Skip to main content
Navigate back to homepage
Open search bar.
Open main navigation menu

Main navigation

  • Study
    UCL Portico statue
    Study at UCL

    Being a student at UCL is about so much more than just acquiring knowledge. Studying here gives you the opportunity to realise your potential as an individual, and the skills and tools to thrive.

    • Undergraduate courses
    • Graduate courses
    • Short courses
    • Study abroad
    • Centre for Languages & International Education
  • Research
    Tree-of-Life-MehmetDavrandi-UCL-EastmanDentalInstitute-042_2017-18-800x500-withborder (1)
    Research at UCL

    Find out more about what makes UCL research world-leading, how to access UCL expertise, and teams in the Office of the Vice-Provost (Research, Innovation and Global Engagement).

    • Engage with us
    • Explore our Research
    • Initiatives and networks
    • Research news
  • Engage
    UCL Print room
    Engage with UCL

    Discover the many ways you can connect with UCL, and how we work with industry, government and not-for-profit organisations to tackle tough challenges.

    • Alumni
    • Business partnerships and collaboration
    • Global engagement
    • News and Media relations
    • Public Policy
    • Schools and priority groups
    • Visit us
  • About
    UCL welcome quad
    About UCL

    Founded in 1826 in the heart of London, UCL is London's leading multidisciplinary university, with more than 16,000 staff and 50,000 students from 150 different countries.

    • Who we are
    • Faculties
    • Governance
    • President and Provost
    • Strategy
  • Active parent page: Brain Sciences
    • Study
    • Research
    • About the Faculty
    • Institutes and Divisions
    • Active parent page: News and Events
    • Contact

Motor neuron disease discovery offers new insights into potential treatment targets

Breadcrumb trail

  • Brain Sciences
  • News and Events

Faculty menu

  • Current page: Faculty news
  • Events

Scientists at UCL Institute of Neurology have discovered how certain forms of motor neuron disease begin and progress at cellular and molecular levels, revealing potential new ways to slow down or even stop this process. The team are already working closely with pharmaceutical companies to use this knowledge to develop new treatments for motor neuron disease and other neurodegenerative conditions.

By studying cells from patients with motor neuron disease, also known as amyotrophic lateral sclerosis (ALS), the team from the Francis Crick Institute and UCL Institute of Neurology revealed a detailed picture of how motor neurons - nerve cells in the brain and spinal cord that control our muscles and allow us to move, talk and breathe - decline and die.

The research, published in Cell Reports, also shows that healthy neuron-supporting cells called astrocytes may play a role in the survival of motor neurons in this type of ALS, highlighting their potential role in combating neurodegenerative diseases. The work was co-led by Dr Sonia Gandhi and Dr Rickie Patani, group leaders at the Francis Crick Institute and UCL Institute of Neurology, and consultant neurologists at the National Hospital for Neurology and Neurosurgery, Queen Square.

"Understanding how and why neurons die is clearly vital in neurodegenerative diseases, but part of the puzzle is also understanding the emerging role of astrocytes in this context," said lead author Dr Sonia Gandhi (UCL Institute of Neurology).

The team took skin cells from healthy volunteers and patients with a genetic mutation that causes ALS, and turned them into stem cells capable of becoming many other cell types. Using specific chemical signals, they then 'guided' the stem cells into becoming motor neurons and astrocytes.

"We manipulated the cells using insights from developmental biology, so that they closely resembled a specific part of the spinal cord from which motor neurons arise," said senior author Dr Rickie Patani (UCL Institute of Neurology). "It's like changing the postcode of a house without actually moving it. We were able to create pure, high-quality samples of motor neurons and astrocytes which accurately represent the cells affected in patients with ALS."

Using a range of cellular and molecular techniques, the team tracked motor neurons over time to see what went wrong in the patient-derived cells compared to those from healthy people. They found that an important protein known as TDP-43 leaks out of the nucleus where it belongs, causing a chain reaction that damaged several crucial parts of the cell's 'machinery'. Defining the sequence of molecular events that led to motor neuron death in an experiment using human-derived cells is an important step forward.

"It's a case of the right protein in the wrong place. When TDP-43 leaves the cell nucleus, it causes a series of problems inside the cell that together lead to cell death," said Dr Patani.
Dr Gandhi said: "Knowing when things go wrong inside a cell, and in what sequence, is a useful approach to define the 'critical' molecular event in disease. By modelling the human disease in a dish, we found that this well-recognised event in ALS occurred early, and some time before the neurons showed other signs of stress. One therapeutic approach to stop sick motor neurons from dying could be to prevent proteins like TDP-43 from leaving the nucleus, or try to move them back."

The team suspected that astrocytes from the patients' cells might also be affected, becoming less efficient over time and eventually dying. To test this, they mixed different combinations of healthy and ALS patient-derived motor neurons and astrocytes, and followed their fate using highly sensitive imaging approaches. They found that healthy astrocytes kept sick motor neurons alive and functioning for longer, but sick astrocytes struggled to keep even healthy motor neurons alive.

"Our work, along with other studies of ageing and neurodegeneration, would suggest that the cross-talk between neurons and their supporting cells is crucial in the development and progression of ALS," said Dr Patani.

The research was funded by Wellcome, Cerevance, Grand Challenges, the National Institute for Health Research (NIHR) Queen Square Dementia Biomedical Research Unit and the NIHR University College Hospitals Biomedical Research Centre.

Links

  • Hall, C,Yao, Z, Choi, M, Ule, J, Gandhi, S and Patani, R. Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS. Cell Reports, Volume 19, Issue 9, p1739–1749, 30 May 2017. http://dx.doi.org/10.1016/j.celrep.2017.05.024
  • Dr Rickie Patani's academic profile
  • Dr Sonia Gandhi's academic profile

Image

  • Left images show healthy human motor neurons (far left) and sick ALS motor neurons (centre left); Right shows a protein known as TDP-43 that stays in the nucleus of healthy cells (centre right) but leaks out in sick cells (far right), causing a chain reaction that damages several crucial parts of the cell’s ‘machinery’. Credit: Dr Zhi Yao.

Source

  • Francis Crick Institute

UCL footer

Visit

  • Bloomsbury Theatre and Studio
  • Library, Museums and Collections
  • UCL Maps
  • UCL Shop
  • Contact UCL

Students

  • Accommodation
  • Current Students
  • Moodle
  • Students' Union

Staff

  • Inside UCL
  • Staff Intranet
  • Work at UCL
  • Human Resources

UCL social media menu

  • Link to Soundcloud
  • Link to Flickr
  • Link to TikTok
  • Link to Youtube
  • Link to Instagram
  • Link to Facebook
  • Link to Twitter

University College London, Gower Street, London, WC1E 6BT

Tel: +44 (0) 20 7679 2000

© 2025 UCL

Essential

  • Disclaimer
  • Freedom of Information
  • Accessibility
  • Cookies
  • Privacy
  • Slavery statement
  • Log in