# Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions

> **NIH NIH K23** · JOHNS HOPKINS UNIVERSITY · 2024 · $195,587

## Abstract

PROJECT SUMMARY/ABSTRACT
 This proposal describes a 5-year training award to develop the academic career of the principal
investigator, Melanie C. Dispenza, MD, PhD, a board-certified allergist-immunologist at the Northwestern
University Feinberg School of Medicine. Her qualifications and background, combined with her current research
in preventing IgE-mediated activation of mast cells and basophils, make her uniquely qualified to study novel
therapies to prevent anaphylaxis. During the period of this proposal, Dr. Dispenza will continue to devote at least
75% effort towards patient-oriented translational research.
 Anaphylaxis is a potentially life-threatening IgE-mediated systemic allergic reaction with no known
preventative therapies. There is a huge unmet need for therapies that can reduce the frequency and/or severity
of anaphylactic reactions from both accidental and intentional exposures, the latter including desensitizations
and immunotherapy. Bruton’s tyrosine kinase (BTK) is a key component of FcεRI signaling in human mast cells
and basophils. Pharmacologic inhibitors of BTK are generally well tolerated, and preliminary data show that BTK
inhibitors effectively block IgE-mediated human mast cell and basophil activation in vitro and in mouse models
of anaphylaxis in vivo. Thus, it may be possible to utilize BTK inhibitors to proactively prevent allergic reactions
including anaphylaxis. The overarching hypothesis of this proposal is that short-term use of FDA-approved BTK
inhibitors such as ibrutinib will prevent medication-induced anaphylaxis in both mouse models of anaphylaxis
and in humans. If successful, BTK inhibitors could potentially be used to make drug desensitization safer and
more cost effective, thus improving patient care and outcomes.
 Through this proposed research, Dr. Dispenza will work towards her long-term goal of becoming an
independent translational physician-scientist. Short-term goals include (1) expanding research skills in mast cell
biology, (2) learning to implement novel humanized mouse models of anaphylaxis, and (3) acquiring biostatistical
and clinical trial skills for study design and implementation. After completion of this award, Dr. Dispenza will
have had the needed training to design and implement further studies on the development of novel strategies to
prevent anaphylaxis. To achieve these goals, an excellent mentoring team has been assembled. The primary
mentor, Bruce Bochner, MD (Professor, Division of Allergy-Immunology, Department of Medicine), has a strong
track record of translational research in allergy including mast cell biology and has successfully trained many
academicians. Donald MacGlashan, Jr, MD, PhD (Director, Division of Allergy and Clinical Immunology, Johns
Hopkins University), will serve as co-mentor, with additional expertise in mast cell and basophil activation and
signaling. The mentoring team will oversee Dr. Dispenza’s progress in developing the necessary skills in order
to supp...

## Key facts

- **NIH application ID:** 10763003
- **Project number:** 5K23AI143965-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Melanie C. Dispenza
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,587
- **Award type:** 5
- **Project period:** 2020-02-22 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763003

## Citation

> US National Institutes of Health, RePORTER application 10763003, Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions (5K23AI143965-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10763003. Licensed CC0.

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