Professor Matthew Kiernan

Professor Matthew Kiernan, Professor of Medicine, Bushell Chair of Neurology, Co-director of the Brain and Mind Centre, The University of Sydney.

Matthew's clinical research unit is located at the Brain and Mind Centre. He is a Professor of Neurology and Staff Specialist at the Royal Prince Alfred Hospital and a Senior Scientist at Neuroscience Research Australia.

Matthew leads a research group comprised of a team of clinicians, scientists, biomedical engineers, doctors and postdoctoral students with focus on neurological disease. His research team's focus is clinical neurology, in particular disease pathophysiology and treatment strategies of frontotemporal dementia and motor neurone syndromes. Currently his team is investigating the mechanisms and the possible prevention of neurodegeneration in motor neurone disease (MND) also known as amyotrophic lateral sclerosis (ALS); frontotemporal dementia; chemotherapy-induced neurotoxicity; stroke; Machado-Joseph disease; spinal muscular atrophy and other inherited neuropathies. He is also involved in clinical trials investigating potential drug treatments for motor neurone disease, multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. His team's research is linked to the provision of clinical services, particularly the ForeFront Neurology Clinic and associated diagnostic neurophysiology laboratories.

Forefront Group:

  • BMC ForeFront Neurology Research Group Leader
  • Dominantly Inherited Non-Alzheimer Dementias (DINAD) Research Group

Affiliate Organisations

Royal Prince Alfred Hospital, MND Australia, Fight MND, MiNDAUS, Neurosciences Research Australia

Neurodegeneration of interest:

FTD, MND, Spinal muscular atrophy, Kennedy’s disease, Primary lateral sclerosis, Chronic inflammatory demyelinating polyneuropathy, Multifocal motor neuropathy, Isaac’s syndrome


  • Neurologist
  • Neurophysiologist
  • Neurodegeneration

Specific Skills:

  • Medical Practitioner
  • Neurologist
  • Neurophysiologist
  • Medical Scientist
  • Clinical Researcher
  • Neuroscientist

Project - Frontotemporal dementia and motor neurodegenerative syndromes

Disease area:

Neurology, Dementia, MND, FTD

Professor Matthew Kiernan, Associate Professor Susanna Park, Professor Cindy Lin, Professor Steve Vucic, Dr William Huynh, Dr Jaschelle Caga, Associate Professor Rebekah Ahmed, Dr Emma Devenney, Dr Colin Mahoney, Dr Sicong Tu, Dr Antonia Carroll, Sr Margie Zoing, Dr Hannah Timmins, Srestha Mazumder, Professor Michael Barnett, Professor Glenda Halliday


Confirmation of diagnosis and the assessment of regional patterns of neurodegeneration require systematic neuropathology. At disease onset, focal pathology restricted to distinct brain areas is a feature of MND, FTD and related syndromes. Forefront Neurology have introduced a multidisciplinary clinical assessment for MND and FTD patients referred to Royal Prince Alfred Hospital (partner in NHMRC Advanced Health Research and Translation Centre, Sydney Health Partners) and the Brain and Mind Centre, University of Sydney. As such, all patients currently undergo standard clinical, electrodiagnostic, neurophysiological, respiratory and functional grading assessments, a comprehensive core neuropsychological assessment, in addition to a range of behavioural assessments and neuroimaging. Bloods are taken and stored for DNA and biomarker testing. Clinical phenotyping is refined over time through ongoing clinical assessments undertaken by an extended multidisciplinary clinical and research team. The ultimate goal for neurodegenerative research remains to develop a platform for therapeutic intervention with disease-modifying therapies. This requires an understanding of the pathogenesis of the protein abnormality to be treated, as well as the ability to clinically identify the patient with this protein abnormality and specific clinical phenotype.

Challenges within the field

1. To translate research findings in FTD/MND into diagnostic and phenotypic tools that can be utilised in tertiary clinics and broader healthcare settings, nationally and internationally.

2. To develop interventions that alter the traditional disease trajectory, to better understand the cognitive and behavioural changes in early MND and FTD.

Disease heterogeneity suggests that a precision medicine paradigm will be required to realise effective therapy, enabled through incorporation of phenotypic and genotypic information to improve outcomes for individual patients

Key Findings

Recent progress has promoted the transition of neurodegenerative disease to a precision medicine paradigm, enabled through the incorporation of phenotypic and genotypic data to better guide therapy and thereby outcomes for individual patients. Such prediction promotes better targeted therapies for neurodegenerative diseases. Recent progress with precision medicine based on genetically-targeted therapies is anticipated to have a significant impact on the natural history of disease.

Research Objectives:

  • Diagnosis and treatment of Neurological Disease, with specific focus on Frontotemporal Dementia and Motor Neurodegeration Syndrome Program.
  • Investigation of disease pathophysiology and treatment strategies for neurological disorders.
  • Optimise the translation of research findings into improved healthcare practice and policy.

Research Project Description

A critical feature leading to successful therapy development for neurodegenerative syndromes will be to facilitate inclusion of appropriate mechanistic outcome measures into clinical trial programs. Currently there is a disconnect between efforts to develop sensitive and specific mechanistic outcome measures and clinical trial protocol development. Common mechanisms associated with both metabolic dysfunction and neurodegeneration include oxidative stress, inflammation and vascular dysfunction. While there is limited in vivo evidence to suggest that metabolic mechanisms may enhance neurodegeneration, there is emerging data on the metabolic variability associated with MND/FTD that suggests a spectrum of phenotypic metabolic change that may be developed as models. In the least, metabolic changes contribute to patient disability including the muscle wasting, a significant prognostic factor.

Current Key Projects:

  • 2020-2022 NHMRC Medical Research Futures Fund MRFF: ALS Trials Australia (ALSTA) - to develop precision medicine; Kiernan, M, Vucic S, Wray N, Talman P, Needham, M, Schultz, D, Barnett, M, Park, S; $1,700,000
  • 2019-2023 NHMRC Practitioner Fellowship: Developing new therapies for neurodegeneration and dementia; Kiernan MC; National Health and Medical Research Council. $585,270.00
  • 2019 Translating biomarkers to the beside, a precision medicine approach to clinical trials in Frontotemporal Lobar Degeneration (FTLD) and Motor Neuron disease (MND); Mahoney C, Kiernan M; DVC Research/Postdoctoral Research Fellowship Scheme $300,000
  • 2019-2023 NHMRC Partnership Grant: Motor Neurone Disease: Patient centred care for a progressive neurological disease - evidence driving policy; Kiernan MC, Wray N, Talman P, Vucic S, Mathers S, Henderson R, Bellgard M, Aoun S, Savulescu J, Rowe D; $1,600,000
  • 2018-2022 NHMRC Program Grant: Frontotemporal Dementia and motor neurone degenerative syndromes; # APP1132524: $17,069,580; Chief Investigator


  • Dharmadasa, T., Howells, J., Matamala, J., Simon, N., Burke, D., Vucic, S., Kiernan, M.C. (2021). Cortical inexcitability defines an adverse clinical profile in amyotrophic lateral sclerosis. European Journal of Neurology, 28(1), 90-97.
  • Weiss, M., Macklin, E., McIlduff, C., Vucic, S., Wainger, B., Kiernan, M.C. et al (2021). Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial. Muscle and Nerve, 63(3), 371-383.
  • Kiernan, M.C., Vucic, S., Talbot, K., McDermott, C., Hardiman, O., Shefner, J., Al-Chalabi, A., Huynh, W., Cudkowicz, M., Talman, P., et al (2021). Improving clinical trial outcomes in amyotrophic lateral sclerosis. Nature Reviews Neurology, 17(2), 104-118.
  • Huynh, W., Tu, S., Mahoney, C., Schwartz, R., Kiernan, M.C. (2021). Mills Syndrome: Clinical and Radiologic Asymmetry. Neurology, 96(14), 677-678.
  • Agarwal, S., Highton-Williamson, E., Caga, J., Howells, J., Dharmadasa, T., Matamala, J., Ma, Y., Shibuya, K., Hodges, J., Ahmed, R., Vucic, S., Kiernan, M.C. (2021). Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis. Scientific Reports, 11(1), 2172.
  • Trinh, T., Park, S., Murray, J., Pickering, H., Lin, C., Martin, A., Friedlander, M., Kiernan, M.C., Goldstein, D., Krishnan, A. (2021). Neu-horizons: neuroprotection and therapeutic use of riluzole for the prevention of oxaliplatin-induced neuropathy a randomised controlled trial. Supportive Care in Cancer, 29(2), 1103-1110.
  • El-Wahsh, S., Finger, E., Piguet, O., Mok, V., Rohrer, J., Kiernan, M.C., Ahmed, R. (2021). Predictors of survival in frontotemporal lobar degeneration syndromes. Journal of Neurology, Neurosurgery and Psychiatry, 92(4), 425-433.
  • Caga, J., Zoing, M., Foxe, D., Ramsey, E., D'Mello, M., Mioshi, E., Ahmed, R., Kiernan, M.C., Piguet, O. (2021). Problem-focused coping underlying lower caregiver burden in ALS-FTD: implications for caregiver intervention. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Vucic, S.,
  • Kiernan, M.C.., Menon, P., Huynh, W., Rynders, A., Ho, K., Glanzman, R., Hotchkin, M. (2021). Study protocol of RESCUE-ALS: A Phase 2, randomised, double-blind, placebo-controlled study in early symptomatic amyotrophic lateral sclerosis patients to assess bioenergetic catalysis with CNM-Au8 as a mechanism to slow disease progression. BMJ Open, 11(1), e041479. [More Information]
  • De Boer, E., Orie, V., Williams, T., Baker, M., De Oliveira, H., Polvikoski, T., Silsby, M., Menon, P., van den Bos, M., Halliday, G., Kiernan, M.C., Vucic, S. (2021). TDP-43 proteinopathies: A new wave of neurodegenerative diseases. Journal of Neurology, Neurosurgery and Psychiatry, 92(1), 86-95.
  • Mahoney, C., Dharmadasa, T., Huynh, W., Halpern, J., Vucic, S., Mowat, D., Kiernan, M.C. (2020). A novel phenotype of hereditary spastic paraplegia type 7 associated with a compound heterozygous mutation in paraplegin. Muscle and Nerve, 62(1), E44-E45.
  • Shefner, J., Al-Chalabi, A., Baker, M., Cui, L., de Carvalho, M., Eisen, A., Großkreutz, J., Hardiman, O., Henderson, R., Matamala, J., Simon, N., Vucic, S., Burke, D., Kiernan, M.C. (2020). A proposal for new diagnostic criteria for ALS. Clinical Neurophysiology, 131(8), 1975-1978.
  • Vucic, S., Higashihara, M., Sobue, G., Atsuta, N., Doi, Y., Kuwabara, S., Kim, I., Kim, E., Talman, P., Menon, P., Kiernan, M.C. (2020). ALS is a multistep process in South Korean, Japanese, and Australian patients. Neurology, 94(15), E1657-E1663.