Molecular glue degraders that target APP to help prevent and treat Down syndrome-related dementia
Official title: Molecular Glue Degraders Targeting APP for Prevention and Treatment of Down Syndrome-Associated Dementia
Funded at Indiana University Indianapolis · NIH-11443073 · Data updated 2026-11-12
A new approach aims to use specialized molecules to lower APP protein and reduce brain dementia risk in people with Down syndrome.
Quick facts
| Grant type | R21 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Indiana University Indianapolis NIH-funded |
| Lab location | 1 site (Indianapolis, United States) |
| Project start | August 3, 2026 |
| Project end | July 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $435,875 |
| NIH project number | 1R21TR006460-01 |
| Project ID | NIH-11443073 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with Down syndrome who are at risk for or in the early stages of AD-like dementia may be eligible for future trials or related studies.
✕Less likely to help
Patients without Down syndrome or those not at risk for DS-related dementia are unlikely to benefit.
What this research studies
This project focuses on people with Down syndrome who are at high risk for developing Alzheimer’s-like dementia. Researchers have created molecules called molecular glues that cause APP to be degraded, which could lower harmful amyloid levels in brain cells derived from patients. The work uses stem-cell models and cellular assays to test how well these degraders reduce amyloid production and potentially slow dementia progression. If successful, the approach could lead to new treatments that specifically address the root cause linked to APP in Down syndrome.
Why it matters
Potential benefit: If the degraders work in humans, this could slow or prevent dementia in people with Down syndrome.
How similar studies have gone: Similar protein-degradation strategies have shown promise in preclinical models, but this is a novel application targeting APP in Down syndrome.
Where this research is happening
-
Indiana University Indianapolis
Indianapolis, United States Active
Researchers
- Principal investigator: Hao, Chunhai Charlie — Indiana University Indianapolis
- Study coordinator: Hao, Chunhai Charlie
Related research
Other NIH-funded projects on the same topics.
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Advance care planning for older adults with Down syndrome and early dementia
This grant tests how to prepare people with Down syndrome and their caregivers for serious illness and end-of-life care when dementia starts early.
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Understanding cognitive variability in adults with Down syndrome and its link to Alzheimer’s disease biomarkers
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Thinking variability and Alzheimer's markers in adults with Down syndrome
This project looks at whether ups-and-downs in thinking tests can signal early Alzheimer's in adults with Down syndrome.
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Understanding dementia in adults with Down syndrome
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Protein balance problems and Alzheimer's-like dementia in Down syndrome
This project asks whether disrupted protein management in the brain leads to Alzheimer's-like dementia in people with Down syndrome.
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Investigating how protein regulation affects Alzheimer's-like symptoms in Down syndrome
This study is looking at how certain proteins in the brain might be linked to Alzheimer's-like changes in people with Down syndrome, and it hopes to find ways to help keep their brains healthier.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.