C9orf72 cohort study

A study to characterise C9orf72 patients and asymptomatic carriers

UK Chief Investigator

Professor Kevin Talbot

Research summary

The purpose of this study is to investigate possible causes of nerve damage in patients carrying a genetic abnormality in the gene C9orf72. The abnormality in the C9orf72 gene is known to cause amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), and the related condition frontotemporal dementia (FTD).

To carry out the study, we need to obtain blood and other biological samples from carriers of the C9orf72 gene abnormality who have ALS or FTD, as well as their family members who do not have ALS or FTD symptoms. Identification of why patients carrying the abnormality develop ALS and FTD may help us in the future to find treatments to help prevent these conditions.

The C9orf72 abnormality is the most common genetic cause of ALS and FTD and is present from birth in patients who carry it.

By studying biological samples from patients and relatives, we can gain an understanding of the processes that are at work in this inherited form of ALS and FTD. Samples from blood and the fluid that surrounds the brain as well as brain imaging and electrical nerve tests, provide a window into the changes that are driving the disease at a molecular level. This will help us to increase our understanding of the biological markers that are relevant to the mutation and better monitor response to treatments during future trials.

Eventually, all of this knowledge may contribute towards the development of new treatments for the C9orf72 gene mutation and ALS and FTD in general.

Inclusion / exclusion criteria

Inclusion criteria

For all participants:

  • Aged 18 and over.

  • Participant is willing and able to give informed consent for participation in the study, or an appropriate consultee can be identified to provide advice about his/her friend or relative’s inclusion in the study.

  • If the participant is unable to provide written consent due to physical disability, an independent witness will be present at the informed consent discussion and sign the consent form on the participant's behalf.

Additional criterion for patients with ALS:

Diagnosis made by experienced neurologist.

Additional criterion for patients with FTD:

Diagnosis made by experienced neurologist or psychiatrist.

Additional criterion for family members:

Known to have C9orf72 HRE mutation, or is a first or second-degree genetic relative of a C9orf72 positive ALS or FTD patient.

Additional criterion for healthy volunteers:

No family history of MND or FTD

Exclusion criteria

The participant may not enter the study if ANY of the following apply:

  • Under 18 years of age.

  • Pregnancy or any other condition that in the opinion of the investigator could interfere with the interpretation of the study results.

In addition to the general inclusion / exclusion criteria described above, the additional exclusion criteria apply for invasive procedures (skin biopsy and lumbar puncture):

Significant bleeding diathesis or sepsis, or other condition that in the opinion of the investigator could constitute a health risk to the participant if he/she took part in this element of the study.

In addition to the general inclusion/exclusion criteria described above, the additional exclusion criteria apply for imaging procedures (MRI):

  • Significant orthopnea or secretions, defined as subjectively intolerable breathlessness on lying flat or oxygen saturations below 90% on lying flat for 10 minutes.

  • Severe physical disability that might preclude accessing the scanner or prevent communication of any distress during testing or presence of any incompatible (or possibly incompatible) metal implants or large tattoos suspected to contain iron pigments.

In addition to the general inclusion / exclusion criteria described above, the additional exclusion criteria apply for non-invasive EMG:

An implantable cardioverter-defibrillator (ICD) device.

Current status

Active – Recruiting


Main site: Oxford

Participant identification centres (invite participants to take part and refer those interested to the main site):

  • Basingstoke and North Hampshire Hospital

  • St Mary's Hospital, Isle of Wight NHS Trust

  • Poole General Hospital

  • Queen Alexandra Hospital, Portsmouth Hospitals NHS Foundation Trust

  • Salisbury District Hospital

  • Western Community Hospital, Solent NHS Trust

  • Royal Bournemouth General Hospital

  • Southampton General Hospital

Information about study sites

Contact details

Lead site: Emma Harper

Email: emma.harper@ndcn.ox.ac.uk

Recruitment group(s)

  1. Patients with ALS or FTD carrying the C9orf72 HRE (ALS/FTD patients).

  2. Patients with sporadic forms of ALS/FTD.

  3. Family members of patients carrying the C9orf72 HRE who may or may not be aware of their genetic status.

  4. Healthy volunteers with no family history of ALS or FTD.

Recruitment target(s)

  • 100 ALS/FTD patients

  • 100 family members

  • 50 healthy volunteers

  • 50 patients with sporadic ALS/FTD

Key dates

Actual opening date: 5 March 2019

Recruitment planned end date: 30 June 2022


  • Association of British Neurologists (ABN) Clinical Research Training Fellowship fund

  • Motor Neurone Disease Association (MNDA)


University of Oxford

Study design

Cross-sectional observational

Intervention (if applicable)

Not applicable

Phase (if applicable)

Not applicable

Outcome measures

Clinical, biomarker and radiological characterisation of C9orf72 patients and asymptomatic carriers. Clinical database with multi-modal phenotyping data.

Publications / Results reports

Links will be provided when papers are published.