# Measuring and Understanding Light Sensitivity in Erythropoietic Protoporphyria

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $174,960

## Abstract

PROJECT SUMMARY / ABSTRACT
Erythropoietic protoporphyria (EPP) is caused by pathogenic variants of the last enzyme of heme biosynthesis,
which produces life-long, painful cutaneous sensitivity to light. In EPP, the light-sensitive molecule
protoporphyrin IX (PPIX) accumulates in erythrocytes and secondarily in the plasma and the liver. In addition to
photosensitivity, EPP can result in anemia, gallstones, and chronic liver disease, and 2-5% patients develop
rapidly progressive cholestatic liver failure that is fatal without liver transplantation. The approval of new
therapeutics in EPP has been greatly hindered by the lack of quantitative clinical trial endpoints. While the
Food and Drug Administration recently approved one therapy that helps to prevent EPP-related
photosensitivity, no disease-modifying therapy is available for EPP. The objective of this study is to develop
methods to quantitatively measure light sensitivity in EPP and to understand the genetic basis for differences in
light sensitivity among patients. Light sensitivity will be measured by the combination of light dosimetry,
transcutaneous PPIX fluorometry, and daily text symptom surveys. The genetic basis for differences in light
sensitivity among patients will be characterized by performing whole exome sequencing and a genotyping
array in EPP patients possessing the same FECH genotype and large discordances in light sensitivity and/or
PPIX level. First, polygenic risk scores that were developed in large datasets will be applied to the genetic data
of this selected patient population. Next, disease-modifying coding variants will be identified in the exome
sequences, followed by in vitro validation. This project could lead to (1) methods to predict and prevent
photosensitivity in EPP thus improving quality of life, (2) quantitative endpoints for clinical trials facilitating the
approval of new therapies, and (3) a better understanding of the modulators of light sensitivity in EPP, which
could lead to novel therapeutics. This research will be performed by Dr. Amy Dickey, an Instructor of Medicine
at Harvard Medical School and Massachusetts General Hospital. She will receive first-rate training in statistics,
epidemiology, clinical trial design, and genetic analysis. Furthermore, she will be exceptionally mentored by Dr.
David Christiani, an expert in genetic and environmental epidemiology, and co-mentored by Dr. Mark Fleming,
an expert in heme metabolism and rare disease genetic analysis. She will perform her research in a world-
renowned academic center with all required resources available to her. Dr. Dickey's goal is to become a
physician-scientist in patient-oriented porphyria research. This K23 award will provide her with the training and
mentorship to achieve independence and apply for her first R01.

## Key facts

- **NIH application ID:** 10282590
- **Project number:** 1K23AR079586-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Amy Kathryn Yeung
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $174,960
- **Award type:** 1
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10282590

## Citation

> US National Institutes of Health, RePORTER application 10282590, Measuring and Understanding Light Sensitivity in Erythropoietic Protoporphyria (1K23AR079586-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10282590. Licensed CC0.

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