What it feels like to have Parkinson’s disease

Initially I denied [my diagnosis] and sought second opinions. I got pretty angry. I tried to keep it secret for a while, just like Michael J. Fox did,” Palfreman says, “It took me, I’d say, about a year before I really processed it properly and then I realized that I had a destiny to use my training as a science journalist and my insights as a patient to explore this malady, which was now going to be part of my life.”

About 60,000 people each year in the US alone are diagnosed with Parkinson’s disease. Palfreman says the malady means many things that he used to do automatically, now come with much more difficulty.

“It is very much like getting on a plane and going to London and renting a car. You can drive on the left-hand side of the road, but you have to use your conscious brain to pay attention. Everything’s a bit harder. When I walk, I have to sort of consciously move my arms back and forth. Whereas, when a healthy person does it, it’s automatic. And so a lot of things that you got for free you have to work at,” Palfreman says.

The disease has three stages. The first noticeable symptoms are subtle, such as a loss of smell, constipation and possible sleeping disorders. After that, the disease attacks a person’s ability to move. The third stage produces cognitive impairment and hallucinations.

“What we classically think of Parkinson’s — the tremor, the slowness, the rigidity, the stooped gait — is really the middle act of a three-act play and that, basically, the diseases present maybe 10 or 15 years before a person gets diagnosed,” Palfreman says. “It’s a much more systemic disease than it was once thought to be.”

There are several new treatments for the disease Palfreman has been watching. One of them is based on the theory that the disease is caused by a protein, alpha-synuclein, going rogue, forming clumps called amyloids, and jumping from cell to cell, killing cells in their wake.

“If alpha-synuclein is causing all the problems, then trying to reduce the levels of it makes perfect sense, and in the next year or two, going into clinical trials, there are a number of products which are designed to sort of dissolve alpha-synuclein,” Palfreman says. “If they work, I mean the prospects are amazing. Somebody who didn’t have the disease, if you can get in early enough, would never develop the motor symptoms. And somebody like me who had the motor symptoms could possibly be stabilized so it didn’t get any worse. So there’s a lot of excitement at the moment around this.”

Palfreman says there are other things people with Parkinson’s can do to control the disease.

“The one thing which really everybody should do is regular exercise because people who do exercise and stay mobile, they do much, much, much better than people who withdraw or give up,” Palfreman says. “Because you’ve still got the conscious part of your brain, you can still drive like you’re driving into London on the wrong side of the road. It just takes a bit more energy and effort, but it still works.”

In the future, Palfreman predicts medical specialists will develop more advanced ways to control the disease.

“Just like we have very sophisticated heart pacemakers, we might get a situation where I might get an electrode in my brain and, just before my my left hand wants to set off a tremor it sets off a pulse and reboots that part of the brain. And I think these things are pretty promising so that even if you haven’t got a total cure, the management thing will become much better and we’ll be able to live pretty much essentially normal lives.”



Maintaining a Healthy Weight in Parkinson’s Disease To eat or not to eat…


By Soania Mathur, MD – Reviewed by a board-certified physician.
Progressive weight loss and undernutrition is a major feature of PD, particularly as the disease progresses. This can be due to a number of reasons. First people with Parkinson’s burn more energy due to their tremors and dyskinesias. Medications may result in nausea and loss of appetite. Neurocognitive issues such as decline in memory (forgetting to eat), depression etc. may also lead to weight loss.
Also symptoms may interfere with shopping and food preparation resulting in poor food intake.

Weight gain is also an issue for those with Parkinson’s. It is very common following surgical procedures such as deep brain stimulation which when successful improves the symptoms of PD, reducing the amount of energy burned by dyskinesias and tremors. Patients post-DBS also often describe an increase in appetite. An increase in appetite and resulting weight can also be due to medications such as dopamine agonists which can cause compulsive eating as a side effect and MAO-B Inhibitors can also cause weight gain. And patients whose symptoms of Parkinson’s are not dominated by tremors but instead slowness and stiffness will likely gain weight as well.

Good nutrition is critical in overall health and well-being and malnourishment can result in significant problems. These include a weakened immune system resulting in an increase in infections, weaker muscular strength and poor energy.

Mood issues and cognitive decline may also be consequences of poor nutritional status. And of great concern is poor bone health which when combined with the increased fall risk seen in Parkinson’s, significantly increases the chances of fractures.

So how can you maintain a healthy weight?

First of all, weigh yourself regularly so that you can detect a problem early on. Body weight is a good reflection of nutritional status. If you notice a weight loss (or weight gain) of 5 lbs. or more in a week, it is time to involve your physician.

A dietician can help design a menu that takes into consideration your weight goals and physical limitations.
Difficulty swallowing should be evaluated by a speech and language pathologist. Based on the results, a specific type of diet (food texture and size) that would be suitable can be provided.
Sometimes if there is dysphagia (difficulties in swallowing) or delayed gastric emptying (bloating and feeling overly full following a meal) it may be better to eat 5 or 6 smaller meals throughout the day instead of 3 larger meals.
Don’t waste your appetite on empty calories, i.e. foods with little nutritional value such as potato chips or candy bars. Choose instead nutritionally dense foods such as peanut butter cheese, yogurt etc.
If meal preparation is difficult for you, enlist the help of family or friends or on a good day prepare extra meals yourself that can be frozen and reheated when needed. Depending on where you live there may be government community services or private companies that deliver ready-made meals as well. And make food preparation easier by using the many easy and convenient short cuts that are available when preparing your meals. Buy precut vegetables, premarinated meats and ready made sauces. Not to mention the huge variety of fully prepared and often healthy meals that can be found in your supermarket deli, frozen food aisle or grocery store shelves. If physically getting to the store is difficult, enlist the services of a grocery delivery service

Supplementary shakes or nutritional supplements can provide much needed extra, nutritionally dense calories between meals.
Save your drinks for after or between your meals so that you don’t eat a smaller amount of nutritious foods because you’ve filled up with liquids.
Exercise. This is necessary for everyone regardless of age or health but is particularly important for those with Parkinson’s for a number of reasons including maintaining a healthy weight, increasing muscle mass and bone strength.
The amino acids in protein compete with dopamine replacement being absorbed and in some individuals this can result in poor symptom control when Parkinson’s medications are taken around a protein-rich meal. In those situations, taking medications a half hour prior to or two hours after a meal containing protein is recommended. At one time protein restriction was used to manage this issue but now it is increasingly recognized that this approach can actually result in malnourishment and weight loss. Taking medications on an empty stomach or protein redistribution may be more appropriate. In this latter scenario, protein intake is primarily included late in the day when fewer active commitments may be scheduled.
Most of these points are logical and fairly easy to incorporate into your daily routine. What they all have in common is the need to first recognize the problem and then active management of the issue. You must treat your nutritional status as an important factor in maintaining your general health and quality of life; a necessary aspect to optimize so that you are able to face the many other challenges of Parkinson’s disease.



Parkinson’s Disease: The Mystery, the Myth and the Magic


Despite its prominence in contemporary literature and the text book symptoms, diagnosis and “standard of care” treatments, there’s a lot of myth and misinformation floating around about this disease.

Plus, most of the authoritative answers are written in medical language that you need a medical degree to understand. You shouldn’t be confused about Parkinson’s simply because you didn’t go to medical school.

Parkinson’s is a condition that has been known about since ancient times. It is referred to in the ancient Indian medical system of Ayurveda under the name Kampavata. In Western medical literature it was described by the physician Galen as “shaking palsy” in AD 175. However it was not until 1817 that a detailed medical essay was published on the subject by London doctor James Parkinson.

The publication was entitled “An Essay on the Shaking Palsy.” This established Parkinson’s diseaseas a recognized medical condition. The essay was based on six cases he had observed in his own practice and on walks around his neighborhood. The essay was intended to encourage others to study the disease. Some 60 years after it was first published, a French neurologist by the name of Jean Martin Charcot did exactly that. Charcot was the first to truly recognize the importance of Parkinson’s work and named the disease after him.

Much has been learned about the disease yet much remains a mystery. The symptoms are progressive and degenerative and tend to be more common in older individuals. It is understood that a dopamine deficiency in the brain is at the root of the matter, yet why this initially occurs is less clear. It wasn’t until the 1960s that that the chemical differences in the brains of Parkinson’s patients were identified. The low levels of dopamine cause the degeneration of nerve cells in part of the brain called the substantia nigra. It was this discovery that lead to the first effective medicinal treatment of the disease. In the 1960s, the drug Levodopa was first administered to treat the symptoms and has since become the “gold standard” in medication.


Since the 1960s, research has continued to progress at a rapid rate. Despite the fact there is still no cure (The Myth), the symptoms can now be effectively controlled and reduced in severity. TheParkinson’s Disease Foundation was established in America in1957 to assist sufferers and to fund and promote further research. Many other foundations assisting the cause have been established in the following years.

A notable recent addition is the Michael J Fox Foundation, named after the much-loved television and movie actor. The foundation has been very public about its goal of developing a cure for the disease within this decade. Since its inception in 2000, it has succeeded in raising over 90 million US dollars. But it has made no more progress than for any of the other autoimmune, chronic degenerative and “incurable diseases” we posture to pursue within the convention model of what we know, what we think we know, or what we believe to be true.

Progress on all fronts is gaining momentum. Hope for the future of the “Shaking Palsy,” it seems, is decidedly solid, particularly in light of new information (almost 30 years old) that holds the promise of a paradigm shift in the fields of Neuroscience, Brain Chemistry and Quantum Physics.

Hope is a powerful thing. Without hope for a better future, no matter what the affliction, the will to live is lost and recovery is impossible.

Imagine, then, being told by your doctor that you have a progressive and degenerative disease that robs you of the ability to control your own body. A disease for which there is no cure.

This is the reality for those diagnosed with Parkinson’s disease.

Hope is offered in the form of medication such as Levodopa. Levodopa acts to restore levels of dopamine in the brain. Remember, the perceived mechanism, the lack of dopamine, is the primary reason believed to be the cause for the symptoms associated with the condition.

Consequently, many have sought hope in alternative treatments. Parkinson’s disease has been a recognized ailment in virtually all cultures since ancient times. Many of these ancient treatments are becoming popular in the west and are increasingly validated by western medicine.

Ayurvedic medicine

Alternative PD treatment

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This has been practiced in India for 5000 years.Parkinson’s symptoms are mentioned in ancient text under the name Kampavata. Ayurvedic medicine is a comprehensive system placing equal emphasis on diet, exercise, meditation, massage and herbs. One such herb, Mucuna Puriens, is gaining attention in conventional circles as its effects mimic synthetic Levodopa, with fewer side effects.

Broad beans

Australian researchers discovered that broad beans, also known as fava beans, are an extremely effective natural source of L-dopa. The highest concentration of L-dopa is found in the pod, so they are most effective when consumed whole.

St John’s Wort

Dopamine influences positive feelings in the brain, and since dopamine levels are low in Parkinson’s patients, depression is often a symptom. St John’s Wort is an herb that has been used in Europe for many years. It has been proven to be effective in alleviating depression and insomnia.

Botulinum toxin A

One of the obvious manifestations of Parkinson’s is uncontorllable movements know collectively as Dystonia. Dystonia is characterized by involuntary sustained muscle contraction resulting in repetitive movements, twisting and/or abnormal postures. Most people know of Botulinum Toxin (BTn) injections as a treatment for wrinkles; however, the true wealth in this chemical treatment is its overall effectiveness in the management of dystonia and other movement disorders when in a weak solution.

The indications for its use are expanding and now include treatment of tremor and pain, both of which are common symptoms associated with Parkinson’s. For most patients with these symptoms, BTn injections provide significant but variable relief of the symptoms that lasts for weeks to months (an average of 3 months). However, repeated injections are required to sustain benefit over long periods of time.

Coenzyme Q10 (CoQ10)

This has been shown to have an effect on the symptoms of Parkinson’s disease. However, it is unclear whether it actually slows the disease or simply temporarily alleviates symptoms. The drawback is the massive dose required.

The effective dose is approximately 1,200 milligrams a day, well above the 60 to 90 milligrams recommended by many alternative therapy advocates.


Acupuncture has bee used for centuries in China to correct energy disturbances in the body. It has become a popular method of treatment for Parkinson’s sufferers the world over. So far, there are no placebo-controlled studies that show acupuncture can treat the motor control symptoms of the disease, but there is some evidence that it can assist with sleep disturbances. There is much anecdotal evidence to suggest that it may be effective in increasing feelings of well-being and relaxation.


While not treating the Parkinson’s symptoms directly, massage can help reduce some of the discomfort associated with muscle stiffness that is commonly experienced by patients.

Alternative treatments for many diseases come and go. Some become fashionable for a short while only to be discredited and discarded. Others accumulate a growing body of scientific and popular support. It is to a large extent simply a matter of trial and error.

Nonetheless, each of these “alternatives” has as its foundation and primary goal to mimic syntheticLevodopa, with fewer side effects.


As a physician with almost 37 years of experience in clinical practice, I have had the opportunity to treat hundreds of patients with this dreaded disorder. I’ve lectured to support groups, to the Parkinson’s Association and treated the wife of the President of the local Parkinson’s Society with great success.

One of the reasons for this success is that I don’t perceive Parkinson’s as a Disease, but rather a SYMPTOM of a fundamental imbalance or deficiency rooted in areas that conventional exploration has avoided.

This simple strategy involves looking at things nobody else is looking at in ways that nobody else is looking at them in order to address the cause of the SYMPTOM rather than treating the effect of the imbalance or deficiency, i.e., the SYMPTOM.


In order to explore possible causes for the low levels of dopamine causing the degeneration ofnerve cells in part of the brain called the Substantia Nigra, we must always begin with the question, “WHY”?

In order to answer this initial question we must explore the mechanism of normal function, what’s involved in it and what could possibly alter its normal behavior.



Can drugs for Parkinson’s Disease cause uncontrollable desires?

Parkinson’s Disease is a debilitating and distressing condition, but for some the side-effects of drugs to treat it can be almost as devastating,

Compulsive desire

When Kathy, a softly spoken mother-of-two from Manchester, was diagnosed with Parkinson’s Disease she was only 44 years old. The disease, a progressive neurological condition that affects one’s ability to walk, talk and write, and inflicts debilitating tremors, normally strikes people in their 60s – only one in 15 patients in the UK are under 50 – so Kathy was unlucky. She desperately tried to hide the symptoms from the people she knew.

But then something else happened that devastated her life even more than Parkinson’s. As a suspected side-effect of the drugs she was taking, Kathy was gripped by a series of strange compulsions. Never a gambler previously, she started playing the lottery. Then, despite not knowing the rules, she became obsessed with playing poker on the internet, racking up bills of £200 a night.

She also had a powerful urge to shop, taking herself off to 24-hour superstores in the middle of the night to buy things for which she had no use; a set of new bedding, bags and bags of clothes, and CDs by artists she’d never heard of. She also developed an uncontrollable sex drive.

“I was brought up in a normal family, with proper moral standards, and I lived by those standards,” she says. “But, after I started taking the drugs, everything changed.” Kathy (not her real name) started buying fetish wear on the internet including stockings, leather and latex clothing, and arranged to meet strangers in hotels. Sometimes driving 20 or 30 miles to see them. “I was on autopilot,” she says. “I don’t even remember driving some days, but I know I did.”

Sitting at a table, listening to Kathy, now 52, talk, I find it almost impossible to connect the woman opposite me with the events she’s describing. Devoid of make-up, with blonde wispy hair and watery-blue eyes, her body is racked by Parkinson’s.

Kathy suffers from severe cramping, known as dystonia in her feet, and finds it painful to walk. Throughout our interview she has to lean heavily on her forearms to stop them from shaking.

“When I got home after that first night, having sex with a stranger, I had to talk myself out of bathing in bleach to cleanse myself,” she says flatly. “Then, the next day, the need would come back and I would do it again. I became a Jekyll and Hyde character. Every night I got the buzz and afterwards, I felt degraded.”

Kathy’s husband knew about her gambling. But he didn’t know about the sex. The couple had separate beds, and Kathy would sneak out of the house at midnight, and return home before he woke up.

Their relationship had, in fact, been deteriorating prior to Kathy’s diagnosis and the couple finally separated in 2006. Nevertheless, the break-up added to a general sense of chaos in Kathy’s life.

“I was suicidal,” she says. “Thanks to the Parkinson’s, I’d already lost control of my body. Now I felt like I was losing control of my mind”

Kathy believes her compulsions were caused by the drug ropinirole (Requip), which was prescribed for her Parkinson’s. When she finally summoned up the courage to tell her specialist Parkinson’s nurse, her dosage was reduced, and her compulsive behaviour dissipated.

Since 2003, an increasing number of Parkinson’s sufferers in the UK, America and Europe have complained of obsessive behaviour, developed after taking one of a class of drugs known as dopamine agonists such as pramipexole, cabergoline and pergolide.

“At least 14 per cent of people who take the drugs develop impulse control disorder,” says Dr Kieran Breen, director of research and development at the Parkinson’s Disease Society. His figures are based on a 2006 paper in Neurology by Valerie Voon of the National Institute of Health, in Maryland, USA. “Their behaviour changes. They become much more impulsive, but are not aware that their behaviour has changed.”

Besides an increased libido, a condition known as hypersexuality, the other side- effects are compulsive gambling, shopping and eating. In many cases, patients have spent their entire life savings; businesses have gone bankrupt; and marriages have broken down.

Researchers at London’s Hammersmith Hospital, under Professor Paola Piccini, are trying to pinpoint the reason for these side-effects but it is thought to be connected to receptors in the brain.

“In Parkinson’s disease, nerve cells die,” says Dr Breen. “These are responsible for the co-ordination of movement, something they achieve by transmitting signals from one part of the brain to another using a chemical called dopamine. When the cells start dying, you get a decrease in dopamine. Dopamine agonists are used to stimulate the dopamine receptors in the brain.

“However, depending on the type of receptor in your brain, as well as affecting the part of the brain associated with movement, the dopamine might affect the part of the brain associated with mood and compulsions.”

There is no way to predict who is most at risk of these side-effects, although Prof Piccini’s team is investigating the efficacy of various brain scanning techniques.

Aside from dopamine agonists, the other major class of drug used to treat Parkinson’s is levodopa, which is converted directly into dopamine in the brain. These drugs are far less likely, it is thought, to produce the compulsive behaviour of dopamine agonists.

“Some patients respond better to one medication than another,” says Peter Jenner, Professor of Pharmacology at King’s College, London and a fellow of the British Pharmacological Society.

“You can’t stop giving them dopaminergic drugs, because they will just become profoundly Parkinsonian,”he says.

“There is interest in the type of dopamine receptor that is responsible for these behaviours and there has been particular interest in a receptor called D3. Our problem is that we have no drugs that will selectively block the D3 receptor while still leaving the other dopamine receptors available for treating Parkinson’s disease.”

The law firm Leigh Day is preparing a class action on behalf of people who have taken roprinirole and another dopamine agonist called cabergoline. It expects to begin proceedings against the manufacturers – among them GlaxoSmithKline and Pfizer – in early 2010.

The problem, Leigh Day will argue, is not that the drugs are defective – the drugs are actually very successful at combating the symptoms of Parkinson’s – but that patients have not been warned about the side-effects.

A Pfizer spokesman says: “Evidence from spontaneous reports and certain literature suggest that pathological gambling may be a class effect of dopamine agonists. If patients or their carers are concerned about any aspect of their medication, they should consult their doctor immediately.”

Peter Middleton, a former construction manager from South Woodham Ferrers, in Essex, was diagnosed with Parkinson’s in 2002. Today, after almost seven years of compulsive gambling, he faces debts of £125,000.

“I saw two specialists and two Parkinson’s nurses, and none of them told me anything about the compulsions,” he says.

Peter, 53, would spend 20 hours at a time playing online roulette or video slot machines. And when he wasn’t using the internet, he would go to a casino.

“I maxed-out five credit cards,” he says. “I stole from my wife and my children. It’s amazing how devious you can get. How my wife stayed with me, I don’t know.”

GlaxoSmith Kline now warns about compulsive behaviour in the list of side- effects supplied with their drugs. The company says it “continues to evaluate clinical trial data, clinical trial reports, post-marketing reports and the medical literature.

“Currently, there is insufficient evidence to confirm a causal association between the development of compulsive behaviours (such as compulsive gambling) and the use of ropinirole.”

Consultants and specialist Parkinson’s nurses are being urged by the Parkinson’s Disease Society to highlight the dangers to patients. But there is still no way to predict who is most at risk.

“No matter what drug you take there are some people who will have side-effects,” says Kieran Breen. “All doctors can do is prescribe the medication if they think it’s appropriate and, if there are problems, stop it at an early stage.”

Unfortunately, for thousands of people, that advice comes far too late.


Parkinson’s is a progressive neurological condition affecting movements such as walking, talking and writing. It occurs as a result of a loss of nerve cells in the part of the brain known as the substantia nigra. These cells produce dopamine, which allows messages to be sent to the parts of the brain that co-ordinate movement. When about 80 per cent of the dopamine has been lost, the symptoms of Parkinson’s appear. Tremor, usually starting in one hand, is often the first symptom, followed by slowness of movement and stiff muscles. The cause is unknown.




parkinson’s Disease is a disorder in which sufferers lose most control of their motor skills. According to the Parkinson’s Disease Foundation, more than 10 million people across the globe are affected by Parkinson’s. We’ll give you the rundown on the disease, how it’s typically treated, and the shocking effectiveness of cannabis on those who suffer from Parkinson’s Disease.

Parkinson’s Disease Explained

Parkinson’s is an incurable disease which affects the central nervous system. The disorder causes cell death in a part of the brain that is responsible for motor control. As a result, movement becomes slow and rigid, and sufferers experience tremor and instability. This frequently results in an increase in falls, which are a source of danger for sufferers of the disease.

Cannabis Treatment for Parkinson's Disease

While the cause of Parkinson’s is unknown, experts believe that a combination of genetics and environment play a role in its development. For example, those with a family member with Parkinson’s Disease are more likely to have the disease themselves. Additionally, those who are in contact with certain pesticides, and those who have suffered head injuries, are also at increased risk.

Along with less motor control, Parkinson’s Disease can also manifest neurological symptoms. These may include:

  • Speech disorders
  • Impaired cognition
  • Depression
  • Anxiety
  • Apathy
  • Psychosis

Traditional Treatment

Because Parkinson’s Disease is incurable, treatment revolves around managing the symptoms of Parkinson’s to make life as normal as possible for sufferers. The ways in which this is achieved are varied. Levodopa is a medication commonly used to alleviate motor symptoms of Parkinson’s but comes with numerous serious side effects, including nausea, tics, joint stiffness, and “punding” (compulsive infatuation with repetitive tasks).

Brain surgery is another option, though less used, in treating Parkinson’s. It involves stimulating the brain with surgical devices to improve symptoms. Unsurprisingly, brain surgery is avoided unless necessary due to the risks associated with the procedure.

Lastly, exercise is seen as particularly important for sufferers of Parkinson’s Disease, as there is some evidence that it can improve the symptoms of the disease. Regardless, the serious risks of both standard medication and brain surgery mean finding a safer alternative is imperative for people who have Parkinson’s Disease.

Cannabis Relieves Symptoms and Treats Parkinson’s Disease

One study conducted a survey on sufferers of Parkinson’s Disease. They found that many of the subjects found relief from general Parkinson’s symptoms, improvement of tremors, reduction in slow movement, reduction in muscle rigidity, and fewer involuntary movements. Of note, fewer than 5% questioned felt that cannabis worsened their symptoms! This survey suggests that while cannabis may not alleviate all sufferers’ symptoms, it shows promise for the majority in treating their disease.

Researchers examining cannabinoids and their effects found that the chemicals in cannabis have neuroprotective qualities, particularly of a specific set of neurons in the brain. They note that this protective benefit may be relevant in the treatment of Parkinson’s Disease specifically. While there is no cure for Parkinson’s, being able to protect those neurons that the disease affects is of obvious benefit.

Another study conducted in 2014 showed even more startlingly positive results. Subjects with Parkinson’s were given cannabis to treat their symptoms. They found that motor function, reduction in tremors, and reduction in rigidity improved significantly. Additionally, quality of sleep was improved, as well as a reduction in Parkinson’s-related pain. While they note that larger studies ought to be conducted, this shows that most symptoms of Parkinson’s Disease are alleviated by cannabis.

Looking Toward the Future

Cannabis as both a treatment for symptoms of Parkinson’s Disease and for a treatment of the disease itself shows great promise. Researchers agree that more testing ought to be done for cannabis and its therapeutic benefit for Parkinson’s Disease. As it stands now, the results of further studies may very well set cannabis-based medication as a staple in treating the disease.


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Mutant fruit flies provide insight into origins of Parkinson’s disease

MRC researchers at University of Leicester investigate ‘mutant flies’

The neurodegeneration that occurs in Parkinson’s disease is a result of stress on the endoplasmic reticulum in the cell rather than failure of the mitochondria as previously thought, according to a study in fruit flies. It was found that the death of neurons associated with the disease was prevented when chemicals that block the effects of endoplasmic reticulum stress were used.

The team from the MRC Toxicology Unit at the University of Leicester. Credit: University of Leicester

Some inherited forms of early-onset Parkinson’s disease have typically been blamed on poorly functioning mitochondria, the powerhouses of cells. Without reliable sources of energy, neurons wither and die. This may not be the complete picture of what is happening within cells affected by Parkinson’s. Researchers from the MRC Toxicology Unit at the University of Leicester used a common fruit fly to investigate this further; fruit flies were used because they provide a good genetic model for humans.

Studies on human subjects are of limited use for elucidating the signaling pathways and cellular processes underlying the neurodegenerative process. This is because both ethical and technical constraints limit the extent to which genetic analysis can be performed in humans.

Flies are a well-established model animal to understand the molecular mechanisms of human diseases. This is because about 75% of human disease-causing genes are found in the fly in a similar form. Also, they are easy to work with, breed quickly and many tools are available to manipulate any genes in the fly. In flies, potential therapeutic drugs can be mixed with food and readily tested.

It was found that the bulk of the damage to neurons with damaged mitochondria stems from a related but different source – the neighbouring maze-like endoplasmic reticulum (ER).

The ER has the important job of folding proteins so that they can do the vast majority of work within cells. Misfolded proteins are recognized by the cell as being dangerous. Cells halt protein production if there are too many of these harmful proteins present. While this system is protective, it also stalls the manufacture of vital proteins, and this eventually results in the death of neurons.

To find out if ER stress might be at play in Parkinson’s, a team led by Dr Miguel Martins analyzed fruit flies with mutant forms of the pink1 or parkin genes. Mutant forms of pink1 and parkin are already known to starve neurons from energy by preventing the disposal of defective mitochondria. These genes are also mutated in humans and result in hereditary versions of the disease. Much like Parkinson’s patients, flies with either mutation move more slowly and have weakened muscles. The insects struggle to fly and they lose dopaminergic neurons in their brains – a classic feature of Parkinson’s.

Compared to normal flies, Miguel’s team found that the mutants experienced large amounts of ER stress. The mutant flies did not manufacture proteins as quickly as the non-mutants. They also had elevated levels of the protein-folding molecule BiP, a telltale sign of stress.

One function of pink1 and parkin genes is to help degrade mitofusin – a protein that tethers the endoplasmic reticulum to mitochondria. Mutant flies have an abundance of this protein. It was found that the mutants had more of their mitochondria attached to the ER than normal flies. For this reason, the researchers suggest that ER stress is related to extra tethering of mitochondria, thereby preventing the removal of defective versions of the organelle.

Mutant flies, which have more of these tethers, have fewer dopaminergic neurons, which can have an adverse effect on the brain. By reducing the number of these tethers it is possible to prevent the loss of the neurons. When the researchers experimentally lowered the amount of mitofusin in the mutants, the number of tethers fell and the neuron number increased again (see figure). The flies’ muscles also remained healthy despite the mitochondria themselves still being defective.

Image result for Mutant fruit flies provide insight into origins of Parkinson's disease

These results suggest that the neurodegeneration seen in Parkinson’s is a result of ER stress rather than a general failure of the mitochondria. The scientists were able to prevent neurodegeneration in mutant flies not only by reducing mitofusin, but also with chemicals that block the effects of ER stress.

Dr Miguel Martins said:

This research challenges the current held belief the Parkinson’s disease is a result of malfunctioning mitochondria. By identifying and preventing ER stress in a model of the disease it was possible for us to prevent neurodegeneration. Lab experiments, like this, allow us to see what effect ER stress has on Parkinson’s disease. While the finding so far only applies to fruit flies, we believe further research could find that a similar intervention in people might help treat certain forms of Parkinson’s.



Pesticide found in milk decades ago may be associated with signs of Parkinson’s

A pesticide used prior to the early 1980s and found in milk at that time may be associated with signs of Parkinson’s disease in the brain, according to a study published in the December 9, 2015, online issue of Neurology®, the medical journal of the American Academy of Neurology.

“The link between dairy products and Parkinson’s disease has been found in other studies,” said study author R. D. Abbott, PhD, with the Shiga University of Medical Science in Otsu, Japan. “Our study looked specifically at milk and the signs of Parkinson’s in the brain.”

For the study, 449 Japanese-American men with an average age of 54 who participated in the Honolulu-Asia Aging Study were followed for more than 30 years and until death, after which autopsies were performed. Tests looked at whether participants had lost brain cells in the substantia nigra area of the brain, which occurs in Parkinson’s disease and can start decades before any symptoms begin. Researchers also measured in 116 brains the amount of residue of a pesticide called heptachlor epoxide. The pesticide was found at very high levels in the milk supply in the early 1980s in Hawaii, where it was used in the pineapple industry. It was used to kill insects and was removed from use in the US around that time. The pesticide may also be found in well water.

The study found that nonsmokers who drank more than two cups of milk per day had 40 percent fewer brain cells in that area of the brain than people who drank less than two cups of milk per day. For those who were smokers at any point, there was no association between milk intake and loss of brain cells. Previous studies have shown that people who smoke have a lower risk of developing Parkinson’s disease.

Residues of heptachlor epoxide were found in 90 percent of people who drank the most milk, compared to 63 percent of those who did not drink any milk. Abbott noted that the researchers do not have evidence that the milk participants drank contained heptachlor epoxide. He also stated that the study does not show that the pesticide or milk intake cause Parkinson’s disease; it only shows an association.

“There are several possible explanations for the association, including chance,” said Honglei Chen, MD, PhD, with the National Institute of Environmental Health Sciences and a member of the American Academy of Neurology, who wrote a corresponding editorial. “Also, milk consumption was measured only once at the start of the study, and we have to assume that this measurement represented participants’ dietary habits over time.”

Chen noted that the study is an excellent example of how epidemiological studies can contribute to the search for causes of Parkinson’s disease.

This study was supported by the National Institute on Aging, the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, the Department of the Army, the Department of Veterans Affairs, and the Kuakini Medical Center.


The above post is reprinted from materials provided by American Academy of Neurology (AAN).




levodopa is a drug used to treat Parkinson's disease

An illustration of levodopa, a drug used to treat Parkinson’s disease. A biotech company is using DNA injections to help levodopa stay effective in people with advanced Parkinson’s.

A biotech company wants to fight Parkinson’s disease with a shot of healthy DNA. Voyager Therapeutics is developing a form of gene therapy that could make drugs that have lost their edge work again in people with advanced Parkinson’s.

In Parkinson’s disease, neurons responsible for making the chemical messenger dopamine die. This leads to tremors, slowness, and rigidness. Currently, people with Parkinson’s can take a drug called levodopa, or L-Dopa, to control their symptoms. But L-Dopa becomes less effective with time, as the brain loses an enzyme that converts the drug into dopamine.

With gene therapy, researchers can transplant DNA that codes for this missing enzyme. During the treatment, viruses carrying this DNA are injected into a patient’s brain through a pressurized tube.

Voyager is currently testing whether the new method can deliver enough DNA to the right brain areas to restore L-Dopa’s effectiveness.



New test looks Parkinson’s disease straight in the eye

New research suggests changes in the retina may reveal Parkinson's disease in its early stages

New research suggests changes in the retina may reveal Parkinson’s disease in its early stages (Credit: Paul Boxley)

An ability to detect Parkinson’s before it imparts irreparable damage on the brain would be a game changer when it comes to treatment options. This has inspired the development of blood tests and biosensors with the potential to pick up on the disease’s early biomarkers, and now new research has raised the prospect of a simple, low-cost eye test to catch the disease before it evolves into telltale symptoms like tremors and muscle stiffness.

Working with rats, researchers at University College London (UCL) experimented with a new imaging technique called DARC, or the detection of apoptosing retinal cells. Currently in clinical trials, DARC uses a fluorescent dye to visualize cells in the retina that are sick or dying, explains Francesca Cordeiro, a Professor of Retinal Neurodegeneration and Glaucoma Studies at UCL.

“The changes can be seen as tagged cells appearing as white fluorescent spots on the retina,” she tells New Atlas. “The number of these spots is an indicator of active disease.”

Applying the imaging technique to the animal models, the researchers found that it could reveal changes in the retina that seem to precede the disease’s more obvious symptoms, which generally start to appear once more than 70 percent of the brain’s dopamine-producing cells are destroyed.

“Our study has suggested in an experimental model of Parkinson’s that the changes identified by DARC occur early in the disease process, before the changes of dying dopaminergic cells in the brain,” says Cordeiro. “They also highlight the fact that changes in the retina can be used as an indicator of successful treatment, before changes are seen in the brain.”

Treatment options for Parkinson’s include a number of drugs designed to boost levels of dopamine in the brain, and some possible future solutions include brain-zapping headsets and other portable devices, but the UCL team treated their animal models with an anti-diabetic drug called Rosiglitazone after detecting the changes to their retinas. Following the treatment, the researchers observed clear evidence of reduced cell death in the retina and a protective effect on the brain.

Like with a lot of advances in our understanding of specific neurodegenerative diseases, the UCL team’s findings could have some widespread ramifications. The DARC method has already undergone testing in humans with glaucoma, with trials due to kick off soon for Alzheimer’s, with the researchers hopeful that it could facilitate earlier diagnoses of these conditions too.

“Nerve cell death is a feature of all neurodegenerative diseases,” explains Cordeiro. “As the eye is connected to the brain, changes in the retina reflect those in the brain. Glaucoma and Alzheimer’s therefore would have changes in nerve cell death, although they would be different in their distribution pattern and this pattern needs validation in the clinical trials.”

The findings have the researchers hopeful that it may soon be possible to intervene at much earlier stages of Parkinson’s disease, which affects a million people in the US and seven million people worldwide. It is currently working to patent the technology.

The research was published in the journal Acta Neuropathologica Communications.


University College London


Genetic engineering

Genetics and Parkinson’s Disease

Many people affected by Parkinson’s disease want to know whether it can be passed down from one generation to the next. Directly inheriting the disease is quite rare. About 10 to 15 percent of all cases of Parkinson’s are thought to be genetic forms of the disease. The other 85 to 90 percent of cases are classified as idiopathic, meaning the exact cause is unknown.

Some research shows that having a first-degree relative with Parkinson’s disease, such as a mother, father or sibling, increases your risk of Parkinson’s twofold. People with an affected first-degree relative have about a three percent lifetime risk, as compared to people in the general population who have a 1 to 1.5 percent lifetime risk. So even if Parkinson’s runs in your family, the chance of you going on to develop the disease is still very low.

To date, abnormalities in particular genes have been linked to an elevated risk of Parkinson’s disease. The three most common genes related to Parkinson’s are the following:

  • PARK2 (parkin)
  • LRRK2 (leucine-rich repeat kinase 2)
  • Glucocerebrosidase (GBA)

Mutations in the GBA gene are most common in the general population. And mutations in the LLRK2 gene are most common in certain ethnic groups, accounting for about 30 to 40 percent of Parkinson’s cases in North African Arabs and about 15 percent of Parkinson’s cases in people of Ashkenazi Jewish descent.

Even if you carry a gene mutation, it doesn’t mean you will be diagnosed with the disease. It’s not simply a mutation in one gene that matters. Experts believe that Parkinson’s disease is caused by a complex interaction of genetic and non-genetic factors.

Genetic Testing

The percentage of people with Parkinson’s who have a known gene mutation is very low, so genetic testing is not offered to every person with Parkinson’s. Usually genetic testing is done for research purposes only. The hope is that discoveries from research studies may open the door to new drug targets for Parkinson’s, or lead to tests that will determine who is at risk of developing the disease.

If Parkinson’s runs in your family and you want to get genetically tested, you should consult with a genetic counselor first. It’s a good idea to discuss the reasons for doing the testing and the impact it may have on you and your family. There are commercial companies offering genetic testing for Parkinson’s disease, but testing should be carried out by a neurologist and a counselor who specialize in genetic forms of Parkinsonism.