www.nih.gov Open in urlscan Pro
2406:da00:ff00::3e2:22ab  Public Scan

Form analysis
3 forms found in the DOM

GET https://search.nih.gov/search

<form accept-charset="UTF-8" action="https://search.nih.gov/search" id="search" class="search-form site-search" method="get">
  <div style="margin:0;padding:0;display:inline"><input name="utf8" type="hidden" value="✓"></div>
  <input id="affiliate" name="affiliate" type="hidden" value="nih">
  <label for="query" class="hide">Search the NIH Website</label>
  <input autocomplete="off" class="usagov-search-autocomplete form-field form-field-site-search ui-autocomplete-input" id="query" name="query" type="text" placeholder="Search NIH"><input type="submit" name="commit" value="Search"
    class="form-button form-button-site-search">
</form>

GET https://search.nih.gov/search

<form id="hipsearch" accept-charset="UTF-8" action="https://search.nih.gov/search" method="get" class="search-form">
  <p class="subhead"><label for="query2">Search Health Topics</label></p>
  <div class="input-wrapper">
    <div style="margin:0;padding:0;display:inline"><input name="utf8" type="hidden" value="✓"></div>
    <input id="affiliate" name="affiliate" type="hidden" value="hip">
    <input type="hidden" name="dc" value="940">
    <input autocomplete="off" maxlength="50" class="usagov-search-autocomplete form-field form-field-search ui-autocomplete-input" id="query2" name="query" type="text">
    <input name="commit" type="submit" value="Go" id="searchbutton" class="form-button">
  </div>
</form>

GET https://grants.nih.gov/funding/SearchGuide/transForm-launch2.cfm

<form action="https://grants.nih.gov/funding/SearchGuide/transForm-launch2.cfm" method="get" class="search-form">
  <p class="subhead"><label for="search_nihguide">Search the NIH Guide</label></p>
  <div class="input-wrapper">
    <input name="SearchTerms" type="text" id="search_nihguide" title="Search the NIH Guide" class="form-field form-field-search">
    <input type="submit" name="Search_Guide" value="Go" class="form-button">
    <input name="NoticesToo" type="hidden" value="0">
    <input name="PAsToo" type="hidden" value="1">
    <input name="RFAsToo" type="hidden" value="1">
  </div>
</form>

Text Content

loading


Skip to main content
 * U.S. Department of Health & Human Services


Search the NIH Website
 * NIH Employee Intranet
 * Staff Directory
 * En Español

SearchMenu


SITE MENU

   
 * HomeShow/hide sub-menu
   
 * Health InformationShow/hide sub-menu
    * Health Care Providers & Facilities(link is external)
    * Health Info Lines
    * HealthCare.gov(link is external)
    * Science Education Resources
    * NIH Clinical Research Trials and You
    * Talking to Your Doctor
      
   
   More »
   
   Search Health Topics
   
   
   
   Quick Links
   
    * MedlinePlus Health Info
    * NIH News in Health
    * Wellness Toolkits

   
 * Grants & FundingShow/hide sub-menu
    * Grants Home Page
    * Find Funding
    * Due Dates
    * How to Apply
    * About Grants
    * Policy & Compliance
    * Grants News/Blog
    * Contracts
    * Loan Repayment
   
   More »
   
   Search the NIH Guide
   
   
   
   Quick Links
   
    * RePORT
    * eRA Commons
    * NIH Common Fund

   
 * News & EventsShow/hide sub-menu
    * News Releases
    * Digital Media Kits
    * Media Resources
    * Media Contacts
    * Images and B-roll
    * Events
    * Social Media
   
   More »
   
   Quick Links
   
    * NIH News in Health
    * NIH Research Matters
    * NIH Record

   
 * Research & TrainingShow/hide sub-menu
    * Medical Research Initiatives
    * Science Highlights
    * Science Education
    * Research in NIH Labs & Clinics
    * Training Opportunities
    * Library Resources
    * Research Resources
    * Clinical Research Resources
    * Safety, Regulation and Guidance
   
   More »
   
   Quick Links
   
    * PubMed
    * Stem Cell Information
    * OppNet
    * NIDB
    * NIH Blueprint for Neuroscience Research

   
 * Institutes at NIHShow/hide sub-menu
    * List of Institutes, Centers & Offices
    * NIH Office of the Director
    * Directors of NIH Institutes and Centers
    * NIH Institute and Center Contact Information
   
   More »
   
   Quick Links
   
    * NCI
    * NEI
    * NHLBI
    * NHGRI
    * NIA
    * NIAAA
    * NIAID
    * NIAMS
    * NIBIB
    * NICHD
    * NIDCD
    * NIDCR
    * NIDDK
    * NIDA
    * NIEHS
    * NIGMS
    * NIMH
    * NIMHD
    * NINDS
    * NINR
    * NLM
    * CC
    * CIT
    * CSR
    * FIC
    * NCATS
    * NCCIH
    * OD

   
 * About NIHShow/hide sub-menu
    * Who We Are
    * What We Do
    * Jobs at NIH
    * Visitor Information
    * Frequently Asked Questions
    * Contact Us
      
   
   More »
   
   Quick Links
   
    * The NIH Director
    * The NIH Almanac
    * NIH…Turning Discovery Into Health®
    * Impact of NIH Research
    * Science, Health, and Public Trust
      
      




COVID-19

 * Public health information from CDC
 * Research information from NIH | Español
 * NIH staff guidance on coronavirus (NIH Only)

Hide emergency message


YOU ARE HERE

Home » News & Events » News Releases


NEWS RELEASES

News Release

Monday, January 24, 2022


SILENCING A FAULTY GENE MAY UNCOVER CLUES TO RARE FORMS OF ALS

NIH-funded preclinical study identifies potential therapeutic approach to treat
ALS.

AddThis Sharing Buttons
Share to PrintPrintShare to EmailEmailShare to FacebookFacebookShare to
TwitterTwitterShare to MoreAddThis
A novel drug, designed to silence a gene called FUS, may treat ALS by “knocking
down” disease causing proteins. Shown above are motor neurons from a mouse
treated with the drug.

Using an experimental drug, researchers were able to suppress a mutated
amyotrophic lateral sclerosis (ALS) gene. Studies in mice demonstrate that the
therapy could show promise in treating rare, aggressive forms of ALS caused by
mutations in the fused in sarcoma (FUS) gene. The study, published in Nature
Medicine, was funded in part by the National Institute for Neurological
Disorders and Stroke (NINDS), part of the National Institutes of Health.

“The study models how promising gene-targeting therapies can move expeditiously
from pre-clinical development to clinical testing,” said Amelie Gubitz, Ph.D.,
program director at NINDS. “There is a desperate need for innovative approaches
to treating ALS.”

ALS, also known as Lou Gehrig’s disease, is a fatal neurological disorder that
causes the degeneration of motor neurons in the brain and spinal cord. People
with ALS rapidly lose muscle strength and eventually their ability to move,
swallow, and breathe. Most cases of ALS are sporadic, but at least 10% of cases
are familial, or due to mutations in various genes. Mutations in the gene FUS
cause severe forms of ALS, referred to as FUS-ALS, including a rare type that
begins in adolescence or young adulthood.

In the study, Neil Shneider, M.D., Ph.D., the Claire Tow Associate Professor of
Motor Neuron Disorders and Director of the Eleanor and Lou Gehrig ALS Center at
Columbia University, New York City, and his team delayed the onset of motor
neuron degeneration in mice by using an antisense oligonucleotide drug designed
to silence FUS by blocking cells from making specific proteins. Following
encouraging results, they administered the drug to a patient with ALS.

Compared to normal mice, mice with a mutated FUS gene had higher levels of
insoluble FUS and other ALS-related proteins in their brains and spinal cords.
Mice with higher doses of mutant FUS in motor neurons experienced rapid
neurodegeneration that began early in life, much like FUS-ALS patients.

“The study establishes a mouse model that is highly disease-relevant,” said Dr.
Shneider. “In mice, we found that FUS toxicity was due to a gain of function and
was dose-dependent, suggesting that we could treat FUS-ALS by silencing the FUS
gene.”

In 2019 Dr. Shneider met an individual with ALS in search of therapies that may
help her disease. Inspired by her story, Dr. Shneider teamed up with a
pharmaceutical company to develop a personalized therapy designed to target the
FUS mutation.

In mice, injecting a single dose of the drug into the ventricles, fluid-filled
spaces surrounding the brain, delayed the onset of inflammation and motor neuron
degeneration by six months. The drug also knocked down levels of FUS by 50% to
80% in the brain and spinal cord. Following drug administration, insoluble forms
of other ALS-associated proteins were also cleared.

Under a compassionate use protocol reviewed by the U.S. Food and Drug
Administration, Dr. Shneider administered the drug to the patient it had been
designed for. The patient received repeated infusions of the drug into her
spinal canal for 10 months. During the treatment, the patient’s rate of motor
function deterioration slowed. The patient tolerated the treatment well and
there were no medically adverse effects.

“The study is an example of a precision medicine, bench-to-bedside effort,” said
Dr. Shneider. “We began with the mouse model to establish a rationale for the
drug, conducted efficacy studies in the mouse, moved the drug into a human, and
collected valuable data that was ultimately used to support a larger Phase 3
clinical trial.”

Treatment began more than six months after clinical onset, by which time the
disease had already significantly advanced. As is typical with juvenile-onset
FUS-ALS, the disease progressed rapidly, and the patient died from complications
of the disease.

By studying the patient’s brain and spinal cord tissue, researchers found that
the drug silenced FUS throughout the nervous system and reversed the toxic
nature of FUS and other disease-related proteins. Compared to tissue from
untreated FUS-ALS patients and healthy controls, FUS protein aggregates—a
pathological hallmark of this form of ALS—were sparse, suggesting that they may
have been cleared by the drug. Tissue samples were provided by the New York
Brain Bank of Columbia University.

The protein made from the FUS gene has been shown to be important for various
cellular processes. Prior studies in mice suggest that FUS mutations result in
the production of an abnormal protein that forms clumps, or aggregates, leading
to motor neuron damage. By targeting the faulty gene in a way that suppresses
toxic FUS activity, gene silencing products like the antisense oligonucleotide
drug could potentially reduce or prevent disease progression.

The results were used to support a clinical trial testing the drug in patients
with FUS-ALS (NCT04768972).

This study was supported by grants from the NIH (NS106236), Nancy Perlman, Tom
Klingenstein, and the Judith and Jean Pape Adams Charitable Foundation.

NINDS is the nation’s leading funder of research on the brain and nervous
system. The mission of NINDS is to seek fundamental knowledge about the brain
and nervous system and to use that knowledge to reduce the burden of
neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical
research agency, includes 27 Institutes and Centers and is a component of the
U.S. Department of Health and Human Services. NIH is the primary federal agency
conducting and supporting basic, clinical, and translational medical research,
and is investigating the causes, treatments, and cures for both common and rare
diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health®


ARTICLE

Korobeynikov, V.A., et al. Antisense oligonucleotide silencing of FUS expression
as a therapeutic approach in amyotrophic lateral sclerosis. Nature Medicine,
January 24, 2022. DOI: 10.1038/s41591-021-01615-z(link is external)


MORE INFORMATION

Amyotrophic Lateral Sclerosis (ALS) Information Page

Amyotrophic Lateral Sclerosis (ALS) Fact Sheet

National Institute of Neurological Disorders and Stroke (NINDS)

###




INSTITUTE/CENTER

National Institute of Neurological Disorders and Stroke (NINDS)


CONTACT

Nina Lichtenberg(link sends e-mail)
301-496-5751


CONNECT WITH US

 * Subscribe to news releases
 * RSS Feed





CONNECT WITH US

 * Contact Us
 * Twitter(link is external)
 * Facebook(link is external)
 * Instagram(link is external)
 * YouTube(link is external)
 * Flickr(link is external)
 * More Social Media from NIH


FOOTER

 * NIH Home
 * En Español
 * Site Map
 * Visitor Information
 * Frequently Asked Questions
 * Web Policies and Notices
 * NIH Website Archives

 * Freedom of Information Act
 * No Fear Act
 * HHS Vulnerability Disclosure(link is external)
 * Office of Inspector General(link is external)
 * USA.gov – Government Made Easy(link is external)

NIH…Turning Discovery Into Health®

National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892

U.S. Department of Health and Human Services(link is external)

Back to Top