In recent years, research has shown that physical exercise has many benefits for the entire body, beyond muscle growth. There has been much discussion in recent years about the value of physical activity programs in the case of Alzheimer's or Parkinson's disease.
Researchers at MIT wrote about experiments that might lend credence to the idea that mechanical stimulation could one day be beneficial in ALS or other MND diseases.
Muscles release various biochemical factors, called myokines, which circulate in the bloodstream. These molecules establish a kind of dialogue between different tissues and this allows them to collectively adapt to a new environment. Myokine receptors are found in muscle, fat, liver, pancreas, bone, heart, immune system and brain cells. The location of these receptors reflects the fact that myokines have multiple functions. First, they are involved in the metabolic changes associated with exercise, as well as in the metabolic changes that follow adaptation to training. To study these effects specifically on motor neurons, the cells that transmit movement commands from the brain to muscles, MIT researchers developed a series of in vitro systems where they could precisely control and observe the effects of muscle contractions.
In 2023, Raman and his colleagues reported that they could restore mobility in mice that had suffered traumatic muscle injury by first implanting muscle tissue at the site of the injury and then exercising the new tissue by repeatedly stimulating it with light. Over time, they found that the exercised graft helped the mice regain motor function, reaching levels of activity comparable to those of healthy mice. This meant not only that the new muscle tissue had become functional, but also that there were somehow new connections between the lower motor neurons and the new muscles. In other words, the exercise was not only beneficial for the new muscle but also for the local motor neuron that develops synapses to connect to muscle fibers.
Then the group wondered: Could exercise’s purely physical impacts have a similar benefit on motor neurons?
This claim was met with some skepticism.
So the MIT team designed experiments in which the neurons were repeatedly pulled back and forth, similar to the way muscles contract and expand during exercise.
Angel Bu is the first author, while Ritu Raman is the senior author; the other authors are from MIT’s Department of Mechanical Engineering and MIT’s Koch Institute for Integrative Cancer Research. The authors matured a set of motor neurons on a gel that was a kind of carpet into which they embedded tiny magnets. They then used an external magnet to shake the carpet—and the neurons—back and forth. In this way, they made the neurons work, for 30 minutes a day.
The researchers demonstrated that the physical force generated during muscle contraction has direct mechanical effects on motor neurons, promoting growth in both a biochemical and mechanical way. And the two effects, myokine release and motor neuron work, have similar effects.
These results could have important implications for the treatment of motor neuron diseases, such as amyotrophic lateral sclerosis (ALS) or spinal muscular atrophy, where motor neurons progressively lose their function. Therapies that mechanically stimulate muscle contractions could encourage nerve growth and regeneration, potentially slowing the progression of these diseases or facilitating recovery after nerve damage.
Of course, this study is extremely preliminary, it is carried out in vitro. We cannot even talk about micro-organs. This is basic research indeed, the authors didn't talk about applications in ALS/MND diseases. Another limitation of this study is that the authors did not explore a wide variety of mechanical or biochemical stimulation protocols with different frequencies, magnitudes, and durations.
If these mechanisms were confirmed in preclinical studies with primates and then clinical studies with humans, exercise protocols could be refined to maximize the biochemical and mechanical benefits for motor neurons, potentially improving motor function or slowing disease progression in patients with motor neuron diseases.
For example, patients could benefit from muscle stimulation devices that could help maintain or even regenerate motor neuron pathways. Mechanical muscle stimulation could indeed be a way to mimic the combined biochemical and mechanical effects of muscle contractions in patients with weakened muscles, potentially helping to slow neuronal degeneration or even stimulate nerve repair.
Electrical stimulators already exist for physiotherapy and rehabilitation, and future protocols could incorporate fine-tuning to produce exercise-like contractions that not only provide muscle benefits but also encourage motor neuron activity. Given that MND patients vary greatly in progression and severity, personalized electrical stimulation programs would be essential. Clinicians could develop individualized regimens, perhaps informed by biomarkers or real-time feedback, to maximize neuron growth-promoting effects without overloading the system.
Future research could test whether electrical muscle stimulation in MND patients produces benefits similar to biochemical and mechanical stimulation observed in vitro. If effective, this could lead to new physiotherapy protocols or devices aimed at improving the quality of life and motor function of people with MND.
