Dr Colin Mahoney

Dr Colin Mahoney, Senior Research Fellow and Neurologist, The University of Sydney.

Colin is a clinical academic who works on translational research across the spectrum of neurodegenerative disease. In particular he focuses on motor neurodegenerations and Frontotemporal Dementia. Colin trained as a clinician at University College Dublin and completed a neurology elective at Harvard Medical School. He completed specialist training in neurology at the National Hospital for Neurology and Neurosurgery, United Kingdom and Royal Prince Alfred Hospital, Sydney. In addition, he has undertaken fellowships in cognitive neurology at the Dementia Research Centre, UCL and additional neuromuscular training in under the direction of Prof Matthew Kiernan in Sydney. Colin holds a PhD in neuroimaging from University College London. His current research interests are focus on integrating multimodal biomarkers to diagnose and monitor neurodegenerative conditions earlier and more accurately. Increasingly he has become focused on developing new clinical trials, including new approaches to clinical trials utilising multidrug "platform" trial approaches.

Forefront Group:

  • ForeFront MND Group

Affiliate Organisations

University of Sydney, BMC/Royal Prince Alfred Hospital Motor Neuron Disease and Frontotemporal Dementia Clinic


  • Neuroimaging
  • Clinical Biomarkers
  • Clinical Trials

Neurodegeneration of interest:

Frontotemporal Dementia, Motor Neuron Disease, Early-onset Dementia

Specific Skills:

  • Consultant Neurologist
  • Fellowships in cognitive neurology and neuromuscular neurology
  • PhD in Neuroimaging


  • Translating biomarkers to the beside, a precision medicine approach to clinical trials in Frontotemporal Lobar Degeneration FTLD and Motor Neuron disease
  • Translating biomarkers to the beside, a precision medicine approach to clinical trials in Frontotemporal Lobar Degeneration FTLD and Motor Neuron disease
  • Utilising multi-modal connectivity and artificial intelligence to track disease progression in ALS
  • Therapeutic Nanocatalysis to Slow Disease Progression of Amyotrophic Lateral Sclerosis (ALS) (RESCUE-ALS)
  • An Efficacy and Safety Study of Ravulizumab in ALS Participants

Project - Translating biomarkers to the beside, a precision medicine approach to clinical trials in Frontotemporal Lobar Degeneration FTLD and Motor Neuron disease

Research Project Abstract

The proposed study aims to collate a multimodal clinical repository including clinical data, biofluid data, neurophysiological data and neuroimaging and combine this data to develop improved multimodal measures of disease progression in MND and FTD. Using a clinical dataset of over 400 unique participants we aim to identify new subgroups, and therefore improve the predictive power of these biomarkers. Importantly this will allow identification of potential cohorts of participants who may respond to particular interventions, allowing a move towards more precision medicine in these areas. In addition, we will collect prospective novel clinical neuroimaging data, neurophysiological data and clinical data to test new hypothesis with regards to the some of the earliest disease pathobiology in those with MND and FTD.

Project with a disease tag

MND, FTD, and early onset dementia

Challenges within the field

Delay to diagnosis is a major issue, resulting in significant anxiety for patients and delayed access to treatment. This work aims to develop faster ways to diagnose these life limiting conditions and improve the power within drug trials to detect a clinical benefit from novel therapies.

Research Project Description

Clinical "bedside" biomarkers: we will collect detailed data on the clinical neurological finding in those with ALS and FTD. In particular we will identify if novel clinical metrics (such as a composite score reflecting upper and lower motor clinical burden) impact disease progression

Novel clinical measures: we will develop novel measure of disease burden in ALS, with a particular emphasis on non-motor symptoms. We will devise easy to use tools to capture the impact of non-motor symptoms in ALS.

Neuroimaging measures: advanced neuroimaging will be acquired cross-sectionally and longitudinally to establish profiles of neurodegeneration in those with ALS and FTD. Novel approaches to regional disease spread will be applied to better understand the temporal clinical evolution of ALS and FTD

Multimodal analysis: we will combine clinical and neuroimaging datasets to identify the brain basis for the clinical symptoms experienced by patients, providing important insights into disease evolution in ALS and FTD, as well as validating the potential of novel neuroimaging biomarkers.

Translation research: building on the above approaches, we will integrate our research into clinical trials designs to establish the utility of these potential clinical and neuroimaging biomarkers as potential outcome measures for future clinical trial design

Research Objectives

  • To identify neuroimaging biomarkers that best identify and track change in the early MND and FTD
  • Develop innovative biomarkers which can be applied to clinical trials as novel outcome measures.

Key Publications from this project

  • Huynh W, Ahmed R, Mahoney CJ, Nguyen C, Tu S, Caga J, Loh P, Lin CS, Kiernan MC. (2020). The impact of cognitive and behavioral impairment in amyotrophic lateral sclerosis. Expert Rev Neurother Mar;20(3):281-293; doi: 10.1080/14737175.2020.1727740.
  • Mahoney CJ, Kiernan MC. (2020). Expanding the availability of medications for amyotrophic lateral sclerosis in Australia. Med J Aust Mar;212(4):189-189.e1; doi: 10.5694/mja2.50482.
  • Mahoney CJ, Ahmed RM, Huynh W et al. (2021). Pathophysiology and Treatment of Non-motor Dysfunction in Amyotrophic Lateral Sclerosis. CNS Drugs 35, 483–505; doi: 10.1007/s40263-021-00820-1.
  • Huynh W, Tu S, Mahoney CJ, Schwartz R, Kiernan MC. (2021). Mills Syndrome: Clinical and Radiologic Asymmetry. Neurology 96:677-678; doi: 10.1212/WNL.0000000000011710
  • Caga J, Tu S, Dharmadasa T, Tse NY, Zoing MC, Huynh W, Mahoney CJ, Ahmed RM, Kiernan MC. (2021). Apathy is associated with parietal cortical-subcortical dysfunction in ALS. Cortex 02(21):029 doi: 10.1016/j.cortex.2021.02.029.
  • Nguyen C, Caga J, Mahoney CJ, Kiernan MC, Huynh W. (2021). Behavioural changes predict poorer survival in amyotrophic lateral sclerosis. Brain Cogn Jun;150:105710; doi: 10.1016/j.bandc.2021.105710.
  • Mahoney CJ, Dharmadasa T, Huynh W, Halpern JP, Vucic S, Mowat D, Kiernan MC. (2020). A novel phenotype of hereditary spastic paraplegia type 7 associated with a compound heterozygous mutation in paraplegin. Muscle Nerve, 62: E44-E45; doi: 10.1002/mus.26882