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1045 Successful Treatment of Thrombocytopenia with Staphylococcal Protein A (PRTX-100) in a Murine Model of Immune Thrombocytopenia (ITP)

Disorders of Platelet Number or Function
Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

John W. Semple, PhD1, Edwin R. Speck, BRT1*, Rukhsana Aslam, PhD1*, Michael Kim, BSc1*, Anne Zufferey, PhD1*, Heyu Ni, MD, PhD2, Michelle Catalina, PhD3* and Richard Francovitch, PhD3*

1St. Michael's Hospital, Toronto, ON, Canada
2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
3Protalex Inc., Florham Park, NJ

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and autoreactive T cells target the destruction of platelets and megakaryocytes in the spleen and bone marrow.  Several therapeutic options e.g. steroids, IVIg, Rituximab and thrombopoietin mimetics, are available for patients but inadequate efficacy, side effects and/or expense can make them undesirable.  PRTX-100 is a highly purified formulation of Staphylococcal Protein A that has been evaluated in clinical trials with rheumatoid arthritis patients.  Here, we analyzed the efficacy of PRTX-100 in raising platelet counts in a well-established murine model of ITP that demonstrates both antibody- and T cell-mediated thrombocytopenia. Platelet glycoprotein (GP) IIIa (CD61) knockout (KO) mice were immunized with CD61+ platelets and ITP was initiated by transfer of their splenocytes into severe combined immunodeficient (SCID) mice. On day 10, post transfer, the SCID mice were treated with either placebo, 1g/kg IVIg (ip, biweekly) or doses of PRTX-100 (iv, biweekly, 2.5-250 ug/kg) and platelet counts were measured weekly.  Results show that control SCID mice transferred with 1x104 splenocytes from immune CD61 KO mice became thrombocytopenic at day 7 post-transfer and remained extremely thrombocytopenic throughout the 28 day protocol (3 mice died from bleeding diatheses).  Similar observations were found with SCID mice given placebo.  In contrast, however, transferred SCID mice treated with either IVIg or the PRTX-100 doses had platelet counts that increased to within normal levels within 1-2 weeks after treatment and none of the mice died (Table 1).

Table 1.  Platelet counts (mean+SD) in SCID ITP mice (N=3-8/group) treated with the indicated compounds.

Treatment

Pre-bleed

Day 14

Day 21

Day 28

No treatment

848+202

89+46

51+42

78+51

Placebo (250 ug/kg)

848+202

113+59

46+20

63+40

IVIg (1 g/kg)

848+202

290+211

490+289

698+350

PRTX-100 (250 ug.kg)

848+202

101+37

303+112

505+226

PRTX-100 (25 ug.kg)

848+202

203+88

290+67

254+70

PRTX-100 (2.5 ug.kg)

848+202

275+202

405+289

631+401

These results demonstrate that PRTX-100 was effective in elevating platelet counts in a murine model of human ITP and support the proof of principle that PRTX-100 may be beneficial in patients with ITP.

Disclosures: No relevant conflicts of interest to declare.

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