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Related Experiment Video

Updated: Jul 14, 2026

Simplified Intrafemoral Injections Using Live Mice Allow for Continuous Bone Marrow Analysis
06:28

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Published on: November 10, 2023

GBT-1118 Rescued Impaired Bone Formation but Failed to Rescue Material Properties in Humanized Sickle-Cell-Disease

Kai Clarke1, Wei He1, Nikhil Menon2

  • 1Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, UConn Health, Farmington, CT 06032, USA.

Cells
|July 13, 2026
PubMed
Summary

Sickle cell disease (SCD) treatment with GBT1118 improved anemia in mice but did not restore impaired bone material or mechanical properties. Further therapies are needed for bone fragility in SCD.

Keywords:
bone diseasehemoglobin allosteric modifiermaterial testingmechanical testingsickle cell diseasevoxelotor analog GBT1118

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Area of Science:

  • Hematology
  • Orthopedics
  • Pharmacology

Background:

  • Sickle cell disease (SCD) is a common inherited blood disorder with bone loss complications similar to osteoporosis.
  • GBT1118, a sickle hemoglobin polymerization inhibitor, previously improved bone formation and reduced resorption in SCD mice.
  • The effects of GBT1118 on bone material and mechanical properties in SCD were previously unknown.

Purpose of the Study:

  • To investigate the impact of GBT1118 on bone material and mechanical properties in a mouse model of sickle cell disease.

Main Methods:

  • Control and SCD mice were administered GBT1118 or vehicle for two months.
  • Hematocrit levels were measured to assess anemia.
  • Raman spectroscopy and mechanical testing were used to evaluate bone material and properties.

Main Results:

  • GBT1118 treatment restored hematocrit levels in SCD mice, indicating efficacy against anemia.
  • Bone mineral-to-organic matrix and carbonate-to-phosphate ratios were altered in SCD mice but not by GBT1118.
  • Female SCD mice showed decreased ultimate stress and Young's modulus, which GBT1118 did not rescue.

Conclusions:

  • While GBT1118 effectively improved hematological parameters in SCD mice, it did not restore impaired bone material or mechanical properties.
  • Additional therapeutic strategies are necessary to address bone fragility in sickle cell disease.