Commercialization of selective DYRK1A inhibitors for down syndrome
Active Project Grant Awarded Last action
- Award ID
- R44NS129400
- Recipient
-
Iluminos Therapeutics LLC UEI QZG3UBAV73G9
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,924,902
Award facts
- Assistance listing
- 93.866 Aging Research
- Completion date 83% complete
- Originally
- Funding agency
- National Institute on Aging National Institutes of Health, Department of Health and Human Services
- Place of performance
- Oro Valley, AZ 85755, USA
Award details come from USAspending.gov.
Description
- Abstract
- Down syndrome (DS) is caused by human chromosome 21 trisomy (HSA21) and is the most common genetic form of intellectual and cognitive disability, occurring in ~1 in 700 live births. DS patients also exhibit age-related progressive cognitive decline, neurodegeneration, and the development of alzheimer's disease (ad)-like pathology by 40-50 years of age. There are currently no drugs that are approved specifically for DS to prevent cognitive decline, representing a clear and urgent unmet medical need. The progressive cognitive decline and neurodegeneration in DS is strongly linked to the overexpression of DYRK1A (dual-specificity tyrosine-(y)- phosphorylation regulated kinase 1A), which is overexpressed on HSA21 in all DS patients. Mouse models of DS that include DYRK1A overexpression exhibit profound cognitive deficits in hippocampal-dependent spatial learning and motor function associated with ad-like neuropathology. Notably, normalizing the gene dosage of DYRK1A through a genetic method in the TS65DN model of DS was sufficient to reverse several neuroanatomical ad phenotypes, and a nonselective small molecule inhibitor of DYRK1A (CX-4945) was able to reverse neurodegenerative phenotypes in DYRK1A-overexpressing mice. These data indicate that DYRK1A overexpression is a key factor in the progressive cognitive decline exhibited by DS patients and is an attractive therapeutic target. Iluminos therapeutics, LLC, (iluminos) CO-founders DR. Travis dunckley and DR. Christopher hulme have carried out a sustained medicinal chemistry effort (hulme) and validation strategy (dunckley) to develop and validate selective and efficacious DYRK1A inhibitors. Herein we propose in phase i to confirm the efficacy of our lead molecule, DYR533, in a mouse model of DS. In phase II we propose IND enabling studies to advance the commercialization efforts of this therapeutic approach. Successful completion of these phases of the proposed sttr will significantly advance the commercial prospects for iluminos' DYRK1A strategy and may ultimately lead to the availability of a much needed therapeutic option for DS patients following clinical trials in subsequent years.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $1,428,499 | |
| Original award | $1,496,403 |
Quick answers
Who received award R44NS129400?
R44NS129400 was awarded to Iluminos Therapeutics LLC by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on September 15, 2022.
How much is award R44NS129400 worth?
$2,924,902 has been obligated on R44NS129400.
Which agency awarded R44NS129400?
National Institute of Neurological Disorders and Stroke (National Institutes of Health) awarded R44NS129400, with funding from National Institute on Aging (National Institutes of Health).
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