Theme 6 Tissue biomarkers

Area of Science:

• Neuroscience
• Metabolic Medicine
• Microbiome Research

Background:

• Glutamate excitotoxicity is a key hypothesis in Amyotrophic Lateral Sclerosis (ALS) pathophysiology.
• Elevated plasma glutamate levels in ALS patients suggest systemic defects in glutamate metabolism.
• Gut microbiota alterations and intestinal dysbiosis are increasingly implicated in ALS, potentially affecting glutamate homeostasis.

Purpose of the Study:

• To investigate plasma glutamate level fluctuations after protein consumption in ALS patients and family members.
• To assess the prevalence and severity of glutamate metabolism dysfunction (GMD) in ALS patients.
• To explore the relationship between GMD status and ALS progression.

Main Methods:

• Plasma amino acid analysis was performed pre- and post-protein shake consumption in 26 ALS patients and 10 family members.
• Glutamate Metabolism Dysfunction (GMD) was defined by post-prandial vs. fasting plasma glutamate level differences (>30 umol).
• A subset of ALS patients received a probiotic with high glutamine synthetase (GS) activity during a six-month treatment phase.

Main Results:

• 65.4% of ALS patients screened positive for GMD, compared to 30% of family members.
• ALS patients exhibited mild, moderate, and severe GMD, while family members showed only mild severity.
• Patients with stable/improving GMD saw slowed ALSFRS-R decline, while those with worsening GMD experienced faster progression.

Conclusions:

• This study is the first to investigate dietary glutamate metabolism impairment in ALS patients.
• Impaired glutamate metabolism dysfunction (GMD) is prevalent in ALS patients.
• GMD may serve as a novel biomarker and potential therapeutic target for ALS, warranting further investigation in larger cohorts.