# Clinical Research in ALS & Related Disorders for Therapeutic Development (CReATe) - Project Core #2

> **NIH NIH U54** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2021 · $412,831

## Abstract

Project Summary / Abstract
There is marked phenotypic variability among patients with amyotrophic lateral sclerosis (ALS) and related
disorders, such as frontotemporal dementia (FTD), primary lateral sclerosis (PLS), progressive muscular
atrophy (PMA), and hereditary spastic paraplegia (HSP), with respect to age and site of disease onset, upper
versus lower motor neuron pathology, presence and degree of cognitive dysfunction, rate of disease
progression and survival from disease onset. To explore this heterogeneity, we will examine a well-
characterized cohort of patients enrolled in the CReATe Consortium’s Phenotype-Genotype-Biomarker (PGB)
Protocol, for whom we have collected a wealth of clinical and genomic data. We aim to identify genetic variants
that modify underlying phenotypic characteristics of ALS and related diseases (age at onset, rapid versus slow
disease progression, cognitive impairment, survival from onset). Our strategy will include innovative
approaches (e.g., detection of retroelement insertion and viral integration) and cutting-edge technology (long-
read single-molecule real-time [SMRT] sequencing) to uncover variation that has been missed thus far.
Additionally, we will explore gene-environment interactions in a targeted manner by focusing on variants in
protein folding and DNA repair pathways and environmental risk factors (e.g., cigarette smoking). Replication will
be conducted in studies through our large collaborative network. The factors we identify through our studies will
enhance our ability to decipher the basis for the phenotypic heterogeneity of this group of diseases and will be critical
to the success of future clinical trials.

## Key facts

- **NIH application ID:** 10242883
- **Project number:** 5U54NS092091-08
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Joseph Paul Taylor
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,831
- **Award type:** 5
- **Project period:** 2014-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242883

## Citation

> US National Institutes of Health, RePORTER application 10242883, Clinical Research in ALS & Related Disorders for Therapeutic Development (CReATe) - Project Core #2 (5U54NS092091-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242883. Licensed CC0.

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