Until recently, Parkinson’s disease was thought to affect only a small area of the brain, and primarily involved dopamine loss. Because other neurological diseases often mimic Parkinson’s, it is currently difficult to accurately and quickly diagnose. However, modern advances in neuropathology led to the discovery that Parkinson’s is a multi-system and complex disease that affects many areas of the brain, spinal cord, and peripheral autonomic nervous system. Knowing this enables clinicians to better diagnose patients by not only considering typical symptoms—such as tremor and slowness of movement—but looking at gastrointestinal, cardiac, and cognitive dysfunctions as well. Dr. J. William Langston, Chief Scientific Officer and founder of the Parkinson's Institute and Clinical Center (PI), is revolutionizing Parkinson’s disease research through his innovative discoveries over the past 26 years. Working with his colleagues at the Parkinson’s Institute he is exploring the causes of Parkinson’s disease through novel transgenic animal models, developing ways to identify the disease during the early pre-motor stage, and designing new strategies and therapies that broadly target all areas affected by the disease in order to slow or halt its progression. 

A cutting-edge powerhouse driving current and future research in Parkinson’s disease, the Institute’s highly translational model includes a basic and clinical research program and a day-to-day clinic with patient care. He founded the institute after discovering an agent induced by a synthetic heroin, causing young patients to develop the disease overnight. This compound, MPTP, replicated all of the motor features of Parkinson's disease in humans. Dr. Langston used it to develop the first good experimental animal model for testing new drugs to treat Parkinson’s disease.

Dr. Langston works with the Institute’s team of researchers who specialize in genetics, biomarkers, stem cells, and the LRRK2 protein. They collaborate closely with clinical researchers, clinical trialists, and movement disorder specialists to develop ways to accurately diagnosis the disease early on. Based on their extensive results, they’ve also developed innovative pioneer clinical trials aimed at slowing or halting Parkinson's disease before it leads to impeding dysfunctions. They are currently building upon these models; their rapid advances in Parkinson’s disease research is largely inspired by the daily care of patients in their clinic.  

Current research areas include:

How Can Diagnostic Accuracy During the Pre-Motor Phase Improve? - Parkinson’s disease is much more diffused and pleomorphic than previously thought, presenting a significant problem with accurate diagnosis. The current diagnostic accuracy rate is at about 50% in early Parkinson’s disease, which can be hugely confounding for clinical trials for new drugs. Dr. Langston and his team are developing novel disease-modifying trials using cutting-edge imaging techniques that can improve diagnostic accuracy up to 90%. This has critical implications for clinical trials aimed at disease modification, as well as daily patient care in the clinic. The discovery of different variables involved in Parkinson’s disease provide critical clues on how to best identify this disease within the first five years. Because these non-motor features are unique to Parkinson’s disease compared to other neurodegenerative diseases, they provide a handle for a more accurate diagnosis. Additionally, many of these variables precede the onset of classic motor Parkinson’s disease (i.e. slowness of movement, rigidity, and tremor), enabling Dr. Langston and his team to develop ways to screen the general population and catch the disease before it advances and intervention becomes too difficult. They are using established diagnostic techniques that clearly image multiple aspects of Parkinson’s disease, distinguishing it from other neurodegenerative diseases. Their novel findings will redirect the development of therapies for use in future drug trials.  

How Do Brain and Cardiac System Assessments Lead to Accurate Diagnosis? - Parkinson’s disease causes an autonomic dysfunction in a patient’s peripheral autonomic nerves. Often, clinicians use an imaging tool—known as a DATSCAN—that shows the active dopamine depletion in the basal ganglia. However, there are many diseases that deplete dopamine, so this can result in an inaccurate diagnosis. Dr. Langston and his team are working with more sophisticated tests and imaging techniques that are sensitive to different variables and will enable doctors to diagnose patients in the early stage. He and his team are working on the hypothesis that Parkinson's disease uniquely causes peripheral autonomic neuropathy. This results in heart denervation, in which incoming fibers become damaged and a patient’s heart rate variability decreases significantly. Patients also commonly suffer a loss of smell. Using a quick EKG scan, a patient’s heart variability can be read within minutes, detecting potential cardiac denervation. Likewise, a simple smell test can reveal additional Parkinson’s disease symptoms. By coupling brain and cardiac scanning assessments in patients, early stage Parkinson’s disease can be more accurately diagnosed early on. Dr. Langston’s preliminary data suggests that these breakthrough assessments are crucial for drug modification trials. He aims to expand this work so it can be used more robustly and directly impact the lives of Parkinson’s disease patients.