This technology is a variant, mutant, or modulator of the synaptic chaperon protein Hspa8 which potentiates neurotransmission to suppress spinal muscular atrophy (SMA) phenotypes with further applications in other neurogenerative diseases including Amyotrophic Lateral Sclerosis (ALS) and tau-related dementias.
Unmet Need: Effective disease-modifying treatments of spinal muscular atrophy and other neurodegenerative diseases
Current therapies for spinal muscular atrophy (SMA) include using gene replacement and antisense oligonucleotide technologies, but there is no complete cure for SMA. These techniques can improve motor function and extend patient lives, but the patient outcomes are highly variable, can cause toxicity, and some patients miss the window of opportunity for maximum therapeutic effectiveness.
The Technology: Synaptic chaperone protein variant for treating spinal muscular atrophy and other neurodegenerative diseases
This technology is a variant of the synaptic chaperone protein Hspa8 that suppresses SMA phenotypes and extends lifetime in SMA model mice. The Hspa8 variant works by potentiating neurotransmission through interactions with synaptic SNARE complexes. The protein variant may be useful in gene therapy approaches for treating SMA as well as Amyotrophic Lateral Sclerosis (ALS) and other neurodegenerative diseases.
This technology has been validated in vivo in SMA model mice.
Applications:
- Therapy for spinal muscular atrophy (SMA) and other motor neuron diseases
- Therapy for Alzheimer’s disease and other neurodegenerative diseases
- Research model for studying neurodegenerative diseases
- Research model for studying tau-related diseases or tauopathies
- Potential combination therapy approach for current treatments for neurodegenerative diseases
- Research model for studying genetic and etiological similarities (e.g. RNA processing) between ALS and SMA
- Therapy for age-related neurological and neurodegenerative conditions
Advantages:
- Incorporates established gene therapy approaches
- Suppresses spinal muscular atrophy (SMA) phenotypes in SMA model mice
- Improves life expectancy in SMA mice
- Increases synaptic efficiency in SMA mice
- Provides platform for incorporating modulators of heat shock proteins
- Various methods of administration to the central nervous system
Lead Inventor:
Umrao Monani, Ph.D.
Patent Information:
Patent Pending (WO/2024/050560)
Related Publications:
Takeda T, Her YR, Kim JK, Jha NN, Monani UR. A variant of the Hspa8 synaptic chaperone modifies disease in a SOD1G86R mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2025 Jan;383:115024.
Fuentes-Moliz A, Kim JK, Monani U, Tabares L. “HSPA8G470R rescues neurotransmission in one-year-old control SMA mice and increases synaptic efficacy in healthy controls.” IBRO Neurosci. Rep. 2023 Oct;15(1):S309.
Kim JK, Jha NN, Awano T, Caine C, Gollapalli K, Welby E, Kim SS, Fuentes-Moliz A, Wang X, Feng Z, Sera F, Takeda T, Homma S, Ko CP, Tabares L, Ebert AD, Rich MM, Monani UR. “A spinal muscular atrophy modifier implicates the SMN protein in SNARE complex assembly at neuromuscular synapses.” Neuron. 2023 May 3;111(9):1423-1439.e4.
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