Old drug provides promising new avenue for treatment of MND

May 17, 2018, University of Liverpool

An international study led by biochemists at the University of Liverpool has shown that the drug-molecule ebselen can correct many of the toxic characteristics of a protein that causes some cases of hereditary motor neurone disease (MND).

MND is an incurable, progressive disease that attacks the nerves controlling movement so muscles no longer work. MND affects about 5000 people in the UK at any one time and present treatment options have only a modest effect in improving the patient's quality of life.

Inherited MND is a rare form of the disease (5-10% of total cases) that runs in families. Around 20% of hereditary MND cases are caused by mutations in a gene which codes for a called SOD1. When the SOD1 gene is mutated, the protein assembly process malfunctions and steps are missed out. This makes the SOD1 protein structurally unstable leading to formation of protein 'clumps' in the neurones, causing them to die.

In a paper published in Nature Communications, scientists from the Universities of Liverpool (UK), Florence (Italy) and Wollongong (Australia) used state-of-the-art crystallography, mass-spectrometry and in-cell NMR technologies to search for a drug molecule which could 'correct' the SOD1 assembly line.

They found that ebselen, a drug which was discovered in the 1980s and has been investigated as a potential treatment for a variety of nervous system disorders, can effectively restore several important steps in the SOD1 assembly process including folding, dimerization and zinc binding.

Dr. Gareth Wright, an MND researcher at the University of Liverpool, said: "This discovery has the potential to prevent the accumulation of SOD1 into the large aggregates we see within the motor neurons of effected individuals. If we can stop that, we might be able to stop the neurons dying."

Professor Samar Hasnain, a structural biologist at the University of Liverpool, added: "The next step is to test ebselen in settings more accurately resembling human neuronal cells and optimising it so that it can become useful as a drug for ."

Commenting on the study, Dr Brian Dickie, Director of Research Development at the Motor Neurone Disease Association, said: "A causal link between the SOD1 gene and certain forms of hereditary motor neuron was established a quarter of a century ago. It is very encouraging to see new therapeutic strategies starting to emerge from the considerable advances in scientific understanding that have occurred in recent years."

Explore further: Large aggregates of ALS-causing protein might actually help brain cells

More information: Michael J. Capper et al, The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation, Nature Communications (2018). DOI: 10.1038/s41467-018-04114-x

Related Stories

Large aggregates of ALS-causing protein might actually help brain cells

April 16, 2018
Scientists at the UNC School of Medicine have made a significant advance in the understanding of the complex and fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.

Discovery may offer hope to Parkinson's disease patients

May 22, 2017
The finding of a common protein abnormality in these degenerative diseases supports a hypothesis among experts that abnormal deposition of proteins in many neurodegenerative disorders reflects an early change in these proteins.

Aggregated protein in nerve cells can cause ALS

May 4, 2016
Persons with the serious disorder ALS, can have a genetic mutation that causes the protein SOD1 to aggregate in motor neurons in the brain and spinal cord. Researchers at Umeå University have discovered that, when injected ...

Study highlights gene that could lead to therapies for Amyotrophic Lateral Sclerosis

October 4, 2016
Researchers from Ben-Gurion University of the Negev (BGU) have published a new study that describes a novel molecular mechanism that could lead to the development of new therapies for Amyotrophic Lateral Sclerosis (ALS). ...

New ALS discovery: Scientists reverse protein clumping involved in neurodegenerative conditions

September 22, 2016
In the quest to understand the driving forces behind neurodegenerative diseases, researchers in recent years have zeroed in on clumps of malfunctioning proteins thought to kill neurons in the brain and spinal cord by jamming ...

Recommended for you

Study of protein 'trafficker' provides insight into autism and other brain disorders

September 22, 2018
In the brain, as in business, connections are everything. To maintain cellular associates, the outer surface of a neuron, its membrane, must express particular proteins—proverbial hands that reach out and greet nearby cells. ...

Breast milk may be best for premature babies' brain development

September 21, 2018
Babies born before their due date show better brain development when fed breast milk rather than formula, a study has found.

Early warning sign of psychosis detected

September 21, 2018
Brains of people at risk of psychosis exhibit a pattern that can help predict whether they will go on to develop full-fledged schizophrenia, a new Yale-led study shows. The findings could help doctors begin early intervention ...

White matter repair and traumatic brain injury

September 20, 2018
Traumatic brain injury (TBI) is a leading cause of death and disability in the U.S., contributing to about 30 percent of all injury deaths, according to the CDC. TBI causes damage to both white and gray matter in the brain, ...

Gut branches of vagus nerve essential components of brain's reward and motivation system

September 20, 2018
A novel gut-to-brain neural circuit establishes the vagus nerve as an essential component of the brain system that regulates reward and motivation, according to research conducted at the Icahn School of Medicine at Mount ...

Genomic dark matter activity connects Parkinson's and psychiatric diseases

September 20, 2018
Dopamine neurons are located in the midbrain, but their tendril-like axons can branch far into the higher cortical areas, influencing how we move and how we feel. New genetic evidence has revealed that these specialized cells ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.