Pharmacological inhibitors of TIA1 multimerization for prevention of neurodegeneration

This technology is a group of lead compounds that effectively prevent TIA1 multimerization and subsequent aggregation of tau protein for treatment of neurodegenerative diseases.

Unmet Need: Effective therapeutic target for stress-granules in neurodegenerative diseases

Many current treatments for tauopathies such as Alzheimer’s and ALS are cholinesterase inhibitors, which alleviate symptoms, but do not modulate the accumulation of tau protein. Recently, it has been reported that the RNA-binding protein, TIA1, mediates the accumulation of tau. As a result, TIA1 has been heavily implicated in neurodegenerative disease due to its ability to promote aggregation of disease-associated proteins. Therapeutics that disrupt TIA1 multimerization may prevent tau accumulation. To date, only signaling events upstream of TIA1 have been explored as drug targets, but these strategies are associated with significant toxicity and non-specific effects.

The Technology: Effective inhibitors of TIA1 as a potential therapy for neurodegenerative disease

This technology identifies TIA1 as a therapeutic target for treating neurodegenerative conditions, and describes lead compounds that prevent TIA1 multimerization. These compounds inhibit zinc-induced formation of stress granulates through TIA1 activity, and represent a class of compounds with mechanisms of action that may be completely distinct from those of currently available therapeutics. The compounds described in this technology potentially have less toxicity than other compounds that target neurodegeneration in the TIA1/tau/stress granule pathway. This technology has been validated with human and mouse cell lines.

Applications:

• Treatment for neurodegenerative tauopathies such as Alzheimer’s disease
• Diagnostics for tauopathies
• Treatment for stress granule-mediated disorders such as Welander distal myopathy
• Tools for preclinical models of tauopathies

Advantages:

• Identifies compounds are specific to targeting TIA1
• Prevents tau aggregation and treats tauopathy symptoms
• Minimal toxicity in animal studies
• Less toxic compared to other compounds that target neurodegeneration in the TIA1/tau/stress granule pathway

Lead Inventor:

Shi-xian Deng, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Rayman JB, Karl KA, Kandel ER. “TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2” Cell Rep. 2018 Jan; 22(1): 59–71.

Tech Ventures Reference:

• IR CU19237, CU16219, CU22124

• Licensing Contact: Jerry Kokoshka