MND genetics

Next generation genetic screening in motor neuron disease

UK Chief Investigator

Dr Pietro Fratta

Research summary

Motor neuron diseases (MND) are a group of progressive incurable neurodegenerative disorders. A number of genetic defects have been identified as causative for MND although the cause of the majority of cases is still unknown.

The only drug shown to modify disease course is riluzole, which has a significant, but modest effect of prolonging survival of two to three months (Miller et al. 2012). Novel therapeutic strategies are currently aiming at targeting the primary genetic defects that cause MND, making rapid and efficient genetic screening crucial for future therapeutic strategies.

We propose to genetically screen 200 participants with a suspected, possible, probable or definite diagnosis of ALS or diagnosed with other MND variants, and blood related family members in a rapid and effective way. This process will be fully integrated with the clinical diagnostic laboratory at the NHNN. This program will benefit both patients and clinical research.

The benefits this program will bring to MND patient care in the NHS and to MND research are:

  1. Set the foundation for an effective rapid genetic screening in the UK that will facilitate trials for gene-specific therapeutic approaches.

  2. Provide a comprehensive research genetic report that can, following targeted validation, be communicated to patients who wish to receive feedback from the genetic screening.

  3. Recruit patients for specific research studies, based on their genetic stratification.

  4. Apply genetic findings to all research results from collected biosamples in ongoing biomarker studies (blood, CSF, fibroblasts).

  5. Allow researchers to focus further more costly genetic research on a smaller selected number of samples.

  6. Guarantee diagnostic standards for extraction and storage of patient DNAs, for future use of patients themselves or family members for diagnostic purposes.

Inclusion / exclusion criteria

Inclusion criteria

  • Diagnosis of suspected, possible, probable or definite ALS according to the El Escorial Criteria (Ross et al. 2001).

  • Other MND patients and patients affected by related conditions, including individuals affected by

    • progressive bulbar palsy (PBP)

    • primary lateral sclerosis (PLS)

    • progressive muscular atrophy (PMA)

    • spinal bulbar muscular atrophy (SBMA or Kennedy's disease)

    • adult onset spinal muscular atrophy (SMA)

    • hereditary spastic paraparesis (HSP)

    • multisystem proteinopathy (MSP)

    • frontotemporal dementia (FTD)

  • Individuals with a confirmed diagnosis of MND currently on treatment with disease-modifying treatments.

  • Patients over 18 years of age.

  • Control groups will include: Family members of MND patients over 18 years of age.

Exclusion criteria

Patients from the above described groups and family members below 18 years of age or who are unable to consent.

Current status

Active – recruiting

Locations

London (UCL/National Hospital for Neurology and Neurosurgery)

Information about study sites

Contact details

Luca Zampedri

Email: luca.zampedri@nhs.net

Recruitment group(s)

  • Patients with MND

  • Family members of patients with MND

Recruitment target(s)

150 patients and 50 healthy family members

Key dates

Actual opening date: 28 September 2018

Recruitment planned end date: 14 July 2023

Funder(s)

NIHR Clinician Scientist Award Scheme

Sponsor

University College London

Study design

Observational (genetic epidemiology)

Intervention (if applicable)

Not applicable

Phase (if applicable)

Not applicable

Outcome measures

The principal objective of this project is to identify genetic variations causative for MND in our cohort of patients.

Secondary objectives:

  • To set the foundation for an effective rapid genetic screening in the UK that will facilitate trials for gene-specific therapeutic approaches.

  • To provide a comprehensive research genetic report that can, following targeted validation, be communicated to patients who wish to receive feedback from the genetic screening.

  • To apply genetic findings to all research results from collected biosamples in ongoing biomarker studies (blood, CSF, fibroblasts).

Publications / Results reports

Links will be provided when papers are published.