Wednesday, October 13, 2021 10/13/2021

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)

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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 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	Recipient Name	DUNS Number	City	State	CFDA Number	CFDA Program Title	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $134,720 )
2021	2021	UNIVERSIDAD PERUANA CAYETANO HEREDIA	934798430	LIMA		93.855	Allergy and Infectious Diseases Research	000	3	3/4/2021	NON-COMPETING CONTINUATION	$134,720


Issue Date FY: 2020 ( Subtotal = $134,720 )
2020	2020	UNIVERSIDAD PERUANA CAYETANO HEREDIA	934798430	LIMA		93.855	Allergy and Infectious Diseases Research	000	2	2/19/2020	NON-COMPETING CONTINUATION	$134,720


Issue Date FY: 2019 ( Subtotal = $134,936 )
2019	2019	UNIVERSIDAD PERUANA CAYETANO HEREDIA	934798430	LIMA		93.855	Allergy and Infectious Diseases Research	000	1	3/7/2019	NEW	$134,936


Grand Total All Awards = $404,376

Sum of Action Amount is $404,376;

Grand Total = $404,376

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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)

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