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Research

The UCSF Parkinson's Disease Clinic and Research Center is committed to on-going research to improve treatment for Parkinson's disease. Our ultimate goal is to provide a definitive cure of this disease.

Information available on these topics:

Clinical Research

Overview:

Our clinical research efforts are pided between two broad types:

  1. Clinical trials of Experimental Therapy
    The first type seeks to test the effect of medications or surgical procedures (either established or experimental) on patients with PD. These studies are called clinical trials and are important in establishing the safety and defining the benefit of a particular therapy. Clinical trials often involve randomization (or unbiased assignment) into a given treatment or non-treatment (placebo) group. Subjects are selected on the basis of a number of factors including disease severity and current medications. Clinical trials may last from weeks to many months and may involve frequent contact with investigators.
  2. Fundamental Research
    The second type of research seeks to provide a new understanding of PD. This fundamental research may help identify new means of making a diagnosis of PD or may search to identify genes or environmental exposures (for example, foods or environmental toxins) that increase the risk of developing PD. Fundamental research often involves a single visit with an investigator. It often requires some specialized testing, such as providing a blood sample. For some of these studies, unaffected family members are asked to participate.

For information on current studies, please see Open Trials.

Faculty members in clinical research and their focuses:

Michael Aminoff, MD, DSc

Dr. Aminoff is interested in the physiological aspects of movement disorders. With collaborators, he is studying the cerebral accompaniments of the decision to make a movement in Parkinson’s disease and, in conjunction with personnel at the University of California Berkeley, the characteristics of the gait of parkinsonian patients.  Working with other investigators at UCSF, he is also investigating chemical biomarkers for Parkinson’s disease in the hope of identifying a disease biomarker that not only confirms the diagnosis but also provides information regarding disease progression.  Such a biomarker may be useful in developing medications to slow or halt the progression of PD.

Dr. Aminoff has also been involved in a number of clinical trials including, most recently, a gene therapy for Parkinson’s disease, and two other such studies are in the planning stage. He is a participant in a number of multicenter trials (as the principal investigator for the UCSF site), including a trial of a potential neuroprotective agents (NET-PD) funded by the federal government. With several colleagues, planning is also in process for translation of stem cell therapies to the clinical arena.

With other UCSF colleagues, Dr. Aminoff is involved in exploring the role of imaging techniques in distinguishing Parkinson’s disease from certain atypical parkinsonian syndromes.  He has also just established a protocol at UCSF for obtaining skin tissue from parkinsonian patients in order to generate induced pluripotential stem cells. These will be used as a platform to investigate potential new therapies for the disease.  

Chad Christine, MD

Dr. Christine has far ranging interests in Parkinson’s disease.  His research interests include: 1) developing a broader understanding of the causes of Parkinson’s disease (PD), 2) developing methods for earlier diagnosis of PD, and 3) developing improved treatment for PD.

Since 2001, he has been interested in identifying environmental exposures (including prescribe medications) that may increase the risk factor for PD.  Recognition of such exposures may allow prevention of future cases of PD.  He has also been involved in a study using specialized imaging techniques to differentiate PD from atypical parkinsonian disorders.  Identification of atypical disorders at an earlier stage may allow for more specific therapies that are under development to be tested at an earlier disease state.  Finally, in collaboration with other investigators at UCSF, Dr. Christine is investigating chemical biomarkers for PD.  The goal of this research is to identify disease biomarker that not only confirmed the diagnosis of PD but also provided information regarding disease progression.  It is hoped that such biomarkers would be useful in developing medications to slow or halt the progression of PD.

Dr. Christine’s research on Parkinson’s disease (PD) treatment has included participation in both medical and surgical treatment studies.  He has participated in numerous randomized treatment studies and has been an investigator Parkinson’s Disease Neuroprotection Clinical Trial (NET-PD) since 2006. He was a site investigator of a large study of antidepressants for PD. He also has collaborated in 2 randomized trials examining the relative benefits of globus pallidus versus subthalamic deep brain stimulation for the treatment of advanced Parkinson’s disease.  Finally, he was an investigator in a phase 1 study of gene therapy study for advanced Parkinson’s disease.  This study utilized the gene amino acid decarboxylase, the human gene which converts levodopa into dopamine.Because of promising results from this study, a phase 2 study is being planned. 

Basic Research

In addition to clinical research studies, our faculty investigates basic cellular mechanisms in PD.  This research focuses on dopaminergic neurons, neural toxicity, alpha-synuclein, mitochondria, and neurotransmitter release. 

Faculty members in basic research and their focuses:

Robert Edwards, MD

To understand the processes that cause Parkinson's disease, work in the laboratory of Robert Edwards, MD is addressing two fundamental aspects of the disorder. First, Parkinson's disease specifically affects dopamine neurons, and the selective vulnerability of these cells presumably reflects the intrinsic toxicity of their normal neurotransmitter, dopamine. Dopamine neurons must have mechanisms to protect against the toxicity of dopamine, and defects in these protective mechanisms may well give rise to Parkinson's disease. Over the last few years, the Edwards lab has identified key proteins that protect against dopamine and related toxicity. They are now using this information to develop animal models of the human disorder. In addition, Parkinson's disease appears to involve the development of protein deposits by dopamine neurons. A major component of these deposits is the protein alpha-synuclein, and mutations in alpha-synuclein can also cause rare familial forms of Parkinson's disease. Since the normal function of alpha-synuclein may impact on its ability to deposit and cause neural degeneration, the Edwards lab is also studying its function in the process of the neurotransmitter release.

For more information, please visit Dr. Edwards' laboratory website.

Ken Nakamura, MD, PhD

Parkinson's disease (PD) is a common and debilitating neurodegenerative disorder, resulting in substantial social and economic hardships. Current therapy is purely symptomatic and loses efficacy over time, as there is no known way to slow the underlying disease progression. Although it is not understood why cells degenerate in PD, multiple lines of evidence indicate that the PD protein alpha-synuclein and mitochondrial dysfunction play central roles in this process. 

In recent work, Dr. Nakamura's group used fluorescent synuclein probes to identify biologic membranes with which synuclein interacts. Using this approach, they found that synuclein preferentially binds to mitochondria versus other organelles. They then discovered that this interaction increases the rate of mitochondrial fission through a novel mechanism, resulting in a dramatic fragmentation of mitochondria. These changes compromise mitochondrial function over time, and predispose to neuronal death, revealing a potential mechanism by which synuclein may produce degeneration in PD.

Current studies in Dr. Nakamura's laboratory aim to better understand the biologic consequences of mitochondrial fragmentation by synuclein, and to elucidate potential therapeutic approaches to block this process. They are also actively investigating the effects of other PD proteins, parkin and PINK1, on mitochondrial biology in neurons. Their long term objectives are to advance the understanding of why PD occurs, and contribute to the development of new diagnostic and therapeutic approaches.

For more information, please visit Dr. Nakamura's laboratory website.

Krzysztof Bankiewicz, MD, PhD

Dr. Bankiewicz, throughout his career, has maintained a strong focus on the development of practical approaches to gene and cell replacement therapies.  He has displayed a remarkable ability to synthesize several individual technologies into powerful new approaches to the treatment of such serious disease as brain cancer and neurodegenerative disorders of the brain, including Parkinson's disease. Dr. Bankiewicz was instrumental at every stage of the Phase-1 clinical trial for AAV-hAADC gene therapy, now underway at UCSF, in resolving technical and scientific issues with respect to filing an IND application with the FDA, and also in recruiting a clinical team to undertake the clinical trial. 

For more information, please visit Dr. Bankiewicz's laboratory website.