# Methods to Improve Clinical Trials for A-T

> **NIH FDA R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $1,600,000

## Abstract

PROJECT SUMMARY / ABSTRACT : Ataxia Telangiectasia (A-T) is a rare autosomal recessive disease
affecting ~420 individuals in the United States. It is characterized by cerebellar degeneration,
immunodeficiency, pulmonary disease and cancer susceptibility. A-T is complex and highly variable in terms of
presentation and severity, but the factors responsible for its variability are not completely understood. The
small population size, combined with wide phenotypic variability, have made clinical trials challenging. The goal
of this project is to make clinical trials for A-T as effective as possible. We will leverage the world’s largest
clinical center for A-T, 3 major university medical centers, 2 non-profits, and a parent support group to achieve
our goals. The size and diversity of the Johns Hopkins A-T patient cohort makes us well-positioned to perform
this study, which requires a highly diverse patient population. We hypothesize that it is possible to stratify
patients into severity groups that are more homogeneous than the two broad groups in use today (classic and
mild); that A-T causes upregulation of specific stress and homeostasis genes; and that an A-T specific
functional scale will capture changes in disease severity that are meaningful to patients. These hypotheses will
be tested through the following Specific Aims: 1. Prospective testing of A-T severity stratification using
genotypic, phenotypic and standard laboratory markers. There is a need to better define severity groups in A-T
beyond the current state of the art. Stratification of A-T disease severity will utilize our very large, diverse
cohort of patients with A-T and will be achieved through identification of a variety of markers that predict or
define disease severity. 2. Using RNASeq to identify systemic biomarkers that will correlate with disease
phenotypes in children and adults with A-T, to help further stratify patients into severity groups and identify
useful biomarkers for therapeutic trials. We propose that upregulation of specific stress and homeostasis
genes will be generalizable across all ages of A-T patients; that people with classic A-T will have upregulation
of specific inflammatory pathway genes compared to people with mild A-T using the classification schema in
Aim 1; and that socio-environmental exposures including neighborhood poverty and nicotine exposure will
modify gene expression differences and DNA methylation patterns in people with A-T. 3. Validating a
Functional Scale for A-T to be used as an adjunct to neurologic scoring tools in therapeutic trials. An A-T-
specific functional scale with sensitivity to capture meaningful changes in activities of daily living is essential to
clinical trials of drugs meant to slow the progression of symptoms. We will develop a quantitative model that
will provide a simple, objective way to determine disease severity in A-T, and a capture meaningful changes in
function that impact engagement and participation in activiti...

## Key facts

- **NIH application ID:** 10570376
- **Project number:** 1R01FD007605-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MAUREEN A LEFTON-GREIF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2022
- **Award amount:** $1,600,000
- **Award type:** 1
- **Project period:** 2022-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10570376

## Citation

> US National Institutes of Health, RePORTER application 10570376, Methods to Improve Clinical Trials for A-T (1R01FD007605-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10570376. Licensed CC0.

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