# Rheology biomarkers for gene-based therapy

> **NIH NIH OT2** · EMORY UNIVERSITY · 2020 · $354,458

## Abstract

Allogeneic hematopoietic stem cell transplant (alloHSCT) can provide a cure for sickle cell
disease (SCD), but is typically available only to the 10-15% of patients who have a matched
related donor. Fortunately, there are viable gene therapy (lentivirus based) and gene editing
(CRISPR/Cas9 based) approaches available in limited clinical trials. However, questions remain
regarding the level of sickle Hb (HbS) correction or fetal hemoglobin (HbF) induction and degree
of engraftment of gene modified stem cells needed to achieve a cure. Despite years of experience
with pharmacologic HbF induction with hydroxyurea (HU), and epidemiological studies of baseline
HbF levels and symptom correlation, it is not known what level of HbF is needed for significant
amelioration of SCD complications, or what %HbS can be tolerated when unequally distributed
throughout the red blood cells (RBCs).
It is essential that we functionally evaluate patients who have undergone gene-based therapy,
rather than rely solely on Hb profiles to assess response. The quality, or rheology, of SCD blood
is markedly abnormal, and these abnormalities correlate strongly with disease complications. The
goal of any gene-based SCD cure should be to normalize blood rheology of each patient to at
least the level of an individual with sickle cell trait (SCT). Non-curative therapies like HU and
transfusion relieve symptoms and improve rheology in patients with SCD, although not to the SCT
values. We propose to validate rheological biomarkers first in patients with SCD, testing the ability
of biomarkers to differentiate HbAA, HbAS, and HbSS samples. Next, we will assess the
biomarker performance in SCD patients who have undergone alloHSCT, asking if our biomarkers
predict an asymptomatic outcome consistent with a cure. Finally, we will apply these validated
biomarkers to patients treated with gene-based therapy. Strategies which do not achieve
rheological correction comparable to HbAS or successful alloHSCT may need further
optimization.

## Key facts

- **NIH application ID:** 10317537
- **Project number:** 7OT2HL155038-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Vivien Andrea Sheehan
- **Activity code:** OT2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,458
- **Award type:** 7
- **Project period:** 2020-03-23 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317537

## Citation

> US National Institutes of Health, RePORTER application 10317537, Rheology biomarkers for gene-based therapy (7OT2HL155038-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10317537. Licensed CC0.

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