Newly Identfied Genetic Variants in MND Support Prognosis and Family Testing

Motor neuron disease (MND) is a neurodegenerative condition in which the nerves controlling movement fail, leading to progressive paralysis and early death, often about two years after diagnosis. Clinicians have limited tools to predict prognosis and guide family counseling. An international analysis of rare genetic variants now aims to define the genetic contribution to MND more precisely. The work seeks to expand the evidence base for patient management and development of targeted therapies.

Project MinE, an international consortium co-founded by researchers at King’s College London, led the effort alongside the University of Utrecht. The study was published in Nature Genetics on March 31, 2026. King’s College Hospital NHS Foundation Trust contributed samples through the UK MND DNA Bank, a project led by King’s College London.

Image: The findings inform MND care by linking variants to prognosis and highlighting inherited mutations that support family genetic testing (photo credit: Adobe Stock)

Investigators analyzed DNA from more than 18,000 people with MND, including 2,000 samples from the UK MND DNA Bank. The analysis identified additional rare variants linked to disease risk and established that 25% of patients carry a genetic change related to their MND, irrespective of family history. This raises earlier estimates of identifiable genetic contribution from one in five to one in four and reinforces the central role of genetics in disease development.

The unprecedented scale of the dataset enabled discovery of rare variants that smaller studies could not detect. Prior research tended to examine mutations segregating within families or common variants in unrelated individuals. By aggregating exome data across a large population, researchers were able to uncover previously unknown, population-level rare mutations.

The findings have direct relevance for clinical care. Specific variants can inform management decisions because some variants influence prognosis. Newly identified mutations may be inherited, making them pertinent to relatives and supporting integration of family genetic testing into care plans. The discoveries may also guide the long-term development of targeted treatments.

The findings are also relevant in the therapeutic context where options remains limited for most patients. In 2022, tofersen became the first therapy to address a genetic form of MND by targeting variants in the SOD1 gene. In the United Kingdom, this applies to about 2% of patients. The newly discovered genes provide additional potential targets for similar approaches as the therapeutic landscape evolves.