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Therapeutic Potential of the Potassium Channel Inhibitor SHK-186 for Pediatric Lupus

Award Number: R41AI122566
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/10/2016
PERIOD OF PERFORMANCE END DATE: 12/31/2017

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Therapeutic Potential of the Potassium Channel Inhibitor SHK-186 for Pediatric Lupus - ¿ DESCRIPTION (provided by applicant): Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease with poorly understood etiology and pathogenesis and for which adequate treatment options are limited. Although dysregulated production of autoantibodies and immune complex deposition are considered hallmarks of SLE, considerable evidence supports the hypothesis that auto reactive lymphocytes are implicated in disease. SLE patients have several T cell defects including aberrant signaling, suboptimal IL-2 production, lower regulatory T cell frequencies, high CD4-/CD8- Th17 T cells, and sustained abnormally high intracellular calcium. Effector memory T cells (TEMs) decrease in circulation and increase in the kidneys and urine of lupus nephritis patients, suggesting that renal infiltration of this T ell subtype contributes to disease. Activation and inflammatory cytokine production by effector memory T cells requires expression of Kv1.3, a potassium channel needed for sustained intracellular calcium levels in effector memory T cells that have been found to be autoreactive and pathogenic in several autoimmune diseases. Here we propose to evaluate the levels of expression of Kv1.3 in SLE T cells in peripheral blood of inactive and active SLE patients compared to normal healthy controls, and test the functional effect of blocking the Kv1.3 channels in these cells with Kineta's drug candidate Kv1.3 specific peptide blocker ShK-186 (dalazatide) in terms of calcium flux and cytokine production ex vivo. In addition, we will evaluate Kv1.3 expression in kidney biopsies from patients with lupus nephritis and correlate expression to disease activity. This study will inform our hypothesis that Kv1.3 expressing T cells are pathogenic in SLE and may support considering evaluation of ShK- 186 in SLE patient populations in clinical trials.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	KINETA, INC.	219 TERRY AVE N STE 300	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	4/23/2018	NEW	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $224,977 )
2016	2016	KINETA INC	307 WESTLAKE AVENUE NORTH	SEATTLE	WA	98109	KING	USA	Allergy and Infectious Diseases Research	000	1	8/9/2016	NEW	$224,977
														Subtotal = $224,977

Grand Total All Awards = $224,977

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Therapeutic Potential of the Potassium Channel Inhibitor SHK-186 for Pediatric Lupus

Award Number: R41AI122566

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/10/2016

PERIOD OF PERFORMANCE END DATE: 12/31/2017

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