2018-028 PATHWAY-DEPENDENT INHIBITION OF PROTEOPATHIC SEED TRANSMISSION

Pathway-Dependent Inhibition Of Proteopathic Seed Transmission

 

SUMMARY

UCLA researchers in the Department of Neurology have developed a novel approach to stop the propagation of proteopathic diseases, which could be applied to wide range of neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease.

 

BACKGROUND

Proteopathy is a common feature of many neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Alzheimer’s disease market alone is expected to reach over 2.9 billion USD by 2020. Available treatments are largely ineffective, and currently there is no successful approach for modifying the disease to stop its progression. A method to neutralize the spread of proteopathy that contributes to neurodegeneration would revolutionize how we treat proteopathic neurodegenerative disorders.

 

INNOVATION

Researchers at UCLA have developed a novel approach to stop the propagation of proteopathic diseases. Recent data has shown that the proteopathy disease propagation occurs when misfolded or aggregate-prone disease-specific proteins spread to other cells. There, these proteopathic “seeds” serve as a template to cause other proteins to misfold, in a manner similar to that of prions. Researchers in the Department of Neurology at UCLA have identified a specific molecular pathway that can be inhibited to stop proteopathic seed delivery, representing a promising strategy to control progression of neurodegenerative disorders.

 

APPLICATIONS

- Alzheimer’s disease

- Parkinson’s disease

- Lewy body dementia

- Front of temporal dementia

- Amyotrophic lateral sclerosis

- Proteopathic diseases

 

ADVANTAGES

- Gives insight into proteopathic disease progression

- Applicable across multiple proteopathic diseases

- Allow discovery of new small molecule drugs for neurodegenerative disorders

 

STATE OF DEVELOPMENT

- Identified a specific molecular pathway to stop proteopathic tau seed transmission

- Identified small molecule leads that could modulate the pathway and inhibit the seed transmission

 

RELATED MATERIALS

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- Poksay, Karen S., et al. "Screening for small molecule inhibitors of statin-induced APP C-terminal toxic fragment production." Frontiers in Pharmacology 8, 46 (2017).

- Naren S., et al. “Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery” PMID 28480080 (2017)

- Heinzelman P., et al. “Nanoscale Extracellular Vesicle Analysis in Alzheimer’s Disease Diagnosis and Therapy.” Int J Alzheimer’s Disease PMID 2213078 (2016).

- Alam, MP., et al. C-O Bond formation in a Microfluidic reactor : High Yield SNAr Substitution of Heteroaryl chlorides, Tetrahedron Letters, 57, 2059-2062 (2016)

- Spilman P., et al. Netrin-1 interupts Amyloid-? amplification, increases sAPPa in vitro, and improves cognition in a mouse model of Alzheimer’s Disease. J. Alzheimer’s Dis 8, 223-242 (2016)

- Libeu CP., et al., sAPP? is a Potent Endogenous Inhibitor of BACE1, J. Alzheimer’s Dis 47, 545-555 (2015).

- Spilman, Patricia, et al. "Enhancement of sAPPa as a therapeutic strategy for Alzheimer’s and other neurodegenerative diseases." HSOA J Alzheim Neurodegener Dis 1.001 (2015).

- Theendakara, Veena, et al. "Neuroprotective Sirtuin ratio reversed by ApoE4." Proceedings of the National Academy of Sciences 110.45 (2013): 18303-18308.

Patent Information:
For More Information:
Tariq Arif
Business Development Officer
tariq.arif@tdg.ucla.edu
Inventors:
Neil Garg
Varghese John
Kanagasabai Vadivel
Barbara Jagodzinska
Tina Bilousova