Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

First Animal Model of Adult-Onset SMA Sheds Light on Disease Progression and Treatment

Published: Thursday, September 12, 2013
Last Updated: Thursday, September 12, 2013
Bookmark and Share
Another proof of principle for TSUNAMI method in modeling spinal muscular atrophy and other splicing-related illnesses.

A research team at Cold Spring Harbor Laboratory (CSHL) has used a recently developed technology they call TSUNAMI to create the first animal model of the adult-onset version of spinal muscular atrophy (SMA), a devastating motor-neuron illness.

The same team, led by CSHL Professor Adrian R. Krainer, Ph.D., and including scientists from California-based Isis Pharmaceuticals, as well as the University of Southern California and Stony Brook University, succeeded a year ago in using TSUNAMI to make a mouse model of the disease as it is manifest in children. In its most severe form, called Type I SMA, the disease is the leading genetic cause of childhood mortality. Half of infants with Type I SMA die before their second birthday.

Many SMA patients do reach adulthood, however, and on occasion people develop symptoms of the illness only after they have become adults.  Hence the importance of the team’s success, reported online today in EMBO Molecular Medicine.

All patients with SMA, regardless of their age, have a non-functional version of a gene called SMN1, or are missing it entirely. The acronym “SMN” stands for “survival of motor neuron” and suggests why SMA is so serious.  The SMN1 gene encodes a protein, called SMN, that motor neurons need in order to function. Humans have a backup copy of the gene, called SMN2, which produces the same protein, but in much lower amounts.

The body’s manufacture of the SMN protein from the SMN2 gene can limit the impact of SMA.  How much a patient is helped depends on the number of copies of the SMN2 gene they possess. People who have 2-3 copies (Type II SMA) make more protein and survive longer, but can never walk.  Those with 3-4 copies (Type III SMA) usually have a normal lifespan and can walk early in life but accumulate various limiting disabilities over time. Type IV SMA patients have 4 or more copies of the SMN2 gene and don’t experience effects of the disease until adulthood. Yet they often end up in wheelchairs.

Scientists understand why SMN2 does not efficiently yield functional protein: much of its RNA “message” is edited incorrectly, in a process called pre-mRNA splicing. The flaw in the protein’s production is understood. “What we don’t understand is how insufficient levels of the SMN protein in the period following development – i.e., adulthood -- causes pathology in different parts of the body,” Krainer explains. “That’s why we set out to create a model in the adult mouse.”

The Krainer lab’s TSUNAMI technology actually intensifies SMA’s pathological processes in mice bred to mimic the less intense forms of the illness. Thus, it can be used to recapitulate the process by which pathology manifests in different places in the body over the model animal’s lifespan.

“Our efforts to model the adult form of SMA were successful,” says Kentaro Sahashi, M.D., Ph.D., a postdoctoral researcher and neurologist who is first author of the team’s new paper.  “We observed delayed onset of motor neuron dysfunction; we noted also that SMN2 mis-splicing increases during the late stages of SMA, likely accelerating its progression in the body. We noted, importantly, marked liver and heart pathologies that were related to SMA’s progression in adults.”

Drs. Sahashi and Krainer added: “Perhaps most encouraging, our mouse model suggests that only moderate levels of SMN protein are needed in the adult nervous system for normal function.  This means that there may be a broad time window in adult Type IV SMA patients in which to intervene therapeutically.”

Dr. Krainer and colleagues, together with Isis Pharmaceuticals, have identified and characterized an antisense oligonucleotide drug that is currently in Phase 2 clinical trials.

The research described in this release was funded by the National Institutes of Health, the Muscular Dystrophy Association, the SMA Foundation, and the St. Giles Foundation.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More Than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Plant Stem Cell Discovery Points to Increased Yields
Braking signals from the leaves tell stem cells to stop proliferating.
Tuesday, May 17, 2016
New Approach to Treating Genetic Diseases
A team of researchers at CSHL describes their success in paradoxically inhibiting a process cells have evolved to prevent imperfect proteins from being synthesized in the first place.
Wednesday, December 16, 2015
Specific Variations in RNA Splicing Linked to Breast Cancer
Researchers have identified cellular changes that may play a role in converting normal breast cells into tumors. Targeting these changes could potentially lead to therapies for some forms of breast cancer.
Tuesday, October 06, 2015
Scientists Sequence Genome Of Worm That Can Regrow Body Parts
Worm’s genome could lead to better understanding of its regenerative prowess and advance stem cell biology.
Tuesday, September 22, 2015
Tumor Microenvironment Impacts Cancer Subtype Progression
Scientists report that two different mouse models of breast cancer progressed differently based on characteristics of the tumor microenvironment, which is the area of tissue in which the tumor is embedded.
Friday, May 29, 2015
Using CRISPR, Biologists Find a Way to Comprehensively Identify Anti-Cancer Drug Targets
Scientists at CSHL publish CRISPR gene-editing technology in Nature Biotechnology.
Wednesday, May 13, 2015
3-D Culture System for Pancreatic Cancer has Potential to Change Therapeutic Approaches
Organoid technology with human tissue provides a model for full progression of the disease.
Tuesday, January 06, 2015
CSHL Team Finds a Way to Make shRNA Gene Knockdown More Effective
A powerful algorithm that improves the effectiveness of an important research technology.
Thursday, December 11, 2014
Getting More Out of Nature: Genetic Toolkit Finds New Maximum for Crop Yields
An array of gene variants provides “breakthrough benefits” in tomato yield for breeders; other crops next.
Tuesday, November 04, 2014
CSHL Receives $50M to Establish Simons Center for Quantitative Biology
Center will support research and education programs at one of the world’s leading independent biomedical research institutions.
Tuesday, July 08, 2014
Researchers Observe Overlap in Altered Genes Found in Schizophrenia, Autism and ID
Evidence supports theory that some cases of schizophrenia, autism and intellectual disability, malfunctions in some of the same genes are contributing to pathology.
Tuesday, April 29, 2014
Studies Generate ‘Comprehensive’ List of Genes Required to Defend Sex Cells from Transposons
The piRNA pathway protects eggs and sperm from ‘jumping genes’ that can cause developmental defects, sterility.
Monday, May 13, 2013
Boosting Maize Yields with Clever Genetics
A team of plant geneticists at Cold Spring Harbor Laboratory (CSHL) has successfully demonstrated what it describes as a "simple hypothesis" for making significant increases in yields for the maize plant.
Tuesday, February 05, 2013
CSHL Study Uncovers a New Exception to a Decades-Old Rule about RNA Splicing
Discovery alters prevailing view of splicing regulation and has implications for splicing mutations associated with disease.
Thursday, May 24, 2012
CSHL Team Solves a Protein Complex’s Molecular Structure to Explain Role in Gene Silencing
Scientists from Cold Spring Harbor Laboratory and their collaborators at St. Jude’s Research Hospital have discovered new details of how various domains of the protein complex contribute to heterochromatin assembly and gene silencing.
Thursday, December 01, 2011
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!