# Targeting Complement 5a-Mediated Immunoregulation for Neurofibroma Therapy

> **NIH NIH R33** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $397,451

## Abstract

Principal Investigator/Program Director (Last, first, middle): Wu, Jianqiang/Ratner, Nancy
Abstract
Neurofibromatosis type 1 (NF1) is a common inherited human disorder affecting about 1:2500
individuals worldwide. About half of NF1 patients develop plexiform neurofibromas, benign but
devastating peripheral nerve tumors; surgical removal is often impossible due to the integration of
tumor in critical peripheral nerves. We found that MEK inhibition shrinks 70% of tumors in
DhhCre;Nf1fl/fl neurofibroma-bearing mice. This result in a mouse model predicted success of a
phase I/II clinical trial for children with NF1 and large inoperable plexiform neurofibroma, in which
MEK inhibition using Selumetinib in showed unprecedented activity, with 70% of patients
experiencing sustained partial responses. However, the maximal tumor volume decrease was 50%,
and continued MEK inhibition was required for sustained response. Therefore, we searched for
genes, proteins, and pathways that are not normalized by MEK inhibition. Based on our promising
preliminary data, we will test the therapeutic effects of targeting the one of these, the C5a/C5aR
pathway in plexiform neurofibroma. The work proposed in this application will test if C5a is a
therapeutic target for plexiform neurofibromas, alone or in combination with MEK inhibition. We will
measure PK and PD, and efficacy. Our multidisciplinary team includes world leaders in neurofibroma
preclinical testing, an expert in volumetric measurement for neurofibroma, a biostatistician, and
experts in the biology of the complement system who developed unique antagonists of C5aR, and
NF1 clinicians.

## Key facts

- **NIH application ID:** 10320559
- **Project number:** 4R33NS112407-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** NANCY RATNER
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,451
- **Award type:** 4N
- **Project period:** 2019-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320559

## Citation

> US National Institutes of Health, RePORTER application 10320559, Targeting Complement 5a-Mediated Immunoregulation for Neurofibroma Therapy (4R33NS112407-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10320559. Licensed CC0.

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