Jon Palfreman’s Blog

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

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.

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.

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.

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.

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.

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.

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?

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.

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.”

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.

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.

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).

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.