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Metformin Repurposing in Neurological Disorders: A Clinical Trial Landscape.

Yukesh R1, Sushil Sharma1, Madhavrao C1

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Metformin shows promise for treating central nervous system (CNS) disorders by activating pathways that protect nerves and promote repair. Further research is needed to confirm its effectiveness as a disease-modifying therapy.

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Area of Science:

  • Neuroscience and Pharmacology
  • Drug Repurposing
  • Clinical Trial Analysis

Background:

  • Neurological disorders like Alzheimer's disease and multiple sclerosis cause nerve cell loss, with current treatments offering only symptomatic relief.
  • Drug repurposing, particularly of metformin, is being explored for central nervous system (CNS) disorders due to its neuroprotective and remyelinating potential.
  • Metformin's mechanism involves activating the adenosine monophosphate-activated protein kinase (AMPK) pathway.

Purpose of the Study:

  • To systematically analyze the current clinical trial landscape for metformin repurposing in CNS disorders.
  • To identify the range of neurological, neurodegenerative, and neurodevelopmental conditions being investigated.
  • To understand the therapeutic goals and outcome measures used in these trials.

Main Methods:

  • Data was exclusively sourced from ClinicalTrials.gov.
  • A focused search included neurological, neurodegenerative, and neurodevelopmental conditions, excluding trials primarily for type 2 diabetes or cancer.
  • 23 clinical studies were selected, with data extracted on disease types, therapeutic aims, and measurable outcomes.

Main Results:

  • Research on metformin in CNS disorders is active, with many trials completed or recruiting.
  • Multiple sclerosis (MS), schizophrenia/psychosis, and fragile X syndrome (FXS) are key areas of investigation.
  • Trials utilize functional assessments (e.g., T25FWT, MCCB) and biomarkers (e.g., DTI, NfL, GFAP) to measure treatment effects.

Conclusions:

  • There is increasing interest in repurposing metformin for CNS disorders, focusing on neurorepair.
  • Biomarker-based assessments are becoming standard in evaluating metformin's efficacy.
  • Larger, well-designed randomized controlled trials are essential to confirm metformin's therapeutic benefits in humans.