Super-activation of vitamin A signaling system protects against motor neuron disease, other conditions

Drugs that “switch on” vitamin A in the body may also help stave off conditions such as motor neuron disease (MND).

New research from the University of Aberdeen published today in Frontiers in Neuroscience, found, for the first time, that drugs that target the specific receptors necessary to activate vitamin A may be therapeutic for diseases that lead to deterioration of the brain.

Specifically, when disease conditions were simulated in the laboratory, the team found that super-activation of the vitamin A signaling system helped protect against the type of damage that can occur in diseases such as MND.

Professor Peter McCaffery, Chair in Medical Sciences at the University of Aberdeen, who led the study, explains, “We discovered that these drugs bind and turn on the ‘retinoic acid receptor,’ a key protein involved in activation of vitamin A in the body.”

Azita Kouchmeshky, neuroscientist at the University of California, San Francisco, and first author, said, “We tested these drugs in a series of studies on neurons grown in a dish. Chemicals were added to the neurons that caused harm similar to the changes that occur in diseases such as MND or ALS.

“Usually, these chemicals will cause the neurons to die. However, the application of the drugs that bind to the retinoic acid receptor significantly reduced the number of cells that died off.

“The same drugs were also tested in mice and were found to induce changes that suggest they may also be effective in the body.”

Motor neuron disease affects 5,000 adults in the U.K. at any one time and there is a 1 in 300 risk of getting MND across a lifetime. Once the disease progresses, it leads to the death of the motor neurons essential for muscle control, resulting in progressive muscle weakness, and in most cases the disease is fatal in a few years. No treatments currently exist that will improve this condition for more than just a few months.

Professor McCaffery is hopeful that this discovery can lead to new treatments for MND. He said, “Our research provides the first steps to identify new targets for drugs that may then lead to future therapies.”

Collaborator on the project, Andy Whiting, CEO of Nevrargenics Ltd and emeritus professor at Durham University designed and synthesized the drugs the team used.

Professor Whiting said, “There is a total lack of genuinely disease modifying drugs out there for neurodegeneration in general, and ALS specifically. We are committed to changing that and delivering hope for MND sufferers in the first instance. This is one further step along the road to deliver new therapeutics for such globally challenging diseases.”

Dr. Nicholas Cole, head of research at the MND Association said, “We are delighted to be supporting such valuable early work which we hope will go towards aiding the discovery of potential new therapies which could be put forward for clinical testing.

“The hope, of course, is that through continuing public support, collaboration and partnership working, we will find solutions to unpick the complex nature of MND, which will lead to an effective treatment.”