MicroRNAs that target Tau protein for the diagnosis and treatment of neurodegenerative disease

This technology identifies several microRNAs specific to tangle-predominant dementia and other tauopathies that enables disease modifying therapy and improved diagnosis.

Unmet Need: Disease-modifying treatment of tangle-predominant Alzheimer’s and other tauopathies

The presence of abnormal neuronal and glial filamentous inclusions composed of the microtubule-associated protein tau defines a heterogeneous group of neurodegenerative disorders, termed tauopathies. Currently, there is no therapy that directly targets the underlying mechanisms of these diseases, including Alzheimer’s disease. Nor is there currently a way to clinically differentiate tangle-predominant dementia (TPD) from classical Alzheimer’s disease, a critical distinction for implementing amyloid beta targeted therapies. PET-based amyloid imaging may increase recognition of TPD but is cost-prohibitive. As such, there is a need for both a disease-modifying treatment as well as a bioassay that can differentiate between TPD and classical Alzheimer’s disease to enable improved diagnosis and selective treatment.

The Technology: MicroRNA signature enables identification of tangle-predominant dementia

This technology identifies a panel of microRNAs that have been shown to target and reduce the levels of Tau expression. miRNAs have recently shown great promise in treating CNS disorders and thus this technology holds great promise as a therapeutic. Additionally, using a simple bioassay, this technology enables facile clinical distinction between TPD and classical Alzheimer’s disease. As patients with TPD typically exhibit low levels of amyloid beta protein, this technology will prevent patients with TPD from being treated with general Alzheimer’s disease therapeutics that may pose an unnecessary risk. This technology also greatly improves the ability to distinguish different subtypes of dementia and may enable drug screening for therapies specific to TPD.

This technology has been validated in post-mortem Alzheimer’s patients.

Applications:

• Treatment of tauopathies including Alzheimer’s disease, tangle-predominant dementia, progressive supranuclear palsy, chronic traumatic enceohalopathy, frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTLD-tau), frontotemporal dementia, ganglioglioma, gangliocytoma, meningioangiomatosis, Pick’s disease, and corticobasal degeneration
• Identification of patients at high risk for neurodegeneration
• Targeted synthetic microRNAs for treatment of neurodegeneration
• In vitro assays or transgenic animals for drug screens that target tau expression
• Genetic markers for Alzheimer’s disease diagnosis
• Genetic markers for assessing an individual’s risk for development of age-related tauopathy

Advantages:

• Could guide development of a highly targeted TPD therapy
• Therapy may have minimal side effects, as microRNAs target specific genes for regulation
• Persistent synthetic microRNAs can be delivered to specific brain regions to avoid off-target effects in other tissues

Lead Inventor:

John F. Crary, M.D., Ph.D.

Patent Information:

Patent Status

Related Publications:

• Wang M, Roussos P, McKenzie A, Zhou X, Kajiwara Y, Brennand KJ, De Luca GC, Crary JF, Casaccia P, Buxbaum JD, Ehrlich M, Gandy S, Goate A, Katsel P, Schadt E, Haroutunian V, Zhang B. “Integrative network analysis of nineteen brain regions identifies molecular signatures and networks underlying selective regional vulnerability to Alzheimer’s disease” Genome Med. 2016 Nov 1; 8(1): 104.

• Santa-Maria I, Haggiagi A, Liu X, Wasserscheid J, Nelson PT, Dewar K, Clark LN, Crary JF. “The MAPT H1 haplotype is associated with tangle-predominant dementia” Acta Neuropathol. 2012 Nov; 124(5): 693-704.

Tech Ventures Reference:

• IR CU12162, 2957

• Licensing Contact: Ron Katz