JPD Blog

In this section of the JPD blog, Jon Palfreman contributes news of interest to the PD research community, in the form of short opinion items and regular blog posts.

 

16 January 2014

New Research Suggests Changes in Parietal Brain Gray Matter Volume Associated with Memory Deficits in Early PD

Research by a team of investigators in Finland suggests that the free recall memory deficits common even in early stages Parkinson’s disease (PD) are related to structural changes in the brain, specifically parietal cortical gray matter volume. Their findings are published in the current issue of the Journal of Parkinson’s Disease.

Beyond the Snapshot

Every parkie is interested in knowing the answer to the question: “how am I doing?” We know we have a progressive disease and we really want some objective feedback on how our condition is different from say a year ago. What symptoms are worse, what’s better, what’s the same?

Double Hit

The discovery in 1982 that a badly synthesized street drug could induce Parkinsonism in young California addicts (the so-called Frozen Addicts) led to the identification of a new neurotoxin, MPTP.

Hedgehogs Wanted

Philosopher Isaiah Berlin argued that great thinkers come in two varieties: foxes and hedgehogs. Foxes dabble, often brilliantly, in many things; hedgehogs discover and develop one big defining idea.

Profile: Tom Isaacs

In 1996, a 27-year-old London-based surveyor called Tom Isaacs was diagnosed with Parkinson's disease. Like others before him, he struggled to come to terms with his new identity. As he put it, “The truth was that I was now trapped inside a body that was now ageing at an alarming rate and was often incapable of responding to the demands put on it.”

The Patient Perspective: Joel Havemann

Every Parkinson’s patient is curious about what the future holds. One way to anticipate what’s coming is to learn from parkies further along in their disease. Unfortunately, it turns out that while many patient memoirs chronicle the early years of PD, there are very few accounts that document the long-term trajectory of the condition. An exception is Joel Havemann’s smart book, A Life Shaken.

8 October 2013

New Study Links Depression in Newly Diagnosed Parkinson’s Disease Patients to Reduced Striatal Dopamine Synthesis

According to the Parkinson’s Disease Foundation, up to 60% of individuals with Parkinson’s disease (PD) exhibit mild to moderate depression, which is often underdiagnosed. It is unclear whether depression results from having a debilitating disease or reflects a parallel abnormal change in the brain caused by PD pathophysiology.

Letter From Montreal

The opening ceremony was intensely moving. United by a common enemy, over three thousand PD patients, caregivers, researchers and clinicians from 60 countries assembled in Montreal’s Palais des congrès. The audience was animated, frequently rising to give standing ovations for the inspiring speakers who urged them not to give up hope.

Turning Failure into Success?

Every year, the NIH spends some $30 billion on biomedical research. The private sector – including the medical device industry, big pharma and the biotech sector –  chips in another $70 billion. What do we get for this investment? According to comedian Chris Rock, we don’t get many cures.

Interview: Caroline Tanner

Caroline (Carlie) Tanner had always planned to specialize in family medicine. But while a medical student in Chicago, she fell under the spell of neurologist Harold Klawans. Klawans – one of the first neurologist to use levodopa therapy with PD patients – convinced the young doctor that Parkinson’s was an exciting area of research and practice. Says Tanner, “The idea of being able to intervene with a transformative therapy like levodopa was very attractive, so after some soul-searching, I switched my concentration from family medicine to neurology.”

The L-dopa Conundrum

Few episodes in medical history are as dramatic as the “discovery” back in the 1960’s of L-dopa therapy. University of Rochester Medical Center’s Karl Kieburtz, an authority on the history of the drug, describes L-dopa as “one of the most potent therapies in all of neurology– indeed in all of medicine – think about it: to take someone who was essentially rigid like a stone…and enable them to get up and walk and function…it’s unbelievable.”

Now For The Bad News

The Holy Grail of PD research is to find a disease-modifying therapy. If one could deliver neurotrophic factors to the putamen, for example, and rescue ailing dopamine neurons, it might change the trajectory of the disease. Unfortunately, most recent efforts have ended in failure.

Brain Strains

Sometimes good proteins go bad. They change their shapes – from a soluble alpha helical conformation to an insoluble beta sheet one – stick to other proteins, and form fibrils that grow into clumps. Along the way cells die.

Interview: Roger Barker

Roger Barker says that he was inspired to become a clinician researcher after meeting the great neuroscientist David Marsden. As Barker puts it, “the minute I met David Marsden I wanted to be David Marsden, a person equally at home in the clinic and the laboratory”. When I visited the 51-year-old Parkinson’s and Huntington’s researcher during a recent visit to the UK, he seemed to be well on his way to accomplishing that goal.

6 June 2013

PD-Like Sleep and Motor Problems Observed in α-Synuclein Mutant Mice

The presence of Lewy bodies in nerve cells, formed by intracellular deposits of the protein α-synuclein, is a characteristic pathologic feature of Parkinson’s Disease (PD). In the quest for an animal model of PD that mimics motor and non-motor symptoms of human PD, scientists have developed strains of mice that overexpress α-synuclein. By studying a strain of mice bred to overexpress α-synuclein via the Thy-1 promoter, scientists have found these mice develop many of the age-related progressive motor symptoms of PD and demonstrate changes in sleep and anxiety. Their results are published in the latest issue of Journal of Parkinson’s Disease.

Pisa Therapy, Targeting alpha-synuclein & A Change of Purpose

Pisa syndrome is a rare complication of PD, where the trunk tilts to one side, causing postural instability. Shih et al present a case study of a 62-year-old-woman with right-sided lean, who fell frequently. The team treated her with DBS surgery to her left pedunculopontine nucleus (PPN). A striking video documents the patient’s slow but steady improvement.

Profile: J. William Langston

Meet Bill Langston, a giant of neuroscience. A major researcher who’s co-authored some 360 peer-reviewed articles. The winner of numerous awards, including the Sarah M. Poiley Award from the New York Academy of Sciences, the James Parkinson 30th Anniversary Award from the Parkinson’s Disease Foundation, and the Movement Disorders Research Award from the American Academy of Neurology.

Ceregene, Alpha-synuclein, Heart Failure & DBS

More bad news for neurotrophic factors—the appealing theory that growth factors (e.g. glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF) and neurturin (NRTN)) might rescue weakened neurons and halt PD. First, there was Amgen’s failed direct GDNF infusion trials. Then, in February British company Phytopharm plc announced that Cogane, an oral medicine designed to stimulate production of GDNF and BDNF, showed no efficacy in a phase II trial on early stage PD patients.

Profile: Patrik Brundin

Swedish neuroscientist Patrik Brundin keeps a picture of his father on his office wall as a reminder of why he became a Parkinson’s disease researcher. In 1974, when the Brundin family lived in Darlington, in the north of England, a local neurologist Dr Saunders diagnosed Patrik’s father, Bertil, with Parkinson's disease. Bertil Brundin –-an executive for a Swedish lawnmower company called Flymo–- was put on the just released medication, L-dopa. Patrik remembers his mother asking the neurologist “would it arrest the disease”? To which Dr.

Profile: Bastiaan Bloem

In the dramatic open to his 2011 TED talk, “From God to Guide,” neurologist Bastiaan “Bas” Bloem is lifted high above the stage by a crane to the sound of celestial music. Far below, a patient asks him for help. Bloem tersely tells the patient he has Parkinson’s disease and orders him to take carbidopa/levodopa three times a day. But the patient is not satisfied and complains in desperation, “Doctor you must take me seriously”.

Decoding Alpha-Synuclein: more baby steps

In 1997, scientists reported finding a genetic mutation for a common brain protein called alpha-synuclein in affected members of the Contursi kindred—an Italian-American family with a rare inherited form of PD. This protein was subsequently found to be a major component of Lewy bodies and Lewy neurites—the pathological hallmarks of regular idiopathic PD.

Still grafting after all these years

In November 1987, Lund scientists grafted fetal neurons into the brain of a 47-year old PD patient, launching an era of neural grafting. After some promising initial results, two negative US double blind sham surgery trials (in 2001 and 2003) brought the field to a virtual standstill. In a thoughtful look back at the past 25 years, some of the original pioneers review some lessons learned (Lancet Neurology).

Pill of Pills, Early Stimulation & Failure to Grow

PD patients can’t live without levodopa. Living with it is no picnic either. The drug’s short half-life (1.5-2 hours) and Parkinson’s relentless disease progression make a volatile combination.

The Roots of Compulsion, Diagnostic Markers & Java Science

Surveys have found that up to 14% of PD patients treated with dopamine agonist medication exhibit signs of compulsive gambling, shopping, eating, and sexual behavior. In the January 8, 2013 edition of Neurology, Daniel Weintraub et al looked to see if recently diagnosed untreated PD patients displayed similar signs of so-called impulse control disorders (ICDs), when compared to healthy controls.

Positive News About ProSavin: But Don’t Get Too Excited!

By the time people are diagnosed with Parkinson’s disease, they have lost a sizable fraction of their dopamine making cells in the substantia nigra pars compacta region of the brain, together with the vital axonal projections that deliver dopamine to the striatum.

1 July 2012

Years before Diagnosis, Quality of Life Declines for Parkinson’s Disease Patients

Growing evidence suggests that Parkinson’s disease (PD) often starts with non-motor symptoms that precede diagnosis by several years. In the first study to examine patterns in the quality of life of Parkinson’ disease patients prior to diagnosis, researchers have documented declines in physical and mental health, pain, and emotional health beginning several years before the onset of the disease and continuing thereafter. Their results are reported in the latest issue of Journal of Parkinson’s Disease.

19 June 2012

Sleep Improves Functioning in Parkinson’s Patients, but Reasons Remain Elusive

Some Parkinson’s patients report that their motor function is better upon awakening in the morning, which is contrary to what would be expected after a night without medication. This phenomenon, known as sleep benefit, has been studied but no consistent variables have been found and in the last decade there has been little new research. A new study, published in the June issue of the Journal of Parkinson’s Disease, assesses a large sample of Parkinson’s disease (PD) patients and confirms that some patients experience sleep benefit, both overnight and following afternoon naps, but finds no significant variables between those who do benefit and those who do not.

23 April 2012

19th Century Therapy for Parkinson’s Disease May Help Patients Today

In the 19th century, the celebrated neurologist, Jean-Martin Charcot, developed a “vibration chair” to relieve symptoms of Parkinson’s disease. He reported improvements in his patients, but he died shortly thereafter and a more complete evaluation of the therapy was never conducted. Now a group of scientists at Rush University Medical Center have replicated his work, and they report that while vibration therapy does significantly improve some symptoms of Parkinson’s disease, the effect is due to placebo or other nonspecific factors, and not the vibration. Their study is published in the April issue of Journal of Parkinson’s Disease.

17 April 2012

New Findings and Imaging Techniques May Aid Diagnosis of Concomitant Alzheimer’s in Patients with Parkinson’s Disease Dementia

Dementia is a frequent complication of Parkinson’s disease (PD), but it is clinically impossible to distinguish PD dementia (PDD), which develops from the progression of the Lewy body pathology that underlies PD, from PD with coexistent Alzheimer’s disease (PDAD). Both have similar characteristics. A team of scientists has found that PDAD patients have much denser accumulations of amyloid plaques in the striatal area of the brain than PDD patients. The results suggest that recently developed imaging techniques may be able to identify striatal amyloid plaques in the living brain and could be useful for distinguishing PDD from PDAD. Their results are published in the April issue of the Journal of Parkinson’s Disease.

24 January 2012

Scientists Report First Step in Strategy for Cell Replacement Therapy in Parkinson’s Disease

Induced pluripotent stem cells (iPSC) are a promising avenue for cell replacement therapy in neurologic diseases. For example, mouse and human iPSCs have been used to generate dopaminergic (DA) neurons that improve symptoms in rat Parkinson’s disease models. Reporting in the current issue of the Journal of Parkinson’s Disease, a group of scientists from Japan evaluated the growth, differentiation, and function of human-derived iPSC-derived neural progenitor cells (NPCs) in a primate model, elucidating their therapeutic potential.

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