Jon Palfreman’s Blog

Toward Personalized Medicine for Those with Parkinson’s

Neurologists often remark that Parkinson’s is a highly variable disease. Persons with Parkinson’s not only acquire the disease at different ages, they also manifest different clinical profiles, displaying symptoms that can progress at strikingly different rates. Read more.

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Book Review: Mentored by a Madman: The William Burroughs Experiment

Book: Mentored by a Madman: The William Burroughs Experiment
Author: Andrew Lees

A Drug that Melts in Your Mouth

For fifty years, L-dopa has been the gold standard for treating the symptoms of Parkinson’s disease. Much less has been written about another drug, apomorphine, a powerful dopamine agonist, which produces an L-dopa like response.  

The Next Big Thing for Monitoring Parkinson’s Disease

Neurologists typically monitor their Parkinson’s patients infrequently. Patients like me go in once every 6 months or so and do a test — the Unified Parkinson’s Disease Rating Scale or UPDRS. Every person with Parkinson’s knows this test, which takes about fifteen minutes.

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Deep Brain Stimulation: You Aint Seen Nothing Yet?

Since the FDA approved deep brain stimulation (DBS) for Parkinson’s disease in 2002, over 140,000 patients have undergone the procedure worldwide.

Focused Ultrasound

Before the advent of deep brain stimulation (DBS) some fifteen to twenty years ago, the only way neurosurgeons could mitigate Parkinsonian symptoms like tremor, rigidity, and dyskinesia, was by directly destroying pieces of brain regions such as the thalamus and globus pallidus internus.

Pricey Placebos

The placebo effect is a puzzling concept to get your head around. The idea that an essentially inert intervention — like a sugar pill, a saline injection, or a sham operation — can produce therapeutic benefit seems to defy common sense. But it’s very real.

Under My Skin

Many PD patients who take multiple carbidopa-levodopa pills orally every day experience sharp fluctuations in levodopa levels and suffer associated motor complications (e.g. intermittent "off" and "on" periods). Israeli-based NeuroDerm Ltd. has just reported encouraging news about its novel platform that seeks to minimize this problem by delivering liquid carbidopa-levodopa continuously over 24 hours.

Optimal Care

The current issue of the Journal of Parkinson’s Disease includes a new feature, “How I examine my patient”, a section designed to help improve the clinical skills of physicians, allied health professionals, and other professionals involved in the care of patien

Letter from Stockholm: Disruption Ahead!

One of the most interesting events at the 18th International Congress of Parkinson’s Disease and Movement Disorders in Stockholm was a dinner hosted by the Kinetics Foundation.

Letter from Stockholm: Learning From Our Failures

The hunt for so-called disease-modifying interventions for Parkinson’s disease has not been going well of late. In Stockholm this week at the 18th International Congress of Parkinson’s Disease and Movement Disorders, some of the world’s leading researchers gave their differing analyses of what lessons should be learned from the set backs.

Letter from Stockholm: Dopamine: Carlsson’s Remarkable Chemical

The first speaker at the 18th International Congress of Parkinson’s Disease and Movement Disorders in Stockholm was Swedish Nobel laureate Arvid Carlsson. Carlsson, now in his 90s, eloquently told the story of his groundbreaking research in the 1950s that led to the dopamine theory of Parkinson’s disease. Carlsson recounted how he used the anti-psychotic medication reserpine to paralyze rabbits and how he then unfroze the animals with dopa.

IOS Press publishes a new edition of The Case of the Frozen Addicts

In 1985, I produced a documentary for the PBS series NOVA, entitled “The Case of the Frozen Addicts”. The film told the story of six young California drug abusers mysteriously struck with the symptoms of Parkinson’s disease, a neurodegenerative condition that normally affects the elderly. Bill Langston, then an unknown clinician at the San Jose Valley Medical Center, discovered the unlucky individuals languishing in psych wards and jail cells and had temporarily reversed their symptoms with the drug L-dopa.

Glimmers of Hope

In November 1987, Lund neuroscientists grafted fetal dopamine neurons into the brain of a 47-year old PD patient, launching a hopeful new era of neural grafting aimed at reversing the symptoms of PD.

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.

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?

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.

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.

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.

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.

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.

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.