Therapy for Vaso-Occlusive Crisis in Sickle Cell Disease

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Sickle cell disease (SCD) is a chronic disease as patients suffer from recurring episodes of sickle cell crisis, extreme pain associated with the obstruction of one or more blood vessels and resultant inflammatory events. A clustering of sickle cells, possibly due to microparticle release during oxidative stress, has been associated with the onset of vascular obstruction. Severe pain results when blood vessels are blocked; this vaso-occlusive crisis (VOC) has been described as severe and life-limiting. Currently, the management of VOC requires hospitalization, which usually begins in the emergency room, chronic administration of the drug hydroxyurea, and episodic administration of opioid analgesics such as morphine. Frequent opioid use induces drug tolerance, increased dosing, and problems with dependence, which further increases the burden on patients.

The root of the problem in SCD arises from issues in band 3, a red blood cell membrane protein, which is hyperphosphorylated. However, the most influence on band 3 comes from spleen tyrosine kinase (SYK), which seems to phosphorylate tyrosine 8 and 21 on band 3. The use of SYK inhibitors in these cases will significantly decrease both band 3 phosphorylation, decrease the number of microparticles in circulation, and prevent the initiation of thrombosis and VOC. By using this concept to find a therapeutic replacement, researchers at Purdue University have proposed the use of a prophylactic treatment with a SYK inhibitor, which could reduce or eliminate the recurrence of sickle cell crisis in both adults and children suffering from SCD. Patients can be administered an inhibitor, such as GleevecĀ® (imatinib mesylate), an orally-dosed, antineoplastic drug for the treatment of cancers, such as metastatic malignant gastrointestinal stromal tumors, chronic myeloid leukemia, relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia, and chronic eosinophilic leukemia. This would be a new, off-label indication of this medication, but the dosage used would still fall within guidelines previously established in the original, approved indication, thus making this safe.

-Efficient inhibition of band 3 phosphorylation
-Prevention and/or reduction of vaso-occlusive events
-Less complicated therapy and management

Potential Applications:
-Pharmaceutical Industry
-Sickle cell disease treatment
Oct 13, 2017
United States

Apr 14, 2016

Apr 14, 2015
United States

United States
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