Transcriptional reprogramming platform for neuroprotection, rejuvenation, and treatment of motor neuron diseases
This technology is a gene therapy platform that selectively re-expresses the developmental transcription factors Islet1 and Lhx3 in adult motor neurons, restoring youthful resilience and protecting against neurodegeneration.
Unmet Need: Targeted, disease-modifying interventions for motor neuron degeneration
Motor neuron degeneration occurs in a range of disorders- including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), hereditary motor neuropathies, and age-associated motor decline. These conditions currently lack curative, cell-type-specific therapies. Existing treatments offer limited benefits and typically fail to modify the intrinsic vulnerability of adult motor neurons, which lose resilience with age. There is a significant need for motor-neuron-targeted therapeutic strategies that restore a youthful, protective transcriptional program and avoid off-target effects in other tissues.
The Technology: Genetic reprogramming of motor neurons to prevent motor neuron degeneration
This technology employs an adeno-associated virus (AAV)-based gene therapy method to re-express the Islet1 and Lhx3 transcription factors, thereby enhancing resilience against motor neuron degeneration. Since Islet1 and Lhx3 are normally expressed prenatally during spinal motor neuron development and are downregulated postnatally, increasing their expression in aged or vulnerable adult motor neurons can help revert these cells to a more youthful, resilient state, thereby preventing degeneration and minimizing off-target effects.
This technology has been validated in mouse models of ALS.
Applications:
- Therapeutic applications across motor neuron disorders
- Disease-modifying intervention for ALS
- Therapy for spinal muscular atrophy (SMA), hereditary motor neuropathies, and peripheral motor neuropathies
- Treatment for age-related motor neuron degeneration
- Treatment for motor neuron injury or trauma
- In vivo system to test transcription factor-based reprogramming and transcriptional rejuvenation studies * Research tool for investigating aging biology and resilience pathways in neuronal subtypes
Advantages:
- Directly targets Islet1 and Lhx3 transcription factors implicated in motor neuron development and degeneration
- Cell-type-specific targeting of motor neurons
- Proven efficacy in disease model
- Superior safety and tolerability profile
- Platform versatility across multiple diseases, delivery contexts
- Potential for integration with gene editing and precision therapeutics
- Reduces off-target side effects
- Preventive intervention
Lead Inventor:
Patent Information:
Patent Pending (WO/2024/155467)
Related Publications:
Tech Ventures Reference:
IR CU23184, CU23208
Licensing Contact: Jerry Kokoshka