Table 2. New therapeutic approaches under investigation or recently investigated for sickle cell disease.
| Classification and agent | Rationale/Goal | ClinicalTrials.gov registration |
|---|---|---|
| Hematopoietic stem cell
transplantation |
Replace stem cells leading to production of HbS with cells
that produce either normal or anti-sickling Hb (such as HbF) |
00408447, 01461837, 00977691,
01877837, 02065596, and 00152113 |
| Gene transfer or correction | Replace or correct the HbS gene with a gene encoding either
normal or anti-sickling Hb (such as HbF) |
02186418, 02140554, and 02151526 |
| Nutritional supplements | ||
| • L-glutamine | Lower energy requirements to improve growth and strength | 01179217, 00131508, 00586209,
and 00125788 |
| • Niacin | Improve blood flow | 00508989 |
| • Vitamin D | Correct chronic vitamin D deficiency common in children with
SCD |
01276587 |
| • Alpha-lipoic acid and
acetyl-L-carnitine |
Anti-oxidant | 01054768 |
| • Arginine | Improve availability of NO | 00513617 |
| Anti-inflammatory | ||
| • Regadenoson | Downregulate the activity of iNKT cells | 01566890 and 01085201 |
| • NKTT120 | Deplete iNKT cells | 01783691 |
| • Zileuton | Reduce inflammation | 01136941 |
| • Montelukast | Reduce soluble vascular cell adhesion molecule-1 (sVCAM-1) | 01960413 |
| • IVIg | Shorten VOC | 01757418 |
| Anti-adhesive | ||
| • Propranolol | Reduce activation of red cell adhesion receptors activated via
beta adrenergic receptor signaling pathways |
01077921 and 02012777 |
| • SelG1 | Block adhesion via P-selectin to prevent VOC episodes | 01895361 |
| • PF-04447943 | Phosphodiesterase-9 inhibitor | 02114203 |
| • Rivipansel | Reduce adhesion and inflammation dependence on E-selectin | 01119833 and 02187003 |
| Anti-sickling | ||
| • MP4CO | Reduce sickling by delivering CO | 01356485 |
| • SCD-101 | Reduce sickling | 02380079 |
| • Sanguinate (PEG-bHb-CO) | Reduce sickling by delivering CO | 01848925 |
| • AES-103 | Reduce sickling | 01987908 |
| Alter hemoglobin expression | ||
| • Vorinostat | Increase HbF | 01000155 |
| • HU with Mg Pidolate | Increase both HbF and cell hydration | 00143572 |
| • HQK-1001 | Increase HbF | 01601340 |
| • Panibostat | Increase HbF | 01245179 |
| • Decitabine | Increase HbF | 01375608 and 01685515 |
| • Pomalidomide | Increase HbF | 0522547 |
| Anti-coagulant and anti-platelet | ||
| • Ticagrelor | Decrease vaso-occlusive episodes and pain | 02214121 |
| • Prasugrel | Decrease vaso-occlusive episodes and pain | 01167023, 01794000, and 01476696 |
| • N-acetyl cysteine | Decrease VWF levels, VWF total activity, ULVWF multimers,
and VWF functions |
01800526 |
| • Aspirin | Diminish the incidence and progression of cognitive deficits
as well as occurrence of overt and silent stroke |
00178464 |
| • Eptifibatide | Reduce platelet activation and release of pro-inflammatory
cytokines |
00834899 |
| Other | ||
| • Inhaled NO | Improve pulmonary hypertension | 00023296 |
| • ICA-17043 | Reduce hemolysis and VOC by increased cell hydration | 00040677 |
| • Intravenous NO | Vaso-dilation | 00095472 |
| • Losartan | Improve SCD nephropathy | 02373241 |
| • 6R-BH4 (sapropterin
dihydrochloride) |
Improve endothelial dysfunction | 00445978, 00403494, and 00532844 |
| • Magnesium sulfate | Reduce length of stay and pain in children with acute VOC | 00313963 |
| • Varespladib (A-001) | Decrease acute chest syndrome | 01522196 and 00434473 |
| • Atorvastatin | Improve endothelial dysfunction | 00072826 |
| • Simvastatin | Improve endothelial dysfunction | 00508027 |
| • Bosentan | Improve pulmonary hypertension | 00313196, 00360087, and 00310830 |
| • Clotrimazole | Reduce hemolysis and anemia by blocking Gardos channel | 00004404 and 00004492 |
CO, carbon monoxide; Hb, hemoglobin; HbF, hemoglobin F; HbS, hemoglobin S; HU, hydroxyurea; iNKT, invariant natural killer T; NO, nitric oxide; SCD, sickle cell disease; ULVWF, ultra-large von Willebrand factor; VOC, vaso-occlusive crisis; VWF, von Willebrand factor.