New Clinic Treats Gastrointestinal Manifestations of Parkinson’s Disease
While Obtaining Clues About the Disease’s Pathogenesis
This specialized clinic sees patients with gastrointestinal complications of Parkisnon's disease. They will also discuss motility testing and refer you for the appropriate study if necessary.
Call the clinic at 310-208-5400.
At a newly opened clinic within the integrated UCLA Health system for treating the GI symptoms of patients with Parkinson’s disease, two clinician-scientist members of the UCLA Vatche & Tamar Manoukian Division of Digestive Diseases faculty are gleaning important clues about the early manifestations of the neurodegenerative disease at the same time that they are applying their expertise as gastroenterologists to improve patients’ quality of life.
It is well established that gastrointestinal motor function can be negatively altered by Parkinson’s disease, and an emerging body of research indicates that the disease may start in the gastrointestinal tract before later spreading to the brain. But the GI tract’s role in the pathogenesis of Parkinson’s disease, and the mechanisms by which Parkinson’s disease alters gastrointestinal motor function, are not yet fully described.
Wael El-Nachef, MD, PhD, and Elizabeth Videlock, MD, PhD, assistant clinical professors in the division, note that most patients with Parkinson’s disease experience GI symptoms such as constipation and bloating, and that in many cases these symptoms precede the diagnosis of Parkinson’s by several years. “This has long been known, yet the reasons weren’t well understood,” Dr. El-Nachef says. “But there is growing evidence to suggest that the same process involved in the central nervous system is also involved in the enteric nervous system, through the aggregation of the alpha synuclein protein to form Lewy bodies. And some studies indicate that the enteric nervous system is involved first.”
There is considerable interest in examining this potential pathogenesis for multiple reasons, Drs. El-Nachef and Videlock explain. The greater accessibility of the intestine vs. the brain could facilitate obtaining biopsy samples in patients at risk for Parkinson’s disease, enabling earlier identification of the disease and potentially leading to the development of drugs to prevent its progression to the brain.
“Parkinson’s disease progresses slowly, and by the time symptoms occur, it’s usually at the end of the pathologic process,” Dr. Videlock says. “Currently we can diagnose patients only once the neurons have died, but if we could identify patients earlier, we might be able to prevent the neurons from dying and the symptoms we think of as Parkinson’s disease from developing. We also know from population studies that constipation is a risk factor, and from talking to Parkinson’s disease patients, many notice that those symptoms started as long as 10 years prior to their diagnosis. If we can identify that early process, it could lead to more effective therapy.”
In the new clinic for Parkinson’s patients with GI issues, Drs. Videlock and El-Nachef, along with Jeffrey L. Conklin, MD, medical director of the UCLA Robert G. Kardashian Center for Esophageal Health and UCLA GI Motility Program, see patients with symptoms that include bloating and difficulty swallowing, as well as nutritional deficiencies. But the vast majority are experiencing unresolved constipation. “Symptoms such as constipation are difficult to treat in this population,” Dr. Videlock says. “Our expertise as gastroenterologists is particularly important because we have more familiarity with the different constipation treatments, and we’re also learning what works best in this population.”
Adds Dr. El-Nachef: “Many of these patients don’t fit the textbook description of the symptom they’re experiencing, and so you really have to think outside the box. That’s where our focus on neuro-gastroenterology can be quite helpful.” The physicians at the Parkinson’s GI clinic work in close consultation with leading neurologists at UCLA, including Jeff Bronstein, MD, PhD, director of the UCLA Movement Disorders Program, in ensuring that the medications they prescribe for GI symptoms are optimal in the context of the patient’s disease and the other drugs they are taking.
Dr. Videlock notes that improving patients’ gut function is important not just for the quality-of-life benefits that come from alleviating their GI symptoms. “We know that addressing gut symptoms improves the efficacy of the Parkinson’s medications,” she says. “If you have slow gut motor function, with delays in the emptying of your stomach, you don’t get the full effect of the medicine. Studies have shown that the bacterial overgrowth that can occur if the gut moves too slowly can metabolize the medication. So by improving GI symptoms, we can also improve Parkinson’s symptoms.”
In the lab, Dr. El-Nachef is working with Dr. Bronstein to study the involvement of the intestinal nervous system in a zebrafish model of Parkinson’s disease. “One of our goals in this research is to assess whether we see a loss of neurons in the intestine, what the timing of that is, and how it tracks with the development of motor symptoms in this model,” Dr. El-Nachef says.
Dr. Videlock’s laboratory research, in collaboration with Ming Guo, MD, PhD, a professor of neurology and molecular & medical pharmacology, examines the role of intestinal inflammation in the development of Parkinson’s disease in mouse and human cellular models. “At UCLA we have research covering all of the integrated components of the gut in Parkinson’s disease, including the nerves, the gut microbiome and, in my case, the lining of the gut and the integrity of the barrier,” Dr. Videlock notes. “Parkinson’s patients have increased levels of cytokines, which are a sign of inflammation. And in some animal studies, gut inflammation can be a trigger for genetic forms of the disease.”
In the clinic, Drs. Videlock and El-Nachef are obtaining important insights about the history of their patients’ symptoms that is helping to inform their research. “We would like to know more about the characteristics of constipation onset that might point to the possibility that a patient is at risk for developing Parkinson’s disease,” Dr. Videlock says. “What are the clues that this might be different from the normal variant of constipation? Does it usually happen suddenly or gradually? Is there a symptom cluster that might be indicative?”
At the same time, they are using systematic diagnostic and therapeutic approaches to improve patients’ quality of life. The clinic’s providers work closely with Dr. Bronstein to explore relationships between the neurological and gastrointestinal aspects of the disease. Dedicated GI dietitians work to improve the patients’ nutritional state, and UCLA speech pathologists diagnose the swallowing problems associated with Parkinson’s disease.
“We’re able to bring a different perspective to these patients and the treatment of their GI manifestations,” Dr. El-Nachef says. “And we believe that having this cohort of patients in our clinic will facilitate new clinical and translational research projects that will help bring the work we are doing in the laboratory to fruition.”