Parkinson's Disease Archives - Sanford Burnham Prebys

Tag: Parkinson’s Disease

Institute News

A year in review: Our top 10 discoveries of 2019

AuthorMonica May
Date

December 4, 2019

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At Sanford Burnham Prebys, we uncover the origins of disease and launch bold new strategies that lay the foundation for achieving cures. This year our scientists made significant progress—revealing new insights into how we treat some of the deadliest cancers, address neurological disorders such as Parkinson’s and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and more.

Read on to learn more about our top 10 discoveries of the year. To receive more frequent updates on our discoveries, subscribe to our monthly newsletter at the bottom of this page.

  1. One-two punch drug combination offers hope for pancreatic cancer therapy. Ze’ev Ronai, PhD, identified a combination of two anti-cancer compounds that shrank pancreatic tumors in mice—supporting the immediate evaluation of the drugs in a clinical trial. The study was published in Nature Cell Biology.
  2. Targeted treatment shrinks deadly pediatric brain tumors. Robert Wechsler-Reya, PhD, reported that a targeted therapy that blocks a protein called LSD1 shrank tumors in mice with a form of pediatric brain cancer known as medulloblastoma. LSD1 inhibitors are currently under evaluation in clinical trials for other cancers, which could speed their potential path to children. The study was published in Nature Communications.
  3. Epigenetic change causes fruit fly babies to inherit diet-induced heart disease. Rolf Bodmer, PhD, showed that reversing an epigenetic modification or over-expressing two genes protected fruit fly children and grandchildren from the negative heart effects of their parents’ fatty diet. These findings help explain how obesity-related heart failure is inherited and uncover potential targets for treatment. The study was published in Nature Communications.
  4. Amyotrophic lateral sclerosis (ALS) research reveals new treatment approach. Huaxi Xu, PhD, extended the survival of mice with ALS-like symptoms by elevating levels of a protein called membralin using a gene therapy approach. The study was published in the Journal of Clinical Investigations.
  5. How prostate cancer becomes treatment resistant. Jorge Moscat, PhD, and Maria Diaz-Meco, PhD, identified how prostate cancer transforms into an aggressive, treatment-resistant subtype called neuroendocrine prostate cancer (NEPC) following treatment with anti-androgen therapy. Their findings uncover new therapeutic avenues that could prevent this transformation from occurring and reveal that an FDA-approved drug holds promise as an NEPC treatment. The study was published in Cancer Cell.
  6. Boosting muscle stem cells to treat muscular dystrophy and aging muscles. Alessandra Sacco, PhD, uncovered a molecular signaling pathway that regulates how muscle stem cells decide whether to self-renew or differentiate—an insight that could lead to muscle-boosting therapeutics for muscular dystrophies or age-related muscle decline. The study was published in Nature Communications.
  7. Functional hair follicles grown from stem cells. Alexey Terskikh, PhD, created natural-looking hair that grows through the skin using human induced pluripotent stem cells (iPSCs), a major scientific achievement that could revolutionize the hair growth industry. Stemson Therapeutics has licensed the technology.
  8. Potential targeted treatment for acute myeloid leukemia identified. Ani Deshpande, PhD, showed that a protein called BMI1 is a promising drug target for an AML subtype in which two normally separate genes fuse together. The findings, published in Experimental Hematology, provide a rationale for evaluating a BMl1-inhibiting drug that is currently in clinical development as a potential treatment for this subtype.
  9. Antimicrobial protein implicated in Parkinson’s disease. An immune system protein that usually protects the body from pathogens is abnormally produced in the brain during Parkinson’s disease, Wanda Reynolds, PhD, reported in Free Radical Biology & Medicine. The discovery indicates that developing a drug that blocks this protein, called myeloperoxidase (MPO), may help people with Parkinson’s disease.
  10. Digestion-aiding herbs alter gut microbiome. Scott Peterson, PhD, found that four herbs—turmeric, ginger, long pepper and black pepper—promoted strong shifts in the gut bacteria that are known to regulate metabolism, providing insights that could help us protect our health. The study was published in Evidence-Based Complementary and Alternative Medicine.
Institute News

Antimicrobial protein implicated in Parkinson’s disease

AuthorMonica May
Date

July 17, 2019

Myeloperoxidase enzyme

An immune system protein that usually protects the body from pathogens is abnormally produced in the brain during Parkinson’s disease, scientists from Sanford Burnham Prebys report. The discovery, published in Free Radical Biology & Medicine, indicates that developing a drug that blocks this protein, called myeloperoxidase (MPO), may help people with Parkinson’s disease.

“Prior to this study we knew that MPO was a powerful oxidizing enzyme found in white blood cells used to protect us from microbial infections,” says Wanda Reynolds, PhD, senior author of the study and adjunct associate professor at Sanford Burnham Prebys. “This is the first time that scientists have found that MPO is produced by neurons in the Parkinson’s disease brain, which opens important new directions for drug development.

Parkinson’s disease occurs when the neurons that control movement are impaired or destroyed. Over time, people with the disease lose mobility. The disorder affects men more than women; most people develop the disease around age 60. Currently available medicines address the disease’s symptoms, not the root cause. There is no cure.

“For this research we compared brain samples from people who had succumbed to Parkinson’s disease to those from normally aged brains,” says Reynolds. “We found that MPO was only expressed in neurons in people who succumbed to Parkinson’s disease—and not the healthy samples. 

“We then created unique mice that modeled Parkinson’s disease and expressed MPO. These mice accumulated toxic, misfolded proteins in the brain. Additionally, the MPO produced in the brain had an altered shape. As a result, instead of being stored inside neurons, MPO is capable of being ejected from the cell and cause further brain damage. We also found that MPO was located preferentially in the memory-associated regions of the brain—the cortex and hippocampus—indicating it plays a role in memory disruption.” 

Reynolds and her team are already working to develop an MPO inhibitor, which they hope will slow the progression of Parkinson’s disease. Based on Reynold’s previous research showing that MPO is abnormally expressed in the Alzheimer’s disease brain, an MPO inhibitor may also hold potential as an Alzheimer’s disease treatment. 

The first author of the study is Richard A. Maki, PhD, of Sanford Burnham Prebys. Additional authors include Michael Holzer, PhD, Gunther Marsche, PhD, and Ernst Malle, PhD, of the Medical University of Graz; Khatereh Motamedchaboki of Sanford Burnham Prebys; and Eliezer Masliah, MD, of the National Institutes of Health (NIH) and University of California, San Diego.

This work was supported by the NIH (ROINS074303, ROIAG017879, and ROI AG040623) and the Austrian National Bank (17600). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Institute News

Parkinson’s research benefits from powerful collaboration

AuthorDeborah Robison
Date

June 19, 2017

Mayo Clinic Collaboration

Medical discoveries may languish in laboratories for years without the necessary tools and means to drive findings further toward the development of novel therapeutics. This could have been the case for Dr. Pamela McLean, a Parkinson’s disease expert at the Mayo Clinic in Jacksonville, Fla., had a collaboration with SBP’s drug discovery team in Lake Nona not emerged.

McLean’s deep clinical experience and unique insights into the molecular basis of the disease, combined with SBP’s screening technology and drug discovery expertise, produced promising findings and attracted a significant grant from The Michael J. Fox Foundation (MJFF). Just recently, the researchers were awarded a special MJFF bridge grant to ensure that the science continues to move forward.

McLean studies the role of alpha-synuclein, a protein that misfolds and aggregates in the brain regions that are critically involved in Parkinson’s disease. She brought her cell-based models of alpha-synuclein protein “clumping” to SBP where the drug discovery team screened through 800,000 chemical compounds for substances that were capable of removing the abnormal protein and protecting the cells. Results from the initial study identified eight compounds as potential inhibitors of alpha-synuclein aggregation.

“Our current investigation will enhance the effectiveness of the drug candidates that we previously identified and advance them to pre-clinical development on the road to patient treatment,” said Dr. Layton Smith, director of SBP at Lake Nona Drug Discovery.

During this phase, chemistry teams will validate and refine the drug candidates’ biological activities. The process will likely eliminate some candidates in a testing funnel designed to narrow the compounds to those that exhibit the desired properties, such as inhibiting protein aggregation in the brain. Concurrently, McLean will explore the drug candidates’ mechanism of action to understand if the compounds work by blocking aggregation, enhancing removal of the clumps or by some other means. New therapies are critically needed to treat the more than 1 million Americans afflicted with Parkinson’s disease. Current medicines treat symptoms but do not reverse the effects of the disease.