# Growth and development of Striatal-Cerebellum circuitry in subjects at risk for Huntington’s Disease

> **NIH NIH U01** · UNIVERSITY OF IOWA · 2021 · $3,901,450

## Abstract

PROJECT SUMMARY
This proposal is a competitive renewal for a unique study that measures the volume, function, and
development of striatal-cerebellar circuity in children at risk for Huntington's Disease (HD). The standard
assumption is that HD is a degenerative disease of the striatum. However, research supports supported the
notion that a crucial component of the pathoetiology of HD is abnormal brain development. The grant was
originally funded in 2009 and dubbed the Kids-HD program, designed to investigate this hypothesis by the
study of children at risk for HD (those with a parent or grandparent with HD). The at-risk participants are
genotyped and those who are gene-expanded (GE) are compared to those who are gene non-expanded
(GNE).
Gene knock-down therapy – Antisense Oligonucleotides or ASOs – are currently entering Phase III studies and
hold promise for treatment of patients in early stages of disease (by preventing further decline). If ASOs fulfill
that promise, the next step will be preventive therapy – giving the ASO early enough (potentially to children) to
prevent symptoms from occurring. The growth and development of the striatum is vital to understand as this is
the primary site of disease pathology. Yet, knocking down a gene that is vital to development of these
structures must be approached with an abundance of caution. Human brain development is prolonged, with
striatal maturational changes occurring up through 30 years of age. Therefore, discriminating ongoing
development/maturation with the degenerative phase of the disease may be key in knowing when to administer
and ASO. Our preliminary data suggest that a novel blood biomarker – Neurofilament light (NfL) rises within
roughly 20 years of onset but is normal prior to that, suggesting it is not present in development, but is seen at
the very beginning phases of degeneration.
Rationale for renewal and expansion (5 sites across the US) include: 1) increase sample size for replication of
original findings with sufficient power to detect CAG-specific effects and 2) model the entire period of brain
development (up to age 30 rather than only up to age 18); 3) evaluate the utility of a blood biomarker of neural
dysfunction, Neurofilament light (NFl) that may help delineate the earliest phases of degeneration.

## Key facts

- **NIH application ID:** 10248458
- **Project number:** 5U01NS055903-12
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** PEGGY C NOPOULOS
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,901,450
- **Award type:** 5
- **Project period:** 2009-03-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248458

## Citation

> US National Institutes of Health, RePORTER application 10248458, Growth and development of Striatal-Cerebellum circuitry in subjects at risk for Huntington’s Disease (5U01NS055903-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10248458. Licensed CC0.

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