Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleoside Salvage Pathway to Treat Acute Disseminated Encephalomyelitis (ADEM)

Award Number: R41AI179191
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: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2025

Group Awards By:

View Award Description

Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleoside Salvage Pathway to Treat Acute Disseminated Encephalomyelitis (ADEM) - PROJECT SUMMARY Acute disseminated encephalomyelitis (ADEM) is an acute autoimmune disease that can present with fever and ataxia as well as loss of consciousness and coma. ADEM largely affects children, is driven by T and B lymphocytes aberrantly activated against a myelin antigen, and is strongly associated with a prior infection or immunization. There is no FDA-approved therapy for the treatment of ADEM, and most cases of ADEM are treated with corticosteroids. Corticosteroids have significant side effects, including behavioral changes, hypotension, and tachycardia, and fail to address the significant morbidity and mortality associated with ADEM. Up to 50% of treated ADEM patients fail to fully recover from the disease, and ADEM has a 5 – 10% mortality rate. Our company, Trethera, has developed a small molecule drug, TRE-515, that has the potential to selectively block lymphocyte proliferation in ADEM by inhibiting deoxycytidine kinase (dCK), a key enzyme in the deoxyribonucleoside salvage pathway. Our preliminary studies show in the MOG35-55 experimental autoimmune encephalomyelitis (EAE) mouse model of ADEM that (i) immune cells activate dCK during disease, (ii) TRE-515 blocks dCK activity in immune cells, (iii) prophylactic or therapeutic TRE-515 treatments block clinical symptoms, (iv) TRE-515 treatments lead to fewer immune cell infiltrates in the central nervous system, (v) TRE-515 blocks B and T cell proliferation without affecting other immune cell types including innate immune cells or regulatory T and B cells, (vi) TRE-515 increases plasma deoxycytidine levels suggesting a potential biomarker for evaluation of drug-target engagement, (vii) TRE-515 blocks T cell proliferation in culture, and (viii) TRE-515 treatments and dCK knockout are not associated with significant toxicities. Based on these preclinical studies and due to its status as a rare disease, the FDA recently awarded TRE-515 Orphan Drug Designation (ODD) for the treatment of ADEM. This is the first and only time the FDA has awarded an ODD for the treatment of ADEM. Parallel efforts to develop TRE-515 as a cancer therapy have led to a Phase I clinical trial for solid tumors. Data from the trial show TRE-515 treatments are associated with mild side effects and show evidence of efficacy. Collectively, these data strongly suggest that TRE-515 could be an important new therapy for ADEM. In the proposed project, we will conduct critical preclinical studies to evaluate the effect of TRE-515 on immune cell development and determine whether TRE-515 can be combined with corticosteroids for the treatment of the MOG35-55 EAE ADEM mouse model. This work will be critical for moving TRE-515 into the clinic for ADEM patients and for designing clinical trials with the highest chance of success.


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 = -$4 )
2025	2024	TRETHERA CORP	13451 RAND DR	SHERMAN OAKS	CA	91423	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	8/25/2025	NON-COMPETING CONTINUATION	-$4
														Subtotal = -$4

Issue Date FY: 2024 ( Subtotal = $297,146 )
2024	2024	TRETHERA CORP	13451 RAND DR	SHERMAN OAKS	CA	91423	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	2	7/5/2024	NON-COMPETING CONTINUATION	$297,146
														Subtotal = $297,146

Issue Date FY: 2023 ( Subtotal = $304,461 )
2023	2023	TRETHERA CORP	13451 RAND DR	SHERMAN OAKS	CA	91423	LOS ANGELES	USA	Allergy and Infectious Diseases Research	000	1	7/31/2023	NEW	$304,461
														Subtotal = $304,461

Grand Total All Awards = $601,603

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleoside Salvage Pathway to Treat Acute Disseminated Encephalomyelitis (ADEM)

Award Number: R41AI179191

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: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer