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Plasma Factors in Patients with Sickle Cell Disease

Advancing understanding of the factors causing pain in patients with Sickle Cell Disease to identify targets for therapeutic intervention

Full Project Name:Plasma Factors in Patients with Sickle Cell Disease Sensitize Nociceptors to Drive PainPrincipal Investigator:Cheryl L. Stucky, PhD, Cell Biology, Neurobiology, and AnatomyCo-Investigator:Amanda M. Brandow, DO, MS, Pediatrics; Allison D. Ebert, PhD, Cell Biology, Neurobiology, and AnatomyAward Amount:$250,000
Award Date
July2021
Project Duration:24 months

Project Description Narrative:


Sickle Cell Disease (SCD) is the most common inherited hemoglobinopathy in the United States, affecting over 100,000 individuals who are primarily Black and Hispanic. SCD leads to restricted blood flow, severe pain, and chronic inflammation. Collectively, this leads to multi-organ damage and premature death. Acute severe pain is the most common cause of hospitalization in patients with SCD, costing $2 billion per year in the U.S. and equating to approximately $20 million per year in Wisconsin, where an estimated 1,000 children and adults have SCD.

FDA-approved treatments for SCD decrease the frequency of occurrence of acute pain episodes. However, treatment options mainly rely on opioids, which fail to completely alleviate pain and have serious adverse side effects. Coupled with systemic racial discrimination in health care, patients in desperate need of pain relief are less likely to have their pain treated. These treatment discrepancies and the current opioid crisis create an immediate need for non-opioid-based SCD pain therapies. However, in order to develop novel therapies, a better understanding of the biological mechanisms underlying human SCD pain is needed.

Through this award, investigators aim to advance understanding of the factors that cause pain in SCD patients in order to help identify targets for therapeutic intervention.

Project Updates:


  • Identified potential intrinsic mechanisms of SCD pain which may extend beyond a blood-based disease pathology
  • Reproduced results that suggest that iSNs (induced pluripotent sensory neurons) derived from patient iPSCs (induced pluripotent stem cells) can be used in parallel with native SCD neurons from mouse models to investigate mechanisms underlying the chronic sensory neuron sensitization in SCD
  • Performed in depth metabolomics analyses of plasma from 6 SCD individuals in acute pain and currently analyzing data
  • Gathered preliminary data to contribute to an NIH R01 application

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