Center for Neurologic Diseases Archives - Sanford Burnham Prebys
Institute News

Evan Snyder named Fellow of the Child Neurology Society

AuthorScott LaFee
Date

May 28, 2025

Evan Snyder, MD, PhD, professor in the Center for Neurologic Diseases, has been named a Fellow of the Child Neurology Society, honoring a distinguished career and significant contributions in the field of child neurology.

Snyder, who is also a member of the Cancer Genome and Epigenetics Program at Sanford Burnham Prebys, is a longtime leader in pediatric neuroscience and stem cell research. He joined Sanford Burnham Prebys in 2003, and was founding director of its original Stem Cell Research Center.

The Child Neurology Society is a professional organization whose mission is to promote the optimal care of children with neurological and developmental disorders by providing education, advocacy and support for clinicians and researchers in the field.

Snyder was cited for his clinical expertise, research contributions and ongoing commitment to the mission of the Society. He is featured in the second edition of Child Neurology: Its Origins, Founders, Growth and Evolution, a collection of biographies detailing the lives of innovators in child neurology throughout history.

Institute News

Yasuyuki Kihara wins a dream award

AuthorMiles Martin
Date

November 9, 2022

And he’s had his eye on it for more than a decade.

Research Assistant Professor Yasuyuki Kihara, PhD, has won an Eicosanoid Research Foundation (ERF) Young Investigator Award, which is presented every other year to three early-career faculty researchers who have made breakthroughs in the field of bioactive lipids.

The award may not come with a cash prize, but for Kihara, this prize is priceless. 

“The first time I applied for this award was around 2009, and I’ve applied several times since then,” he says. “This has been many years in the making, and I’m incredibly honored to receive this award.”

Kihara is the first Sanford Burnham Prebys scientist to win this award for research completed at the Institute. Assistant Professor Victoria Blaho, PhD, also received the award in 2007, before becoming a Sanford Burnham Prebys faculty member in 2019. 

Applying bioactive lipids to multiple sclerosis: Kihara’s prize-winning research

Kihara has devoted his scientific career of more than 20 years to studying bioactive lipids, a broad group of molecules that cells use to communicate and to control their activities. Some of the most well-known examples of bioactive lipids are the hormones testosterone and estrogen, but there are countless other examples in different parts of the body as well.

“Bioactive lipids are involved in signaling in every cell of every organism,” says Kihara. “Lipids are essential for life, and I’m not sure I could even imagine a biological process or a pathway that doesn’t involve a lipid at some step.”

Kihara’s work focuses on multiple sclerosis (MS), a potentially disabling disease of the brain and spinal cord that affects the brain’s ability to communicate with the rest of the body. MS occurs when protective structures in our neurons, called myelin sheaths, become damaged.

“Losing this myelin makes it much more difficult for the brain to send signals to other parts of the body,” says Kihara. “This causes a wide range of symptoms that can be debilitating for the people living with this disease.” 

In 2010, FDA-approved an oral drug for MS called fingolimod. Fingolimod has a chemical structure that resembles a bioactive lipid, and Kihara has teamed up with Professor Jerold Chun, MD, PhD, to study how this drug works at the molecular level to explore whether there may be other ways to leverage bioactive lipids against MS.

“We believe that cellular signaling pathways and the bioactive lipids that control them may have a more complicated role in MS than is currently understood,” says Kihara. “Studying these molecules at this fundamental level will help reveal new ways of treating the disease.”

Institute News

Jerold Chun receives a very special Alzheimer’s grant

AuthorMiles Martin
Date

May 13, 2022

Jerold Chun, MD, PhD, has been awarded a new grant for $250,000 from the Coins for Alzheimer’s Research Trust (CART) Fund, an initiative by Rotary International to encourage exploratory and developmental Alzheimer’s research projects. Chun’s two-year project will explore how virus-like elements in our DNA could play a role in the development of Alzheimer’s disease.

“We are so grateful for the support of CART and the Rotarians,” says Chun. “They’ve shown over the years that small contributions to Alzheimer’s research can add up to make a huge impact.”

Ancient viruses in our genome
Chun’s project will explore how Alzheimer’s disease relates to endogenous genes in our genome that are very similar to parts of modern viruses. This is because they originated from viruses that infected our ancient ancestors. Over millions of years of evolution, these viruses became a normal part of our genomic makeup. 

Chun and other researchers suspect that these viral-like genes may be able to form virus-like particles that move through connections among our brain cells. They hypothesize that this process could promote neurodegenerative diseases like Alzheimer’s. “This new grant from CART will help us figure out how these genes and particles work, which is a first step toward thinking about how we might leverage it for treatments.”

Funding research with spare change
CART began in the mid-1990s with an ambitious idea: Could collecting the pocket change of Rotary International members accumulate enough to support Alzheimer’s disease?

The idea was launched in 1996 at Rotary Clubs in South Carolina; and at every meeting, members were asked to donate their loose change to a fund for Alzheimer’s research. The idea exploded from there. Over time, individual clubs started donating portions of their fundraising proceeds, and donations even began to come in from non-Rotary members as CART’s reputation grew.

The fund has awarded more than $10 million in grants to more than 40 institutions since its inception. This year, one of those grants was awarded to Chun to explore a new direction for Alzheimer’s research. This is the first CART grant to be awarded to a Sanford Burnham Prebys researcher.

“Grants like this are important because they give scientists the resources to pursue brand-new research areas,” says Chun. “Every major scientific discovery starts somewhere, and this type of support gives us that starting place, for which we’re really grateful.”

Institute News

How Sanford Burnham Prebys is helping map the brain

AuthorMiles Martin
Date

October 11, 2021

By joining forces with hundreds of researchers across the country, a team from the Chun Lab at Sanford Burnham Prebys are working to create a comprehensive map of the human brain, in the hopes of leveraging that knowledge to better treat brain disorders.

Researchers in the lab of Sanford Burnham Prebys professor Jerold Chun, MD, PhD, have helped the NIH create a cellular atlas of the motor cortex – the area of the brain responsible for movement. Their work, published recently in the journal Nature, is the flagship paper for the NIH’s BRAIN initiative, a massive multi-institution project to unravel the mysteries of the human brain.

“There are hundreds of billions of cells in the brain, and identifying and classifying all the different types of brain cells is just too big a job for any single lab,” says Chun, who is a coauthor on the study. “Similar to efforts in particle physics, hundreds of neuroscientists have now come together and it’s really exciting for us to be part of this major effort.”

The NIH Brain Research through Advancing Innovative Neurotechnologies® (BRAIN) Initiative aims to revolutionize our understanding of the human brain to more effectively diagnose, treat and prevent neurological diseases and disorders. Since its launch in 2013, the BRAIN Initiative has awarded more than 900 grants to research institutions across the country, totaling $1.8 billion. 

Chun is one of the principal investigators of the BRAIN Initiative Cell Census Network (BICCN), a subset of the Initiative that aims to develop a database of all the brain cell types in humans, mice, and non-human primates.

“While the project is about exploring the brain, what we’re really interested in over the long term is the clinical applications,” says study coauthor Carter Palmer. “Understanding the nuances of the brain and how the trillions of neural connections really work is going to lead us to new targets for therapies and diagnostics so we can help people heal.” Palmer is a graduate student in Chun’s lab, alongside fellow co-authors Christine Liu and William Romanow.

There are over 150 billion cells in the average human brain and well over a thousand different cell types, depending on how you characterize them. With such a vast landscape to track, many different types of data are needed to develop a comprehensive atlas of the brain.

For their part, the Chun Lab provided single-cell transcriptomes for human brain cells, focusing on the motor cortex. Single cell transcriptomes provide a measure of how hundreds to thousands of genes are expressed in individual cells and can provide hints as to what functions those cells are serving. This process also provides a molecular definition of cell types, making it easier for researchers to identify and classify them.

“Looking at how genes are expressed gives us a wealth of information on what cells are doing, how they develop and how they’re interacting with other cells,” says Palmer. “And when our data feed into the data from other teams, we start to get a much clearer picture of what’s happening in the brain than has ever been possible.” 

Their flagship Nature paper is one of seventeen in a special edition of the journal, chronicling recent advances by hundreds of BICCN researchers. The team also contributed to a second paper in the issue, which expands on the first by comparing the motor cortex cells of humans, mice, and marmosets. These publications speak not only to the expertise of Chun and his colleagues, but to the power of collaborative, interdisciplinary work to achieve previously unheard-of research goals.

“Fifty years ago, a project like this would have been impossible, because we just didn’t have the technology or even basic knowledge to collaborate on such a large scale,” says Chun. “Huge initiatives like BRAIN are an important part of the future of scientific research, and we’re thrilled we were able to contribute to this milestone in neuroscience.” 

Institute News

New insights into Alzheimer’s disease

AuthorMonica May
Date

September 25, 2020

Sanford Burnham Prebys scientist publishes two papers that bring us one step closer to understanding—and potentially treating—the devastating condition.

For millions of families and caregivers around the world, the need for an effective treatment for Alzheimer’s disease remains urgent despite the ongoing pandemic. Now, two studies from Timothy Huang, PhD, who was recently promoted to assistant professor in the Degenerative Diseases Program at Sanford Burnham Prebys, bring us one step closer to understanding the root cause of the disease.

Brain protein may help protect against Alzheimer’s disease  

Previous research from Huang and his colleagues showed that a neuronal protein called SORLA helps reduce production of toxic amyloid beta protein that accumulates and leads to Alzheimer’s disease. Given this important role, Huang decided to dig deeper to understand SORLA’s “job” inside the brain.

In a paper featured on the cover of The Journal of Neuroscience, Huang and his team analyzed mice that produce high levels of SORLA and studied the effects of enhancing SORLA on the brain. This work showed that higher levels of SORLA resulted in elongated neurites, structures that extend from neurons, and improved the repair and regeneration of axons—the cable-like fibers that neurons use to communicate. These findings suggest that drugs that increase levels of SORLA might help protect the brain against Alzheimer’s disease and may even help people with a spinal cord injury. 

Huang describes the findings as “the tip of the iceberg” and is eager to learn more about this important protein—with the ultimate goal of identifying potential targets for drugs that could slow the progression of Alzheimer’s disease. 

A new model for studying Alzheimer’s disease 

Many of the mutations associated with Alzheimer’s disease are found in a brain cell type called microglia. However, unlike other cells, mouse microglia are very different from human microglia. Because scientists primarily use mouse models to understand disease, this difference limits their ability to understand how microglial mutations lead to Alzheimer’s disease.  

To overcome this hurdle, Huang and his team took on the formidable task of creating human stem cell lines that contain Alzheimer’s mutations found in human microglia. The scientists then tracked the downstream effects of these mutations in the cells, including epigenetic and gene expression changes, which revealed many new, previously unknown relationships between Alzheimer’s-associated genes. The findings were published in the Journal of Experimental Medicine

More studies are needed to fully understand the how these interactions alter the course of Alzheimer’s disease—which can now be answered using this new model. Huang, who describes the work as “one of the most challenging and ambitious projects I’ve worked on so far” believes the cell line may also be used to help screen for potential Alzheimer’s disease drugs. 
 

Institute News

Rett Syndrome Foundation funds a potential cure

AuthorSusan Gammon
Date

April 23, 2020

The research may lead to a major step toward a cure.

Rett syndrome is a neurodevelopmental disorder that affects almost all aspects of a child’s life, from walking to eating to intellectual capability. There is no cure for the disease, which occurs mostly in girls, and treatments are aimed at slowing the loss of abilities and alleviating the debilitating symptoms. 

Jing Crystal Zhao, PhD, associate professor at Sanford Burnham Prebys, has received new funding from the Rett Syndrome Foundation to find ways to reverse the changes in a gene that causes Rett syndrome. The research may lead to a major step toward a cure.

“I’m very grateful to the Rett Syndrome Foundation, and excited to begin this project,” says Zhao. “While Rett syndrome may not be well known among the general public, our research may lead to treatments to improve the lives of patients around the world.”

More than 90% of Rett Syndrome cases are caused by genetic changes in a gene called MECP2. Every female carries two copies of the MECP2 gene. Rett syndrome patients carry both a normal and a mutant copy of MECP2. Unfortunately, in some cells, the normal copy of MEPC2 becomes inactive due to a biological process called X-chromosome inactivation—a process that occurs in females—and this leads to Rett syndrome. 

“Recent studies suggest that reversing X-chromosome inactivation could reactivate the normal copy of the MECP2 gene,” says Zhao. “We have identified an DNA element that plays a key role in X-chromosome inactivation. We are now going to test if we can block this element and restore the silent MECP2 gene, which could be life changing. 

“Our aim is to help individuals regain the skills and abilities stolen by Rett syndrome,” adds Zhao. “This award takes us closer to that goal.” 
 

Institute News

Top neuroscientists gather at Sanford Burnham Prebys’ annual symposium

AuthorMonica May
Date

November 18, 2019

A mother who no longer remembers her son. A daughter who took doctor-prescribed pain medication and slipped into addiction. A father who has trouble grasping a pen and eventually becomes unable to walk. Neurological disorders are some of the most painful and complex conditions our society faces today. Yet much about the brain remains unknown, hindering our ability to help people with these disorders.

To help shed light on the brain’s mysteries, on November 1, 2019, more than 250 neuroscientists gathered at Sanford Burnham Prebys’ one-day symposium to share their latest discoveries. Organized by professors Jerold Chun, MD, PhD; Randal Kaufman, PhD; Barbara Ranscht, PhD; and Huaxi Xu, PhD, the event attracted scientists from around the world eager to learn more about biological clues that are leading to effective therapies. Read the full list of the invited speakers and their talks.

“Nearly every day we read about the toll neurological diseases such as Alzheimer’s, dementia, mental health disorders and more take on our society,” said Kristiina Vuori, MD, PhD, president of Sanford Burnham Prebys, in her introductory address. “Our symposium brings together scientists at the frontiers of brain research who share their latest discoveries to open new paths toward new and better treatments.”

More than 50 million Americans are affected by neurological disorders, including Alzheimer’s disease, dementia, addiction and more, according to the National Institute of Neurological Disorders and Stroke. Most of these conditions are not well addressed by current medicines.

At the symposium, world-renowned scientists from Stanford University, Mount Sinai, University of Vienna and other top-tier institutes gave talks describing their strategies to uncover the molecular basis of brain disorders and how these discoveries are advancing potential therapies. A national plan to address Alzheimer’s and other dementia types was described by Eliezer Masliah, MD, the National Institute of Aging’s director of the Division of Neuroscience.

“This was my first scientific conference, and it was perfect for learning about a wide range of cutting-edge brain research,” said attendee Jaclyn Beck, a PhD student at UC Irvine who studies the role of the brain’s immune cells, called microglia, in Alzheimer’s disease. “I have several pages of notes from the talks detailing findings I want to investigate and people I want to contact.”

For the past 40 years, our Institute has invited leading experts on one scientific topic to share their latest research at an annual symposium. By encouraging connection and collaboration, we hope to inspire insights that improve human health. The 41st annual symposium will take place in November 2020 and focus on the biology of organelles, specialized pouches within cells that carry out critical functions such as generating power and breaking down waste, and its role in health and disease.

Institute News

10 questions for Alzheimer’s expert Jerold Chun of Sanford Burnham Prebys

AuthorMonica May
Date

September 21, 2019

Alzheimer’s is one of the most frightening diseases of our time. Of the top 10 causes of death in the U.S., it is the only disease for which no effective or preventative treatment exists. Recent clinical trial failures have only deepened the pain of patients and their families.

To learn about the state of Alzheimer’s research in the wake of these setbacks—and whether there is hope on the horizon—we caught up with Alzheimer’s expert Jerold Chun, MD, PhD, professor and senior vice president of Neuroscience Drug Discovery at Sanford Burnham Prebys. Chun and his team recently published a Nature study that suggests a potential Alzheimer’s treatment may be closer than we think. 

  1. Why has Alzheimer’s disease become so prevalent? Are we better at diagnosing the disease?
    The number of people with Alzheimer’s disease is rising because of the aging Baby Boomers generation—which makes up more than 20% of the U.S. population. As a result, the number of those living with the condition is projected to more than double by 2050 to nearly 14 million people. This will place an incredible economic and social burden on our society—unless a treatment is found.
  2. Are there any treatments that work for Alzheimer’s disease?
    No disease-modifying therapies exist. The medicines a patient can receive today just treat symptoms. For example, cholinesterase inhibitors and N-methyl D-aspartate antagonists treat cognitive symptoms, such as memory loss, confusion and problems with thinking and reasoning—but they aren’t able to stop the disease. 
  3. Is it possible to prevent Alzheimer’s?
    Multiple studies from this year’s Alzheimer’s Association International Conference centered on this topic. Evidence suggests that adopting healthy lifestyle choices such as eating a healthy diet, not smoking, exercising regularly and stimulating the mind may decrease the risk of cognitive decline and dementia.

    It is encouraging to know that preventing Alzheimer’s may be partially within our control. However, it is undeniable that even individuals who live a healthy lifestyle will still develop Alzheimer’s. We need to remain laser focused on developing effective preventions and treatments.

  4. Do we know the cause of Alzheimer’s? What are the latest theories?
    In short, no. We know that clumps of amyloid-beta and tau proteins in the brain are linked to the disease. We also know that in rare cases genes are involved, because Alzheimer’s can run in families—but this accounts for less than 1% of cases. New research points to unique gene changes within the brain, called somatic gene recombination, as a new potential factor. Some data also implicate aspects of the immune system. It’s most likely that multiple factors lead to disease—and that an effective treatment will tackle Alzheimer’s from several angles.
  5. How would you describe the pipeline of Alzheimer’s treatments in development?
    The pipeline of Alzheimer’s treatments is in dire need of expansion. As of February 2019, only 132 drugs were under evaluation in clinical trials. Nearly half of these compounds target beta-amyloid. 

    For comparison, there are nearly 4,000 compounds under development for cancer—which affects almost three times as many Americans each year. We certainly need to continue to invest in cancer treatments—but clearly there is an urgent need to fill the Alzheimer’s pipeline, and an even greater need to find an approach that actually works.

  6. Tell us more about your research. What did you find? What are the next steps? 
    In school we learned that all cells have the same DNA. However, in our recent research we found that in the brains of patients, the DNA in the Alzheimer’s-linked APP gene can be “mixed and matched” into many different, new forms, some of which aren’t found in healthy individuals. To create these new gene variants, reverse transcriptase—best known as an enzyme infamously used by HIV—is required. This suggests that existing HIV medications—called reverse transcriptase inhibitors—which halt reverse transcriptase, might be useful as a near-term treatment for Alzheimer’s disease. A doctor can prescribe these medicines now as an “off-label” use for the treatment of Alzheimer’s disease. However, prospective clinical trials are needed to test the efficacy and side-effect profiles of these medicines in actual Alzheimer’s disease patients.
  7. Are humans the only species that get Alzheimer’s disease? 
    To our knowledge, yes. No other animal has the intellectual and cognitive capacity exhibited by humans. For this reason, scientists have developed animal models that exhibit symptoms and pathologies that approximate the disease. 
  8. How far away are we from an effective Alzheimer’s treatment? Years or decades? 
    What excites me about my team’s findings is that, if true, a partially effective treatment may be available now. Reverse transcriptase inhibitors are medicines currently used to treat HIV and hepatitis B, and have been safely used for 30 years with millions of patient-years of experience. New medicines based on this approach could lead to next-generation drugs with better efficacy and safety.

    Other agents in the Alzheimer’s pipeline currently in development are many years away from an effective treatment. And, it could take an additional 30 years for such agents to have the same level of proven safety as reverse transcriptase inhibitors. Nevertheless, new therapeutics must be pursued. Hopefully, our adult children will have great medical options in their future.

  9. What is the biggest hurdle to developing an Alzheimer’s treatment? 
    A major hurdle is securing funding for early, innovative research. The National Institutes of Health (NIH) is granting more funding than ever before to tackle this disease. However, many people aren’t aware that the NIH overwhelmingly finances projects that are scientifically conservative, which in the case of Alzheimer’s disease has failed to produce effective medicines. Funding that enables scientists to explore new, bold frontiers can be transformational in leading to important advances. This is an area where philanthropic donations can have a major impact—especially now, as the field strives to “think outside of the amyloid box” and explore new approaches.
  10.  Are you hopeful for the future? Why or why not?
    I am absolutely hopeful for the future. Advances in fundamental brain science will lead to new treatments for Alzheimer’s disease. Our work will hopefully be a start to a world where our children don’t have to live in fear of this disease.

About Jerold Chun 
Jerold Chun, MD, PhD, is a world-renowned neuroscientist who seeks to understand the brain and its diseases. His research has discovered genomic mosaicism and somatic gene recombination, surprising phenomena whereby cells in the brain actually have different genomic DNA sequences that can change with disease states. Chun’s research continues to shed light on Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and other neurodegenerative diseases as well as neuropsychiatric disorders and substance abuse.

Institute News

Antimicrobial protein implicated in Parkinson’s disease

AuthorMonica May
Date

July 17, 2019

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.