Lower levels of two molecules linked to faster ALS progression, shorter survival
Study findings may provide foundation for development of new treatments
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- Lower adiponectin and IL-10 levels are linked to faster ALS progression and shorter survival.
- These molecules may serve as biomarkers for ALS prognosis and guide new treatment development.
- Initial scores on the ALS Functional Rating Scale-Revised were independently associated with survival.
Lower blood levels of adiponectin, a signaling molecule produced by fat tissue, and the anti-inflammatory molecule interleukin (IL)-10 are associated with faster disease progression and shorter survival in people with amyotrophic lateral sclerosis (ALS), a study in China found.
The findings also showed that established prognostic measures, such as the initial scores on the ALS Functional Rating Scale-Revised (ALSFRS-R), a well-known measure of physical function, and the rate of disease progression were independently associated with survival.
“These findings provide a robust theoretical foundation for the development of new treatment strategies and strong biomarker support for assessing the prognosis of ALS patients in clinical settings,” researchers wrote in the study, “The role of adiponectin and cytokines in Amyotrophic lateral sclerosis: assessment of disease progression and survival status,” which was published in Scientific Reports.
Molecules may potentially serve as useful biomarkers in ALS
Inflammation is believed to play a key role in neurodegenerative conditions, with previous research showing that many inflammatory markers are associated with ALS progression and survival.
Fat tissue releases signaling proteins, called adipokines, that also help regulate metabolism and inflammation, and growing evidence suggests these molecules may contribute to inflammation and potentially serve as useful biomarkers in ALS.
One adipokine of interest is adiponectin, which has anti-inflammatory properties and has been linked to neurodegenerative conditions. However, its role in ALS remains poorly understood.
In this study, a team of researchers in China examined whether adiponectin and other inflammatory signaling molecules produced by immune cells were associated with disease progression and survival in people with ALS.
The study included 80 ALS patients treated at the Second Hospital of Hebei Medical University between February 2023 and April 2024. Patients were classified as having slow or fast disease progression based on the monthly decline in their ALSFRS-R scores. A decline of at least one point per month was considered rapid progression.
Results showed that patients with rapidly progressing disease had significantly lower levels of adiponectin and IL-10 compared with slow progressors. They also had higher levels of several pro-inflammatory molecules, including IL-1 beta, IL-2, IL-6, IL-8, and TNF-alpha.
Researchers identify 5 factors associated with survival
The researchers then analyzed how the various molecules related to disease severity and progression. Data showed that higher levels of pro-inflammatory molecules were associated with worse functional status and faster disease progression after 1.5 years of follow-up, while higher adiponectin and IL-10 levels were linked to better function and slower progression.
By the end of follow-up, 33 patients (41.2%) had died. Compared with survivors, these patients had significantly lower adiponectin levels and IL-10 levels, as well as higher levels of several inflammatory markers, and of FGF-21, another adipokine.
The researchers then used more advanced statistical analyses to identify the factors most strongly associated with survival. This narrowed the list to five factors: initial ALSFRS-R score, rate of ALSFRS-R decline, adiponectin, IL-6, and IL-10.
Further analyses accounting for age, sex, and initial symptoms showed that higher adiponectin and IL-10 levels, along with higher ALSFRS-R scores, were associated with longer survival. Faster disease progression, in turn, was associated with a greater risk of death.
The researchers noted that adiponectin may influence ALS through several mechanisms, including regulating inflammation, insulin sensitivity, and muscle function.
“Combining adiponectin and IL-10 with established central nervous system derived biomarkers … is expected to optimize prognostic models and aid in clinical trial stratification and personalized treatment strategies,” they concluded.
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