# Targeted therapy to reverse aortic aneurysms

> **NIH NIH R01** · CLEMSON UNIVERSITY · 2024 · $634,951

## Abstract

Project Summary
Aortic aneurysms (AA) are degenerative diseases characterized by dilation caused by arterial wall
microarchitecture destruction. AAs are a life-threatening condition with the potential to lead to dissection, rupture,
and even fatality. High blood pressure, atherosclerosis, and smoking increase the risk of AA initiation and rupture.
Some inherited connective tissue disorders, such as Marfan, Loeys-Dietz, or Ehlers-Danlos syndromes, can also
increase the risk for AA. Due to procedural risks, surgical intervention is only recommended for large aneurysms
or those with a high rate of growth. However, several small aneurysms rupture while many larger ones never do.
As many as 90% of detected AAAs are small and do not meet the surgical criteria; these patients are “watchfully
waiting” without any treatment. Currently, no pharmacological approaches are available to stop AAA progression.
We have developed a novel nanoparticle (NP) delivery system conjugated with a unique elastin antibody that
targets only degraded vascular elastin, a hallmark of all aneurysms, named DESTINeD. We have discovered
elastin stabilizing and regeneration potential of polyphenol-pentagalloyl glucose (PGG) when delivered with
DESTINeD. We hypothesize that increasing the strength of the aneurysmal aorta by stabilizing residual elastin
and collagen and regenerating lost elastin will prevent the expansion and rupture of AAs.
In Specific Aim 1, we will use an abdominal aortic rupture mouse models (Angiotensin II infusion with either
intraperitoneal injection of TGF-b neutralizing antibody or adding β Aminopropionitrile, BAPN in drinking water)
to test if rupture can be prevented using DESTIENeD therapy and whether arterial homeostasis will be restored
and inflammation reduced. In Specific Aim 2, we will test the hypothesis that degraded elastin-targeting PGG-
loaded nanoparticles can prevent aneurysm rupture in a mouse model of Marfan Syndrome. Marfan syndrome
is caused by mutation of the fibrillin-1 gene that causes dysfunctional elastin deposition in connective tissues,
and many of these patients develop severe cardiovascular complications such as thoracic AAs. Fbn1R/R
homozygote mice develop ubiquitous aortic elastin fragmentation, an inflammatory-fibroproliferative response,
and inflammation-mediated elastolysis so that 99% die of aortic rupture between 2-6 months of age. Here we
will test if our nanoparticle therapy can stabilize elastin and collagen and repair ECM and prevent aneurysmal
rupture and death. As a preclinical proof for our therapy, a swine model of the abdominal AA will be used in
Specific Aim 3 to test if DESTINeD nanoparticles, with a humanized elastin antibody, would arrest growth and
reverse existing AAs. If successful, ours will be the first injectable therapy that can be translated to prevent aortic
dilation and rupture.

## Key facts

- **NIH application ID:** 10827970
- **Project number:** 5R01HL133662-06
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Naren R Vyavahare
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $634,951
- **Award type:** 5
- **Project period:** 2017-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10827970

## Citation

> US National Institutes of Health, RePORTER application 10827970, Targeted therapy to reverse aortic aneurysms (5R01HL133662-06). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10827970. Licensed CC0.

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