Development of a synthetic, cell-permeable peptide for the inhibition of CDK5-P25 hyperactivity in amyotrophic lateral sclerosis
Ended Project Grant Awarded Last action
- Award ID
- R44NS124471
- Recipient
-
Cogentis Therapeutics Inc. UEI T5K6EP6DD251
- Awarding agency
-
National Institute of Neurological Disorders and Stroke
National Institutes of Health, Department of Health and Human Services
- Obligated
- $5,483,460
Award facts
- Assistance listing
- 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
- Completion date
- Originally
- Funding
-
- $4,300,096.37 Federal
- $1,183,364.00 Non-federal
- Place of performance
- Maryland, USA
Award details come from USAspending.gov.
Description
- Abstract
- In this direct-to-phase II sbir application, cogentis therapeutics proposes to advance the development of CT526, a synthetic, cell-permeable peptide inhibitor of pathogenic CDK5-P25 as a treatment for neurodegeneration in amyotrophic lateral sclerosis (ALS). Cogentis has shown that CT526 normalizes the pathological activity of CDK5 in a mouse model of ALS while preserving essential CDK5 functionality, but additional work is needed to characterize its performance in phenotypically diverse mouse and clinically relevant human ipsc models. In addition, companion biomarkers are needed to track early responsiveness to CT526 in preclinical / clinical studies and to eventually support clinical decision-making, including drug titration. Given that the two FDA-approved drugs for ALS only provide modest benefit, further development and commercialization of CT526 and its companion biomarkers may substantially advance drug therapy for ALS, potentially providing the first treatment that slows, stops, or reverses neurodegeneration and its devastating effects on patient quality of life and survival. Aim 1. Demonstrate CT526 efficacy in a phenotypically diverse mouse model of ALS. Milestones: in the treatment group, 1) demonstrate significant delay in disease onset, prolonged lifespan, and/or improved gait and kyphosis score progression; 2) demonstrate normalization of CDK5 hyperactivity phenotype and P25 generation within 10% of the wildtype control level; 3) demonstrate reduction of p-TDP43 and NF-l in cerebrospinal fluid; and 4) demonstrate reduction of p-TDP43 and inflammatory markers in spinal cord. (p 0.65, = 20% difference between disease and control subgroups, and AUC = 80%. 4) detect = 20% reduction in CDK5 hyperactivity-related NDE biomarkers in response to CT526 treatment of mouse/ipsc models in aims 1 and 2. Impact-this project is expected to confirm CT526 efficacy in phenotypically diverse and clinically relevant models and identify an NDE-based biomarker(s) that can be used to track drug responsiveness in preclinical and clinical studies for an ALS therapeutic. In future work, cogentis will a) leverage the biomarker(s) as a tool for optimizing CT526 dosing strategies and b) conduct IND-enabling safety, efficacy, and toxicity studies of CT526.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | -$121,260 | $0 | |
| Amendment | $1,027,314 | $0 | |
| Amendment | $1,027,314 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $0 | $0 | |
| Amendment | $1,183,364 | $0 | |
| Original award | $1,183,364 | $1,183,364 |
Quick answers
Who received award R44NS124471?
R44NS124471 was awarded to Cogentis Therapeutics Inc. by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on September 22, 2021.
How much is award R44NS124471 worth?
$5,483,460 has been obligated on R44NS124471: $4,300,096 in federal funding and $1,183,364 in non-federal funding.
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