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

Ended Project Grant Awarded Last action

Award ID
R44NS124457
Recipient
Awarding agency
Obligated
$6,693,962

Award facts

Assistance listing
93.866 Aging Research
Completion date
Originally
Funding
  • $5,522,341.00 Federal
  • $1,171,621.00 Non-federal
Funding agency
National Institute on Aging National Institutes of Health, Department of Health and Human Services
Place of performance
Illinois, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

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, patient stratification, and the development of new diagnostic, prognostic, and therapeutic approaches.

Transactions

Action Federal Non-federal Date
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Amendment $1,003,739 $0
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Amendment $1,171,621 $0
Amendment $1,171,621 $1,171,621
Original award $1,171,621 $0
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Quick answers

Who received award R44NS124457?

R44NS124457 was awarded to Synapticure Inc. by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on February 15, 2022.

How much is award R44NS124457 worth?

$6,693,962 has been obligated on R44NS124457: $5,522,341 in federal funding and $1,171,621 in non-federal funding.

Which agency awarded R44NS124457?

National Institute of Neurological Disorders and Stroke (National Institutes of Health) awarded R44NS124457, with funding from National Institute on Aging (National Institutes of Health).

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