a chair or allowing this to continue in bed.
• Postural instability - results in impaired balance and falls.
• Gait and posture disturbances:
o Shuffling gait.
o Decreased arm swing
o Stooped, forward-flexed posture
o Gait freezing - happens in tight, cluttered spaces, doorways or when initiating gait
• Other motor symptoms:
o Fatigue
o Mask-like, expressionless face with infrequent blinking
o Micrographia (small, cramped handwriting)
Various non-motor symptoms can also be experienced, for example:
• Sleep disturbance
• Constipation
• Urinary urgency
• Depression
Treatment for Parkinson’s Disease
While there is no cure for Parkinson's disease at the moment, drugs are used to attempt to control the symptoms. Within the majority of newly diagnosed people considerable improvements is possible by careful introduction of anti-Parkinson drugs. When only mild symptoms can be found, individuals may decide, along with their GP/consultant, to delay medications until their symptoms increase and instead depend on a healthy lifestyle, focusing on exercise, relaxation and diet. As Parkinson's disease is an extremely individual condition medicine is prescribed and adapted to individual needs. Reaction to medication varies from individual to individual and not every medication is going to be considered suitable for everyone.
Kinds of medication commonly used are:
• Levodopa
• Dopamine agonists
• COMT inhibitors
• MAO-B inhibitors
• Glutamate antagonists
• Anticholinergics
Surgery
Surgical treatment is available for some people with Parkinson’s disease, determined by symptoms. This includes:
• Deep brain stimulation
• Lesioning
Parkinson’s Disease Physiotherapy Treatment
Physiotherapy is essential in the management of Parkinson’s disease. Individuals with Parkinson’s disease usually have mobility problems and therefore are often at high-risk of falls. Physio try to increase mobility and recommend changes to the home environment to improve independence and safety. Consequently, patients with Parkinson’s disease can cope better from day-to-day and keep their independence.
Independence is increased with balance, stretching and strengthening exercises and provision of walking aids and equipment. Our physiotherapists will assess how a person performs activities for example; walking, going up and down stairs, getting away from a chair and becoming in and out of bed. Our physiotherapists canteach patients, their loved ones and carers, special strategies how do deal with common the signs of Parkinson’s. Family and carers usually see this advice and the practical handling techniques particularly helpful, with regards to helping individuals up out of bed, walking and overcoming freezing. 
Physio recommend a house assessment is performed so advice could be given regarding any changes which may be required. This will boost the safety and independence from the patient with Parkinson’s disease. In the home assessment our physiotherapists will give you advice and suitable tips about aids and adaptations to increase the independence and safety from the patient.
A specific falls prevention programme can be produced to be completed between treatment sessions. The house assessment, along with a falls prevention programme, will greatly increase safetyat home and lower the risk of falls.
Physio offer acupuncture,hydrotherapy, seating / wheelchair assessments and suggestions about postural management for people with Parkinson’s disease. Patients with Parkinson’s disease often enjoy physiotherapy because it increases their independence and reduces their anxiety about falling.