Joohi Jimenez-Shahed, MD Assistant Professor of Neurology Baylor College of Medicine 8 th Annual IMHO Convention April 30, 2011 – Houston, TX Parkinson’s disease

April is Parkinson’s Awareness Month The tulip was first recognized as a symbol for Parkinson’s in At that time, a Dutch horticulturalist named J.W.S.Van der Wereld decided to honor Dr. James Parkinson, the first person to describe Parkinson’s in 1817, by naming a tulip after him. It thus became a symbol for Parkinson’s disease. James Parkinson 1817: Essay on the Shaking Palsy

What is Parkinson’s disease? Parkinson’s disease (PD) is a chronic and progressive movement disorder that involves the malfunction and death of vital nerve cells in the brain, called neurons. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As Parkinson’s progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.

What is PD? PD is a neurodegenerative brain condition  2 nd most common after Alzheimer’s The major PD symptoms are caused by loss of cells in the brain that produce dopamine Up to 70% of dopamine-producing cells in the substantia nigra are lost by the time symptoms first appear.

Cardinal Motor Symptoms of PD Resting tremor Bradykinesia Rigidity Postural instability

Other Motor Features Loss of facial expression (“masked”, “poker face”) Speech: low volume, stuttering, echoing syllables Swallowing problems Drooling Stooped posture: bending at the neck and at the waist Dystonia: involuntary cramping or twisting of a muscle Small, illegible handwriting Vision: intermittent double vision

Non-motor symptoms in PD Mood Cognition (thinking/memory) Sleep Loss of bladder control* Constipation* Low or fluctuating blood pressure* Sweating* Sexual dysfunction* Pain Loss of smell and taste Impulse control disorders Fatigue / lack of energy Skin problems *symptom complex termed “dysautonomia”

Epidemiology of PD 7-10 million people worldwide live with Parkinson’s disease. In the U.S., as many as one million individuals live with PD  more than the combined number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig's disease. Approximately 60,000 Americans are diagnosed each year. Men are slightly more likely to have PD than women. Incidence of Parkinson’s increases with age  ~4% of people with PD are diagnosed before the age of 50.  Affects 1/100 people over the age of 60 Avg. patient with PD onset at 62 yrs will live approx. 20 yrs.

Genetic factorsEnvironmental factors Only about 10% of cases are truly genetic People with an affected 1st degree relative have a 2-3-fold increased risk of developing PD as compared to the general population Cannot test for all 13 genes that are known to be associated with PD Environmental factors linked with genetic susceptibility may underlie PD No specific toxin is the sole cause of the disease Rural living, well water, herbicide/pesticide use, MPTP are associated with increased risk Caffeine, smoking associated with decreased risk What causes PD? PD probably represents a group of disorders resulting in a final common pathway

Dopamine Dopamine is a neurotransmitter responsible for cell to cell signaling in the brainstem and deep brain structures Dopaminergic cells influence the speed, regularity, coordination, and control of movement. Complex interactions between these brain structures allow us to control and fine tune all movements that we make.

Dopamine Dopamine-producing cells also connect to other non- movement brain areas, and can influence mood, reward seeking, motivation PD is more than a “shaking palsy”

Diagnosis of PD No diagnostic test for idiopathic Parkinson’s disease. Diagnosis rests on history and neurological examination. Blood tests and scans are ordered to check for other conditions that could cause parkinsonism. GE’s DaTscan™: First and only FDA-approved visual adjunct imaging agent to aid in differentiation between essential tremor and parkinsonian syndromes (does not diagnose PD)

Natural Progression of PD with No Treatment National Parkinson Foundation Web site. PreclinicalSymptomatic Diagnosis Dopamine neurons Motor ratings Time Threshold for some non-motor symptoms Threshold for motor signs and symptoms Symptoms may not require medication for several years post diagnosis Patients may have 1 year between appearance of motor symptoms and diagnosis (up to 70% lost by the time symptoms appear)

PD Treatment: General Principles No therapy is curative Treatment is directed at maintaining functional independence Levodopa therapy is the “gold standard”  First described to improve parkinsonian symptoms in the 1960s  “Awakenings” There is no single correct way to treat PD; individualize therapy for each patient

Treatment goals in PD Symptom control  Maintain functional independence: work, hobbies, leisure activities  Maintain quality of life  Improve social functioning (e.g., embarrassment by symptoms) Address non-motor features Minimize long-term complications Disease modification/Neuroprotection  No cure  No treatment clearly slows the progression of disease  Major focus of research and many new therapies – invasive or otherwise

Treatment options Dopamine-related treatments Non-dopamine, symptom- related treatments Replace dopamine  levodopa Stimulate dopamine receptors  dopamine agonists Prevent dopamine from breaking down  MAO-inhibitors  COMT inhibitors Just for tremor  anticholinergics Just for dyskinesia  amantadine Muscle relaxers Medicines for non-motor features

Disease progression EarlyModerateAdvanced Mild symptoms Still independent “Honeymoon period” Meds control symptoms Motor complications: freezing, falls Symptoms less easily controlled with medications Disability and dependence on others Cognitive decline Moderate stage - I Motor fluctuations (on/off) are mild Symptoms begin to affect daily functions Additional medications needed Moderate stage - II More obvious motor fluctuations (on/off) Dyskinesias Levodopa and adjunct treatments Symptoms get worse over time Requires higher doses and addition of new drugs over time In advanced stages, patients may require 5-7 different drugs

Surgical therapies for PD Generally reserved for patients who have developed complications of therapy. Previous lesioning procedures (e.g., pallidotomy and thalamatomy) have been abandoned in favor of deep brain stimulation (DBS) due to side effects and loss of effect over time. DBS has been shown to significantly improve motor function and quality of life compared to continued best medical management

Can people die from Parkinson’s? Parkinson’s disease is a progressive disorder, but is not considered to be a fatal disease People with Parkinson’s experience a significantly decreased quality of life and are often unable to perform daily movement functions, such as getting out of bed unaided and driving. Most individuals are eventually forced to stop working due to the unavoidable progression of disabling symptoms. In some cases, people have died from Parkinson’s-related complications, such as pneumonia.

What is the cost of Parkinson’s? The combined direct and indirect cost of Parkinson’s disease, including treatment, social security payments and lost income from inability to work, is estimated to be nearly $25 billion per year in the United States alone. Medication costs for an individual person with Parkinson’s average $2,500 a year, and therapeutic surgery can cost up to $100,000 per individual.

Research Initiatives Basic sciences research directed at understanding the pathophysiologic mechanisms in PD  Generate targets for non-dopaminergic or neuroprotective therapies Parkinson’s Progression Markers Initiative (PPMI, MJFF)  5-year clinical study aiming to identify the earliest biomarkers of disease Define early diagnostic algorithms Identify biologic metrics of disease progression NIH Exploratory Trials in PD (NET-PD, NINDS)  5-yr study in 1720 patients to determine of creatine can slow the progression of PD Novel drug design and delivery Gene therapy – e.g., neurotrophic factors

Thank you! Questions?