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Alternative therapeutic approaches for the control of brain inflammation secondary to antihelminthic therapy in neurocysticercosis using a novel experimental pig model

Award Number: R01AI143553
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: 03/08/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Alternative therapeutic approaches for the control of brain inflammation secondary to antihelminthic therapy in neurocysticercosis using a novel experimental pig model - Alternative therapeutic approaches for the control of brain inflammation secondary to antihelminthic therapy in neurocysticercosis using a novel experimental pig model PROJECT SUMMARY Neurocysticercosis (NCC) is the infection of the human brain by the larvae of the pork tapeworm Taenia solium and is a major cause of seizures in most of the world. Antihelminthic therapy induces cyst damage and activates the host immune response, which results in brain inflammation and edema. Corticosteroids are commonly administered concomitant with antihelminthic drugs to control the early treatment-induced inflammatory response. However, an ideal therapeutic scheme using corticosteroids has not been established, corticosteroid therapy is suboptimal in some forms of NCC, and its use may also lead to undesirable side- effects. A better understanding of the immunopathological processes associated with CNS cyst infection and in response to antihelminthic therapy is essential to improve the control of the treatment-induced brain inflammation and to evaluate potential corticosteroid-sparing/replacing agents. The lack of an appropriate animal model for NCC has however, limited our ability to achieve these goals. We recently demonstrated that intra-carotid injection of T. solium activated oncospheres in pigs reproduces CNS cyst infection efficiently, thus providing a suitable animal model for the study of NCC. In this proposal, we will optimize the intra-carotid injection model by determining the number of activated oncospheres required to consistently reproduce NCC in pigs, as well as to characterize the immunopathological processes associated with CNS cyst infection and in response to antihelminthic therapy with albendazole plus praziquantel. Subsequently, we will conduct two trials in pigs with experimental NCC: In the first trial, we will determine the optimal dose of two alternative anti-inflammatory drugs: etanercept (ETN) or methotrexate (MTX) in the control of the brain inflammatory response that results from antihelminthic therapy; the second trial will compare the optimal dose of ETN and MTX versus the wide-spectrum, corticosteroid dexamethasone (DEX) in the control of pericystic brain inflammation after antihelminthic therapy. We expect that our findings will provide the base evidence for translational studies testing ETN or MTX in controlled studies in NCC patients.


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: 2025 ( Subtotal = -$146 )
2025	2023	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AVENIDA HONORIO DELGADO 430 URB URB INGENIERIA	LIMA				PER	Allergy and Infectious Diseases Research	000	5	8/7/2025	NON-COMPETING CONTINUATION	-$146
														Subtotal = -$146

Issue Date FY: 2023 ( Subtotal = $134,720 )
2023	2023	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AVENIDA HONORIO DELGADO 430 URB URB INGENIERIA	LIMA				PER	Allergy and Infectious Diseases Research	000	5	3/1/2023	NON-COMPETING CONTINUATION	$134,720
														Subtotal = $134,720

Issue Date FY: 2022 ( Subtotal = $134,720 )
2022	2022	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AV. HONORIO DELGADO 430	LIMA	LIMA			PER	Allergy and Infectious Diseases Research	000	4	3/1/2022	NON-COMPETING CONTINUATION	$134,720
														Subtotal = $134,720

Issue Date FY: 2021 ( Subtotal = $134,720 )
2021	2021	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AV. HONORIO DELGADO 430	LIMA	LIMA			PER	Allergy and Infectious Diseases Research	000	3	3/4/2021	NON-COMPETING CONTINUATION	$134,720
														Subtotal = $134,720

Issue Date FY: 2020 ( Subtotal = $134,720 )
2020	2020	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AV. HONORIO DELGADO 430	LIMA	LIMA	15102		PER	Allergy and Infectious Diseases Research	000	2	2/19/2020	NON-COMPETING CONTINUATION	$134,720
														Subtotal = $134,720

Issue Date FY: 2019 ( Subtotal = $134,936 )
2019	2019	UNIVERSIDAD PERUANA CAYETANO HEREDIA	AV. HONORIO DELGADO 430 URB. INGENIERIA	LIMA		31		PER	Allergy and Infectious Diseases Research	000	1	3/7/2019	NEW	$134,936
														Subtotal = $134,936

Grand Total All Awards = $673,671

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Alternative therapeutic approaches for the control of brain inflammation secondary to antihelminthic therapy in neurocysticercosis using a novel experimental pig model

Award Number: R01AI143553

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: 03/08/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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