# Novel patient-derived 3D platform for detecting TDP-43 proteinopathy and associated biomarkers for ALS/FTD

> **NIH NIH R44** · SYNAPTICURE, INC. · 2023 · $1,003,739

## Abstract

Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two of the costliest and most
devastating neurodegenerative diseases. An estimated 16,000 Americans are affected by ALS, while up to
30,000 suffer from FTD, although these are likely to be underestimates. Research in recent decades has shown
that FTD has significant clinical, pathological, and genetic overlap with ALS, and the two are now considered to
be on the same disease spectrum. Up to 50% of ALS patients experience cognitive impairment, and up to 15%
develop FTD symptoms. ALS/FTD and the morbidity and impairments they cause are accompanied by significant
medical, societal, and financial burdens. Total per patient costs are estimated at $70,000 annually for ALS
patients and $120,000 annually for FTD patients. Currently, effective diagnostics and treatments for these
diseases are lacking, and newer therapies have translated poorly to humans, despite showing great promise in
existing in vitro and animal models. A major challenge in the development and testing of new therapies is the
lack of models that accurately reflect the underlying pathophysiology. Like all neurodegenerative diseases,
animal models for ALS and FTD are hindered by the short lifespans of most animals, which may not allow for
adequate disease progression. Differences in the genomes, development, and physiology of human and animal
brains are additional complicating factors. Accurate models of these diseases are needed to advance the
development of novel biomarkers, diagnostics, and therapeutics. To address this need, SynaptiCure is
developing a novel patient-derived 3D platform for high-fidelity modeling and screening of TDP-43
proteinopathy and associated biomarkers for ALS and FTD. SynaptiCure’s innovative mAssembloids
platform will provide a new, systematic approach for creating 3D mature brain organoids that more closely reflect
disease states relevant to ALS and FTD, including matched extracellular features not seen in any other existing
models. In prior work, SynaptiCure was able to form mAssembloids from differentiated human astrocytes and
cortical-like neurons in defined numbers and ratios. mAssembloids provide a 3D environment that contains
mature astrocytes very similar to those in the healthy human brain, as well as recapitulating key features of ALS
such as aging-related disease pathology never before reported in vitro. For this Direct to Phase II project,
SynaptiCure proposes to use the mAssembloid platform to develop model systems for several different subtypes
of ALS and FTD. Specific Aims of this project are as follows: 1) Generate and validate mAssembloids for genetic
models of FTD, ALS, and FTD/ALS; 2) Generate and validate mAssembloids for C9ORF72-associated ALS/FTD;
and 3) Generate and validate mAssembloids for sporadic ALS/FTD. It is anticipated that this work will enable the
development of superior models and biomarkers that will pave the way for improvements in R&D, patien...

## Key facts

- **NIH application ID:** 10571879
- **Project number:** 5R44NS124457-02
- **Recipient organization:** SYNAPTICURE, INC.
- **Principal Investigator:** Layla Ghaffari
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,003,739
- **Award type:** 5
- **Project period:** 2022-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10571879

## Citation

> US National Institutes of Health, RePORTER application 10571879, Novel patient-derived 3D platform for detecting TDP-43 proteinopathy and associated biomarkers for ALS/FTD (5R44NS124457-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10571879. Licensed CC0.

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