Credit: Graham Colm
MIAMI—Results of a small study suggest an experimental agent can decrease the erythrocyte sedimentation rate (ESR) in patients with sickle cell disease (SCD).
Previous research has shown the ESR is elevated in SCD patients during vaso-occlusive crisis.
In the current study, the experimental agent MST-188 decreased elevated ESRs by 50% in blood from SCD patients.
According to researchers, this reflects reduced red blood cell (RBC) aggregation and suggests improved microvascular blood flow.
“The data from this study are consistent with observations in prior studies that MST-188 decreases blood viscosity and RBC aggregation and improves microvascular blood flow, and supportive of the potential for MST-188 to shorten the duration of sickle cell crisis,” said Martin Emanuele, PhD, of Mast Therapeutics, the company developing MST-188.
Dr Emanuele presented the study data at the recent 8th Annual Sickle Cell Disease Research & Educational Symposium.
MST-188 is a non-ionic, linear block copolymer composed of a central chain of hydrophobic polyoxypropylene and 2 flanking chains of hydrophylic polyoxyethylene. In previous studies, the agent has shown hemorheologic properties that result in improved microvascular blood flow.
For the current study, the researchers compared MST-188 to dextrans, evaluating their effects on the ESR in blood collected from SCD patients and healthy controls. Dextrans are branched polysaccharides of 10-70 kDa that have been used as antithrombotic agents and plasma expanders.
The researchers analyzed EDTA-anticoagulated whole blood collected from 8 healthy individuals and 11 SCD patients. The team treated samples with MST-188; dextran 10K, 18K , 40K, and 70K at various concentrations; or saline control.
At baseline, ESRs for SCD patients were significantly higher than for the healthy subjects. The mean ESRs were 26.4 ± 7.1 mm/hr and 14.6 ± 2.1 mm/hr, respectively.
However, adding MST-188 to the SCD patient samples decreased the mean ESR to 14.1 ± 4.6 mm/hr (Δ47%). On the other hand, comparable concentrations of dextrans showed little or no effect on the ESR in SCD samples.
The researchers said MST-188 may reduce the ESR by inhibiting acute-phase-reactant-induced RBC aggregates, and this may result from the effect of MST-188 on RBC membranes or cell-protein interactions.
Regardless of the exact mechanism, the team said lowering the ESR reflects reduced RBC aggregation and suggests improved microvascular blood flow, which indicates that MST-188 may be able to shorten the duration of vaso-occlusive crisis.
“It is widely understood that multiple biological processes contribute to vaso-occlusion and that an effective solution requires a broad, multi-modal approach rather than a single targeted therapy,” Dr Emanuele said.
“In addition to the effects on RBC aggregation, our data suggest that MST-188 addresses cell adhesion and platelet activation, reduces hemolysis, lowers blood viscosity, and limits reperfusion injury following restoration of blood flow.”
He and his colleagues at Mast Therapeutics are planning additional studies of MST-188 in SCD. The agent is currently under investigation in a phase 3 trial.
