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Lymphedema therapy via lymphatic targeted drug delivery

Award Number: R01HL173943
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2024
PERIOD OF PERFORMANCE END DATE: 02/28/2028

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Lymphedema therapy via lymphatic targeted drug delivery - PROJECT SUMMARY Lymphedema, which results from the failure of the lymphatic system to properly drain fluid, proteins, lipids, and immune cells from the interstitium of the skin, leads to irreversible tissue remodeling including fibrosis, swelling, and lipid accumulation. It occurs most commonly in the US as a result of cancer treatment. In breast cancer almost 1 in 3 survivors develop lymphedema and the presence has persisted in spite of reductions to the aggressiveness of cancer therapy achieved through sentinel lymph node biopsy. Being diagnosed with lymphedema remains a life sentence as there is no cure. In this project, a new therapeutic paradigm for treating lymphedema will be explored using pre-clinical models of surgically induced disease. The objective of this program is to further develop and optimize a lymphatic-targeting sustained drug delivery system for lymphedema therapy. Different types of lymphatic pump function modulators [L-type calcium channel activator and potassium channel blocker] and two classes of immunomodulators that ameliorate lymphedema- induced inflammation [inhibitors of calcineurin and transforming growth factor beta], and synergies in improving the benefits of vascularized lymph node transfer will be tested. The single vessel ligation mouse model of lymphedema will be used as, in contrast to genetic models, it is not plagued by transgene-associated immune deficiencies and closely resembles the pathophysiology of human disease. Utilizing unique dual-wavelength near infrared imaging capabilities, lymphatic function and drug biodistribution over disease progression and therapy will be tracked. This will be achieved through three specific aims: Aim 1 will focus on lymphatic delivery and effects of drugs restoring lymphatic pump function. Aim 2 will harness methods of sustained delivery into locoregional tissues as well as lymphatic delivery to lymph nodes to determine the effects of immune modulatory cargos on the immune cell populations within the draining lymph node, the resulting pathology in the lymphedematous tissue, and the consequences to lymphatic function. Aim 3 will investigate the combined delivery of lymphatic function bolstering or immune modulatory agents in a model of chronic lymphedema and synergies in combination with vascular lymph node transplant, the only existing investigational surgical intervention for lymphedema. The expected outcome of this project is a therapeutic regime for improving lymphatic function in the treatment of lymphedema, replacing watch-and-wait philosophy with low-dose (but focused) drugs that support lymphatic transport functions.


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 = $610,690 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cardiovascular Diseases Research	002	2	8/27/2025	NON-COMPETING CONTINUATION	$61,070
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cardiovascular Diseases Research	000	2	2/28/2025	NON-COMPETING CONTINUATION	$549,620
2025	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cardiovascular Diseases Research	001	1	6/3/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $610,690

Issue Date FY: 2024 ( Subtotal = $711,412 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cardiovascular Diseases Research	000	1	4/1/2024	NEW	$664,892
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cardiovascular Diseases Research	001	1	9/1/2024	SUPPLEMENT FOR EXPANSION	$46,520
														Subtotal = $711,412

Grand Total All Awards = $1,322,102

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Lymphedema therapy via lymphatic targeted drug delivery

Award Number: R01HL173943

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2024

PERIOD OF PERFORMANCE END DATE: 02/28/2028

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