Precision modulation of synaptic chaperones for neurodegeneration treatment

This technology is a variant of the synaptic chaperon protein Hspa8, which potentiates neurotransmission to suppress spinal muscular atrophy (SMA) phenotypes in SMA model mice, with further applications in other neurogenerative diseases.

Unmet Need: Reliable, broad-spectrum disease-modifying treatments of spinal muscular atrophy (SMA) and a range of other neurodegenerative diseases

Current therapies for spinal muscular atrophy (SMA) include gene replacement and antisense oligonucleotide technologies. These techniques can improve motor function and extend patient lives, but the patient outcomes are highly variable, 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 (Hsc70), specifically the G470R missense variant, that potentiates neurotransmission through enhanced synaptic SNARE interactions. In spinal muscular atrophy (SMA) model mice, this variant suppresses SMA phenotypes and extends lifespan in SMA model mice. 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
• Potential treatment of tauopathies involving proteostasis dysfunction
• Research model for studying neurodegenerative diseases
• Platform for screening modulators that mimic or modulate Hspa8 variant effects

Advantages:

• Incorporates established gene therapy approaches
• Suppresses spinal muscular atrophy (SMA) phenotypes in SMA model mice
• Improves life expectancy in SMA mice
• Offers versatility in delivery and biochemical modulation
• Enables gene-therapy delivery formats for central nervous system and spinal cord targeting

Lead Inventor:

Umrao Monani, Ph.D.

Patent Information:

Patent Pending (US20250241968)

Related Publications:

• 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.

Tech Ventures Reference:

• IR CU23056

• Licensing Contact: Kristin Neuman