Neurodegenerative diseases affect cells in the nervous system called neurons. Twenty million people worldwide are diagnosed with a neurodegenerative disease each year, and at present they are all progressive and incurable. The Chandran group links clinical activity with laboratory research into two such conditions: multiple sclerosis and motor neurone disease. Measuring disease course and treatment outcomes through disease bio-registers builds an increasingly accurate clinical picture. In parallel, studies in the lab —including using human stem cells—focus on understanding what is going wrong in the neurons and supporting cells called glia. Bringing these two strands together, the group aims to develop novel regenerative therapies and bring them to early-phase clinical trials.
Professor Siddharthan Chandran works in the emerging discipline of Regenerative Neurology. His research combines laboratory activity that includes human stem cells with specialist clinics (multiple sclerosis [MS] and motor neurone disease [MND]) to both study disease as well as undertake early-phase clinical trials.
The ultimate aim is to develop novel regenerative therapies for neurodegenerative disease.
Clinical research, based at the Anne Rowling Regenerative Neurology Clinic, is founded on specialist clinics and linked disease registries to develop a clinical experimental infrastructure for longitudinal studies. Current collaborative clinical projects include:
- Epidemiological studies in MND (SMART-MND) and MS
- MS-SMART – a major MRC-EME-funded clinical trial in secondary progressive MS
- The Voice Bank initiative - using informatics to provide personalised synthetic voices for use in communication aids
- Examining cognitive defects in MS using psychological testing paired with MRI brain scans
Lab research is focused on the glial-neuronal interaction in health and disease. Current approaches include:
- In vitro modelling of TDP43 proteinopathies using patient-derived iPS cells that have been converted into a range of functional neuronal and glial subtypes;
- In vivo modelling of the interactions between inflammation, neurodegeneration and repair in a mouse model of MS (Biozzi-EAE).
At the University of Edinburgh Siddharthan Chandran is Director of the Centre for Clinical Brain Sciences and two philanthropically funded centres: the Euan MacDonald Centre for Motor Neurone Disease Research and Anne Rowling Regenerative Neurology Clinic
Research at CCBS targets the causes, consequences and treatment of major brain disorders.
The Euan MacDonald Centre is a “centre without walls” of 30 researchers across Scotland that seeks to improve the lives of patients living with MND through fundamental discovery research as well as a growing portfolio of patient-centred research projects. A major international collaboration to generate induced pluripotent stem (iPS) cell-derived motor neurones is anchored at CRM.
The Anne Rowling Clinic is a clinical research facility focusing on a wide range of neurological conditions, especially neurodegenerative diseases. Work in the Clinic is closely linked to CRM with the Chandran, ffrench-Constant, Kaji, Kunath and Williams research groups all examining the underpinning biology of these diseases and the technologies required to study them.
Prof Chandran is also Associate Director of the Centre for Brain Development and Repair (CBDR). CBDR is a large-scale India-UK research collaboration between the University of Edinburgh and The Institute for Stem Cell Biology and Regenerative Medicine (inStem) and the National Centre for Biological Sciences (NCBS), Bangalore, India.
- Scottish Motor Neurone Disease Audit, Research and Trials (SMART-MND). This is a collaborative MND Scotland-supported Scotland-wide clinical audit-research programme co-led with Robert Swingler (Dundee).
- Multiple Sclerosis - Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART). The Anne Rowling Clinic is playing a leading role in this major MRC-EME and MS Society-funded clinical trial. The trial is comparing the efficacy of three neuroprotective agents against placebo in secondary progressive MS.
- The Voice Bank project. Many individuals with a neurodegenerative condition lose their voice. Not being able to speak in one's own voice leaves many patients feeling frustrated, entrapped and isolated. With colleagues at the Centre for Speech Technology Research, the Chandran group generating a "bank" of voices that can be mixed using specialised in-house software to create a bespoke, natural-sounding voice - as close as possible to that of the patient - for use in communication aids. For more information see Euan MacDonald Centre Clinical Research.
- Cognition in MS. Symptoms of MS that affect memory, concentration, speech, language or vision are referred to as cognitive symptoms. In collaboration with Dr Thomas Bak (Psychology), the Chandran group uses psychological testing paired with MRI brain scanning to investigate cognitive symptoms in MS. The aim is to discover whether MS disease sub-type differentially affects selective cognitive domains such as vision in addition to "global" slowing of information processing.
- Modelling of MND using induced pluripotent stem (iPS) cells. The Chandran group plays a key role in an international collaboration with Kings College London, Columbia University New York and the University of California San Francisco. Patients with an inherited form of MND caused by mutation in the TDP43 gene donate a skin biopsy, from which the skin cells are converted into induced pluripotent stem (iPS) cells. The Chandran group has developed methodology for the neuronal conversion of these stem cells into a range of functional neuronal and glial subtypes. These are then used to study the molecular and cellular basis of disease and the effects of potential therapeutic drugs.
- David Baker, Queen Mary, University of London (Experimental modelling of MS)
- Tamir Ben-Hur, Hadassah University Hospital, Jerusalem (Experimental modelling of MS)
- Jeremy Chataway, University College, London (Neuroprotection trials in MS)
- Steven Finkbeiner, University of California, San Francisco (Disease modelling in MND)
- Tom Maniatis, Columbia University (Disease modelling in MND)
- Gareth Miles, University of Dundee (Spinal neuronal electrophysiology)
- David Miller, University College London (Imaging and neuroprotection trials in MS)
- Paolo Muraro, Imperial College London (Clinical trial of autologous MSCs in MS)
- Chris Shaw, King's College London (Disease modelling in MND)
- Robert Swingler, Ninewells Hospital and Medical School, Dundee (MND disease register)
- Ludovic Vallier, University of Cambridge (Human stem cell reprogramming)