- In a study funded in part by the Muscular Dystrophy Association, treatment with a small molecule called trehalose slowed disease progression and extended life span in mice with a disease mimicking amyotrophic lateral sclerosis.
- Trehalose treatment in the mice was associated with decreased levels of toxic SOD1 protein, reduced activation of potentially toxic cells called astrocytes, and increased survival of nerve cells.
- Study findings suggest that the protective effects associated with trehalose treatment in the mice may have been the result of increased activation of a cellular waste disposal process called autophagy.
- The researchers suggest that therapies designed to enhance autophagy may be beneficial in ALS.
Treatment with a small molecule called trehalose was associated with slower disease progression and longer life span in mice with a disease mimicking amyotrophic lateral sclerosis (ALS), an MDA-supported research team has reported.
Trehalose is a type of sugar composed of two glucose molecules.
Claudio Hetz at the University of Chile in Santiago, and colleagues, reported that the protective properties associated with trehalose treatment in the mice may have been the result of upregulation (increased activity) of a cellular cleanup and garbage-disposal process called autophagy (“awe-TOF-uh-gee”). Disruption of the autophagy process in ALS has been associated with abnormalities of the SQSTM1 and ubiquilin 2 (UBQLN2) genes and proteins.
The findings were published online June 6, 2013, in Autophagy (see Trehalose Delays the Progression of Amyotrophic Lateral Sclerosis by Enhancing Autophagy in Motor Neurons; the entire paper is available with a subscription or one-time fee). MDA supported Hetz for his work on this project.
Note: Although trehalose may be purchased in the United States, its effects in people with ALS are unknown. Therefore, individuals are strongly advised not to use it to treat ALS until it has been proven safe and effective in people with the disease. Always consult with your physician before making any changes to your treatment plan.
Trehalose increased nerve-cell survival
SOD1 ALS research mice, which are engineered to have an ALS-like disease caused by mutations in the superoxide dismutase 1 (SOD1) gene, received intraperitoneal injections of trehalose three times per week and consumed additional small quantities of the compound in their drinking water.
When compared to mice that were treated with molecules similar to trehalose, or an inactive solution (placebo), the trehalose-treated mice had a significant extension of life span. The effect was stronger in male mice, which lived about 22 percent longer (32 days) than untreated male mice (placebo group). Female mice lived approximately 11 percent longer (15 days) than untreated female mice.
The trehalose-treated mice also had a slower progression of disease symptoms than untreated mice; no gender differences were reported on this measure.
The researchers reported that the observed effects in the mice were associated with:
- decreased levels of toxic SOD1 protein in the brain and spinal cord;
- reduced activation of nervous system cells called astrocytes, which normally protect other cells but can also turn against them; and
- increased survival of motor neurons, the muscle-controlling nerve cells that are lost in ALS.
Trehalose may have enhanced autophagy
Trehalose treatment in the mice induced a significant increase in levels of biological markers associated with the cellular waste disposal system known as autophagy. In addition, the activity of genes associated with autophagy, including SQSTM1, was increased in the treated mice.
Although it's unclear how trehalose may stimulate autophagy, the researchers noted that the protective properties associated with trehalose treatment in the ALS mice appear to have been caused by increased activation of the autophagy process in motor neurons.
The study findings support the investigation of potential ALS therapies based on enhancement of the autophagy process.