Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is the most common form of motor neuron disease. People with ALS gradually lose the ability to initiate and control muscle movements, including the ability to speak, swallow, and breathe.
There is no known cure. But recently, we studied mice and identified a new goal in the fight against this devastating disease: the brain waste disposal system.
Neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s and multiple sclerosis, share many similarities, although their clinical symptoms and disease progression may appear very different. The incidence of these diseases increases with age. They are progressive and relentless, and cause a gradual loss of brain tissue. We also see that waste proteins build up in the brain.
Our new research looked at how the lymphatic system, which removes waste from the brain, could prevent ALS.
Read more: ALS is only 50% genetic: Identifying DNA regions affected by lifestyle and environmental risk factors could help identify treatment pathways
Protein chains, folds and folds
Inside our bodies, long chains of proteins fold to form functional forms that allow them to perform specific tasks such as creating antibodies to fight infection, support cells, or transport molecules.
Sometimes this process goes wrong, resulting in “unfolded” proteins that clump together to form aggregates. Poorly folded protein can grow and fragment, creating seeds that spread throughout the brain to form new groups.
The accumulation of waste proteins begins early in the process of neurodegenerative disease, long before the onset of symptoms and brain loss. As researchers, we wanted to see if eliminating or slowing the spread of these waste proteins and their seeds could stop or slow the progression of the disease.
Guidance on waste removal
The lymphatic system removes waste, including toxic proteins, from the brain.
This cerebral network of fluid-filled spaces, known as Virchow-Robin spaces, goes out mostly while we are awake. But it is set in motion during sleep to distribute compounds that are essential for the functioning of the brain and to get rid of toxic waste.
This may explain why all creatures, large and small (even flies), need sleep to survive. (Interestingly, whales and dolphins alternate their sleep between the cerebral hemispheres, keeping the other hemisphere awake to watch for predators and alerting them to breathe!)
Unlike us, dolphins sleep with one side of their brain at a time. Unsplash / NOAA, CC BY
As we age, sleep quality decreases and the risk of developing neurodegenerative diseases, including ALS, increases.
Sleep disorders are also a common symptom of ALS, and research has shown that a single sleepless night can lead to a greater accumulation of toxic waste proteins in the brain. As such, we thought that lymphatic function could be impaired in ALS.
Read more: Longer naps a day can be an early sign of dementia in older adults
Aged mice
To investigate this, we looked at the mice. The animals were genetically modified to express human TDP-43, the protein involved in ALS. By feeding these mice food that contained an antibiotic (doxycycline), we were able to turn off TDP-43 protein expression and they would age normally. But when mice switch to normal food, TDP-43 expression is activated and poorly folded proteins begin to accumulate.
Over time, mice show classic signs of ALS, such as progressive muscle damage and brain atrophy.
Using magnetic resonance imaging (MRI) to see the structure of the brain, we investigated the lymphatic function in these mice just three weeks after activating TDP-43 expression.
While we saw that the lymphatic system was working, we saw that TDP-43 mice had worse lymphatic elimination than control mice that had not been genetically modified. It is important to note that these differences were observed very early in the disease process.
Our study provides the first evidence that the lymphatic system could be a potential therapeutic target in the treatment of ALS.
How can we improve our lymphatic function?
Not all sounds are the same. Sleep includes both rapid eye movement (REM) and non-REM sleep. This last stage includes the sleep of slow waves, when the glymphatic system is more active. Sleep therapies that improve this phase can be especially beneficial in preventing diseases such as ALS.
It is also believed that the sleeping position affects the cleansing of the lymph.
Research on rodents has shown that the removal of the lymphatics is more efficient in the lateral (or side) position, compared to the supine (back) or prone (front) positions. The reasons for this are not yet fully understood, but are possibly related to the effects of gravity, compression, and tissue stretching.
Read more: “Sleeping in” helps you better manage your emotions and mental health; here’s why
Lifestyle options can also be helpful in improving your lymph function. Omega-3, found in fish of marine origin, has long been considered beneficial to health and reduces the risk of neurodegenerative diseases. New research shows that these benefits may be due in part to the positive effect of Omega-3 on lymphatic function.
Moderate alcohol consumption has been shown to improve waste disposal. In studies with mice, short- and long-term exposure to small amounts of alcohol was shown to increase lymphatic function while high doses had the opposite effect.
Exercise has also been shown to be beneficial.
All of these studies show that small lifestyle changes can improve the elimination of brain waste to minimize the risk of developing neurodegenerative diseases. Next, research should focus on therapies aimed directly at the lymphatic system to help those already suffering from these debilitating diseases.