Improved mobility and balance observed in mice with AS due to linoleic acid

A groundbreaking study led by Dr. Matthias Schweizer and his team has discovered a potential treatment for movement and balance problems in Angelman Syndrome (AS). The research, published in the journal Nature Communications, focuses on the enhancement of a protein channel called PIEZO2, found in nerve cell membranes, through a diet rich in linoleic acid.

AS is a genetic disorder that results in a missing or malfunctioning UBE3A enzyme, which helps maintain the balance of protein in neurons in the brain. This deficiency leads to a range of symptoms, including ataxic gait and poor balance.

The study found enhanced activity of PIEZO2 in AS mice fed a linoleic acid-enriched diet. Interestingly, normal mice fed the same diet also showed increased PIEZO2 activity. DRGs, sensory neurons that participate in proprioception, the sense of body movement and position, were found to be particularly responsive to this diet.

The findings provide a proof of concept that increasing dietary linoleic acid may be a viable treatment for the movement and balance problems associated with AS. In the mouse model of AS, feeding the mice a linoleic acid-enriched diet restored their stride length and number of steps to levels seen in healthy mice.

PIEZO2 is known to help mediate coordination and balance, and its enhanced activity may be a therapeutic target for AS. Initial experiments confirmed that DRG neurons from mice deficient in UBE3A had reduced PIEZO2 activity. Moreover, PIEZO2 deficiency in humans and mouse models impairs proprioception, leading to sensory ataxia.

Similar findings were observed in human Merkel cells, sensory neurons in the skin that also produce PIEZO2 and respond to physical touch. The linoleic acid diet did not affect body weight, showed no immune activation, and did not enhance nociception in mice, suggesting that the benefits are specific to improving proprioception.

It's worth noting that a lack of UBE3A in the cerebellum does not fully explain the ataxic gait and poor balance seen in AS. This suggests that other factors may also contribute to the symptoms of AS. However, the discovery of the role of PIEZO2 in this context opens up new avenues for research and potential treatments.

In conclusion, the study offers promising results for the treatment of movement and balance problems in AS. Further research is needed to confirm these findings in human trials and to fully understand the mechanisms at play. However, the potential of a linoleic acid-enriched diet as a treatment for AS is an exciting development in the field.