Science Current Events | Science News | Brightsurf.com
 

Lou Gehrig's disease: From patient stem cells to potential treatment strategy in one study

October 25, 2013
Although the technology has existed for just a few years, scientists increasingly use "disease in a dish" models to study genetic, molecular and cellular defects. But a team of doctors and scientists led by researchers at the Cedars-Sinai Regenerative Medicine Institute went further in a study of Lou Gehrig's disease, a fatal disorder that attacks muscle-controlling nerve cells in the brain and spinal cord.

After using an innovative stem cell technique to create neurons in a lab dish from skin scrapings of patients who have the disorder, the researchers inserted molecules made of small stretches of genetic material, blocking the damaging effects of a defective gene and, in the process, providing "proof of concept" for a new therapeutic strategy - an important step in moving research findings into clinical trials.

The study, published Oct. 23 in Science Translational Medicine, is believed to be one of the first in which a specific form of Lou Gehrig's disease, or amyotrophic lateral sclerosis, was replicated in a dish, analyzed and "treated," suggesting a potential future therapy all in a single study.

"In a sense, this represents the full spectrum of what we are trying to accomplish with patient-based stem cell modeling. It gives researchers the opportunity to conduct extensive studies of a disease's genetic and molecular makeup and develop potential treatments in the laboratory before translating them into patient trials," said Robert H. Baloh, MD, PhD, director of Cedars-Sinai's Neuromuscular Division in the Department of Neurology and director of the multidisciplinary ALS Program. He is the lead researcher and the article's senior author.

Laboratory models of diseases have been made possible by a recently invented process using induced pluripotent stem cells - cells derived from a patient's own skin samples and "sent back in time" through genetic manipulation to an embryonic state. From there, they can be made into any cell of the human body.

The cells used in the study were produced by the Induced Pluripotent Stem Cell Core Facility of Cedars-Sinai's Regenerative Medicine Institute. Dhruv Sareen, PhD, director of the iPSC facility and a faculty research scientist with the Department of Biomedical Sciences, is the article's first author and one of several institute researchers who participated in the study.

"In these studies, we turned skin cells of patients who have ALS into motor neurons that retained the genetic defects of the disease," Baloh said. "We focused on a gene, C9ORF72, that two years ago was found to be the most common cause of familial ALS and frontotemporal lobar degeneration, and even causes some cases of Alzheimer's and Parkinson's disease. What we needed to know, however, was how the defect triggered the disease so we could find a way to treat it."

Frontotemporal lobar degeneration is a brain disorder that typically leads to dementia and sometimes occurs in tandem with ALS.

The researchers found that the genetic defect of C9ORF72 may cause disease because it changes the structure of RNA coming from the gene, creating an abnormal buildup of a repeated set of nucleotides, the basic components of RNA.

"We think this buildup of thousands of copies of the repeated sequence GGGGCC in the nucleus of patients' cells may become "toxic" by altering the normal behavior of other genes in motor neurons," Baloh said. "Because our studies supported the toxic RNA mechanism theory, we used two small segments of genetic material called antisense oligonucleotides - ASOs - to block the buildup and degrade the toxic RNA. One ASO knocked down overall C9ORF72 levels. The other knocked down the toxic RNA coming from the gene without suppressing overall gene expression levels. The absence of such potentially toxic RNA, and no evidence of detrimental effect on the motor neurons, provides a strong basis for using this strategy to treat patients suffering from these diseases."

Researchers from another institution recently led a phase one trial of a similar ASO strategy to treat ALS caused by a different genetic mutation and reportedly uncovered no safety issues.

Clive Svendsen, PhD, director of the Regenerative Medicine Institute and one of the article's authors, has studied ALS for more than a decade. "ALS may be the cruelest, most severe neurological disease, but I believe the stem cell approach used in this collaborative effort holds the key to unlocking the mysteries of this and other devastating disorders. Within the Regenerative Medicine Institute, we are exploring several other stem cell-based strategies in search of treatments and cures," he said, adding that ALS affects 30,000 to 50,000 people in the U.S., but unlike other neurodegenerative diseases, it is almost always fatal, usually within three to five years.

Svendsen recently received a $17.8 million grant from the California Institute for Regenerative Medicine. In collaboration with Baloh and the ALS clinical team at Cedars-Sinai, this study will support a novel stem cell and growth factor therapy for ALS.

###

Researchers from UCLA; the Mayo Clinic in Jacksonville, Fla.; the University of California, San Diego; Washington University School of Medicine in St. Louis, Mo.; and Isis Pharmaceuticals contributed to the C9ORF72 study.

The research was supported by National Institutes of Health grants NS055980, NS069669, NIH-U24NS07837; and California Institute of Regenerative Medicine grant RT2-02040. Baloh holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. Analytical work was partially supported by the UCLA Muscular Dystrophy Core Center funded by the National Institute of Arthritis, Musculoskeletal and Skin Disorders (P30 AR057230) within the Center for Duchenne Muscular Dystrophy at UCLA.

Citation: Science Translational Medicine, "Targeting RNA foci reduces pathology in iPSC-derived motor neurons from C9ORF72 repeat patients."

Cedars-Sinai Medical Center


Related Stem Cells Current Events and Stem Cells News Articles


Signaling molecule crucial to stem cell reprogramming
While investigating a rare genetic disorder, researchers at the University of California, San Diego School of Medicine have discovered that a ubiquitous signaling molecule is crucial to cellular reprogramming, a finding with significant implications for stem cell-based regenerative medicine, wound repair therapies and potential cancer treatments.

The cellular origin of fibrosis
Harvard Stem Cell Institute scientists at Brigham and Women's Hospital have found the cellular origin of the tissue scarring caused by organ damage associated with diabetes, lung disease, high blood pressure, kidney disease, and other conditions.

Pluripotent cells created by nuclear transfer can prompt immune reaction, researchers find
Mouse cells and tissues created through nuclear transfer can be rejected by the body because of a previously unknown immune response to the cell's mitochondria, according to a study in mice by researchers at the Stanford University School of Medicine and colleagues in Germany, England and at MIT.

Nail stem cells prove more versatile than press ons
There are plenty of body parts that don't grow back when you lose them. Nails are an exception, and a new study published in The Proceedings of the National Academy of Sciences (PNAS) reveals some of the reasons why.

Researchers Characterize a Protein Mutation that Alters Tissue Development in Males Before Birth
Case Western Reserve researchers have identified a protein mutation that alters specific gender-related tissue in males before birth and can contribute to the development of cancer as well as other less life-threatening challenges.

Cardiac stem cell therapy may heal heart damage caused by Duchenne muscular dystrophy
Researchers at the Cedars-Sinai Heart Institute have found that injections of cardiac stem cells might help reverse heart damage caused by Duchenne muscular dystrophy, potentially resulting in a longer life expectancy for patients with the chronic muscle-wasting disease.

A new approach to fighting chronic myeloid leukemia
Chronic myeloid leukemia develops when a gene mutates and causes an enzyme to become hyperactive, causing blood-forming stem cells in the bone marrow to grow rapidly into abnormal cells.

IU researchers identify key mechanism and potential target to prevent leukemia
Researchers have identified two proteins that appear crucial to the development -- and patient relapse -- of acute myeloid leukemia. They have also shown they can block the development of leukemia by targeting those proteins.

Humans' big brains might be due in part to newly identified protein
A protein that may partly explain why human brains are larger than those of other animals has been identified by scientists from two stem-cell labs at UC San Francisco, in research published in the November 13, 2014 issue of Nature.

Jackson Laboratory researchers discover lung regeneration mechanism
A research team led by Jackson Laboratory Professors Frank McKeon, Ph.D., and Wa Xian, Ph.D., reports on the role of certain lung stem cells in regenerating lungs damaged by disease.
More Stem Cells Current Events and Stem Cells News Articles

Stem Cells: An Insider's Guide

Stem Cells: An Insider's Guide
by Paul Knoepfler (Author)


Stem Cells: An Insider's Guide is an exciting new book that takes readers inside the world of stem cells guided by international stem cell expert, Dr. Paul Knoepfler. Stem cells are catalyzing a revolution in medicine. The book also tackles the exciting and hotly debated area of stem cell treatments that are capturing the public's imagination. In the future they may also transform how we age and reproduce. However, there are serious risks and ethical challenges, too. The author's goal with this insider's guide is to give readers the information needed to distinguish between the ubiquitous hype and legitimate hope found throughout the stem cell world. The book answers the most common questions that people have about stem cells. Can stem cells help my family with a serious medical problem...

Stem Cells For Dummies

Stem Cells For Dummies
by Lawrence S.B. Goldstein (Author), Meg Schneider (Author)


The first authoritative yet accessible guide to this controversial topic Stem Cell Research For Dummies offers a balanced, plain-English look at this politically charged topic, cutting away the hype and presenting the facts clearly for you, free from debate. It explains what stem cells are and what they do, the legalities of harvesting them and using them in research, the latest research findings from the U.S. and abroad, and the prospects for medical stem cell therapies in the short and long term. Explains the differences between adult stem cells and embryonic/umbilical cord stem cells Provides both sides of the political debate and the pros and cons of each side's opinions Includes medical success stories using stem cell therapy and its promise for the future Comprehensive and...

Stem Cells: A Very Short Introduction

Stem Cells: A Very Short Introduction
by Jonathan Slack (Author)


Embryonic stem cells have been hot-button topics in recent years, generating intense public interest as well as much confusion and misinformation. In this Very Short Introduction, leading authority Jonathan Slack offers a clear and informative overview of stem cells--what they are, what scientists do with them, what stem cell therapies are available today, and how they might be used in the future. Slack explains the difference between embryonic stem cells, which exist only in laboratory cultures, and tissue-specific stem cells, which exist in our bodies, and he discusses how embryonic stem cells may be used in the future to treat such illnesses as diabetes, Parkinson's disease, heart disease, spinal trauma, and retinal degeneration. But he stresses that, despite important advances, the...

Cracking the Stem Cell Code: Adult Stem Cells Hold the Promise of Miraculous Wellness

Cracking the Stem Cell Code: Adult Stem Cells Hold the Promise of Miraculous Wellness
by Christian Drapeau (Author)


Cracking the Stem Cell Code demystifies the most important scientific breakthrough of our times. It reveals the far reaching potential of Adult Stem Cells in human health and wellness and looks at what’s new, what’s real and what’s next in stem cell science.

Essentials of Stem Cell Biology, Third Edition

Essentials of Stem Cell Biology, Third Edition
by Robert Lanza (Editor), Anthony Atala (Editor)


First developed as an accessible abridgement of the successful Handbook of Stem Cells, Essentials of Stem Cell Biology serves the needs of the evolving population of scientists, researchers, practitioners, and students embracing the latest advances in stem cells. Representing the combined effort of 7 editors and more than 200 scholars and scientists whose pioneering work has defined our understanding of stem cells, this book combines the prerequisites for a general understanding of adult and embryonic stem cells with a presentation by the world's experts of the latest research information about specific organ systems. From basic biology/mechanisms, early development, ectoderm, mesoderm, endoderm, and methods to the application of stem cells to specific human diseases, regulation and...

The Stem Cell Hope: How Stem Cell Medicine Can Change Our Lives

The Stem Cell Hope: How Stem Cell Medicine Can Change Our Lives
by Alice Park (Author)


A landmark book by the senior science writer at Time magazine introduces us to a medical breakthrough that can save our lives. 

Few people know much about stem cell research beyond the ethical questions raised by using embryos. But in the last decade, stem cell research has made huge advances toward eliminating some of our most intractable diseases. Now this sweeping and accessible book introduces us to this cutting-edge science that will revolutionize medicine and change the way we think about and treat disease. 

Alice Park takes us from stem cell's controversial beginnings to the recent electrifying promise of being able to create the versatile cells without using embryos at all. She shows us how stem cells give researchers an unprecedented ability to study disease...

Stem Cells, Second Edition: Scientific Facts and Fiction

Stem Cells, Second Edition: Scientific Facts and Fiction
by Christine Mummery (Author), Anja van de Stolpe (Author), Bernard Roelen (Author), Hans Clevers (Author)


The second edition of Stem Cells: Scientific Facts and Fiction provides the non-stem cell expert with an understandable review of the history, current state of affairs, and facts and fiction of the promises of stem cells. Building on success of its award-winning preceding edition, the second edition features new chapters on embryonic and iPS cells and stem cells in veterinary science and medicine. It contains major revisions on cancer stem cells to include new culture models, additional interviews with leaders in progenitor cells, engineered eye tissue, and xeno organs from stem cells, as well as new information on "organs on chips" and adult progenitor cells. In the past decades our understanding of stem cell biology has increased tremendously. Many types of stem cells have been...

Human Stem Cell Manual, Second Edition: A Laboratory Guide

Human Stem Cell Manual, Second Edition: A Laboratory Guide
by Suzanne Peterson (Editor), Jeanne F. Loring (Editor)


This manual is a comprehensive compilation of "methods that work" for deriving, characterizing, and differentiating hPSCs, written by the researchers who developed and tested the methods and use them every day in their laboratories. The manual is much more than a collection of recipes; it is intended to spark the interest of scientists in areas of stem cell biology that they may not have considered to be important to their work.  The second edition of the Human Stem Cell Manual is an extraordinary laboratory guide for both experienced stem cell researchers and those just beginning to use stem cells in their work.Offers a comprehensive guide for medical and biology researchers who want to use stem cells for basic research, disease modeling, drug development, and cell therapy...

The Amazing Power of STEM CELL NUTRITION: How to Enhance Your Natural Repair System Today

The Amazing Power of STEM CELL NUTRITION: How to Enhance Your Natural Repair System Today
by MD, Dr. Allan C. Somersall PhD (Author)


Everybody has stem cells; everybody uses stem cells; everybody uses stem cells every day; stem cells work… and they work every time! This is a good story to tell in our generation. It’s a story in two parts. First, there is the Natural Renewal System of the body which involves the release of those stem cells from the bone marrow. They then traffic to tissues in need where they migrate out, then proliferate and differentiate to become cells of each particular tissue, thereby providing an effective means for renewal and repair. "That's what nature does already - it is now proven basic Stem Cell physiology." Second, dietary intervention through Stem Cell Nutrition is now available to enhance this intrinsic process in a mild but significant way, thereby making the promotion of...

The Stem Cell Theory of Renewal: Demystifying the Most Dramatic Scientific Breakthrough of Our Time

The Stem Cell Theory of Renewal: Demystifying the Most Dramatic Scientific Breakthrough of Our Time
by Christian Drapeau (Author)


Are the functions of Adult Stem Cells really the most dramatic scientific breakthrough of our times? Visionary Stem Cell Scientist and Stem Cell Nutrition expert Christian Drapeau says 'Absolutely Yes' as he explains the science and implications behind the body's natural renewal system. Adult Stem Cells in your bone marrow constitute the natural healing system of your body. Wherever there is an injury or damage to any organ, stem cells are released from the bone marrow. They migrate to that organ and become healthy cells of that organ, literally repairing the damaged tissue. The implications of new developments in Adult Stem Cell science for health and wellness are mind boggling.

© 2014 BrightSurf.com