# Rusalatide Acetate (TP508) Mitigation of Genotoxic Radiation Damage in Human Lens Epithelial Cells

> **NIH NIH R41** · AFFIRMED PHARMA, LLC · 2022 · $327,510

## Abstract

Cancer patients benefit from radiation therapy but can incur side effects to non-targeted tissues including
cataracts. Although not directly life threatening, cataract disease has major medical, economic, and social
impacts on individuals, families, and society as a whole. Radiation-induced lens opacification is a complex
event and has been attributed to DNA double strand breaks (DSB) in the germinative epithelium, leading to
defective differentiation of lens fiber cells and subsequent abnormal folding of lens proteins. Rusalatide
acetate (TP508) is a radio-modulating peptide that has been shown to increase survival of irradiated
animals via activation of signal transduction pathways in endothelial cells, initiating repair of DSB, increasing
NO levels and reversing of endothelial cell dysfunction. This investigation will determine if, in the absence of
endothelial cells, TP508 will have a similar effect on human lens epithelial cells (HLEC) and mitigate
radiation induced pathophysiological pathways that lead to DSB. The hypothesis is that through the direct
activation of molecular pathways in irradiated HLEC, TP508 treatment will mitigate or repair DSB. In
contrast to other investigative approaches that focus on a single downstream mechanism, this investigation
will examine molecular activity of TP508 across multiple pathophysiological pathways associated with the
health of HLEC. Study aims are to establish the molecular activity and optimum dosage thresholds, and
timing of treatments of TP508 in mitigating X-ray or proton radiation damage with single fraction exposures
of 0.5, 1.0, 2.0, or 4 Gy in HLEC (CRL-11421 [B3] and SRA01/04 lines). Aim (1) is to determine the most
optimized concentration and administration schedule for TP508 effects on radiation induced HLEC viability
using a clonogenic survival assay, MTT assay, and cell doubling time to assess the effects of various
concentrations of TP508 on the sensitivity of HLECs applied before and after irradiation. Aim (2) is to
further identify the effects of TP508 on specific HLEC molecular responses, using the most optimized
concentration and administration schedule of TP508 comparing the single fraction radiation exposures
applied with or without TP508, and analyzed with assays for apoptosis, necrosis, senescence, mitotic
catastrophe and protein expression; 53BP1 foci staining for dynamics of DSB; and western blot assays for
related signaling pathways and protein profiles including amyloid beta, an early marker of cataract
formation. Studies are expected to provide the following: (i) determine if TP508 provides a survival effect on
irradiated HLEC at different doses applied before and after radiation; (ii) identify if the molecular
mechanisms and protein profiles underlying the protective effect of TP508 in HLEC at different doses of
radiation are attributed to DSB repair; and (iii) determine the most effective dosage and timing (before or
after radiation) of TP508 application. Successfully de...

## Key facts

- **NIH application ID:** 10384634
- **Project number:** 1R41EY033583-01
- **Recipient organization:** AFFIRMED PHARMA, LLC
- **Principal Investigator:** USHA P ANDLEY
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $327,510
- **Award type:** 1
- **Project period:** 2022-02-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10384634

## Citation

> US National Institutes of Health, RePORTER application 10384634, Rusalatide Acetate (TP508) Mitigation of Genotoxic Radiation Damage in Human Lens Epithelial Cells (1R41EY033583-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10384634. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*