Association of neuraminidase regulated exocytosis with cancer metastasis (SJ-11-0012)

St. Jude Reference #SJ-11-0012

Description

Researchers have discovered a potential assay for both cancer metastasis and Alzheimer’s disease, as well as a way to use Neu1 and Neu1 activators (PPCA) to treat cancer and Alzheimer’s.

Alzheimer's disease (AD) and similar adult neurodegenerative conditions are associated with intracellular and extracellular accumulation of neurotoxic protein aggregates. Understanding how these aggregates are formed, secreted and propagated by neurons has been the subject of intensive research, but so far no preventive or curative therapy for AD is available, and clinical trials have been largely unsuccessful. Here we show that deficiency of the lysosomal sialidase NEU1 leads to the spontaneous occurrence of an AD-like amyloidogenic process in mice. This involves two consecutive events linked to NEU1 loss-of-function--accumulation and amyloidogenic processing of an oversialylated amyloid precursor protein in lysosomes, and extracellular release of Aβ peptides by excessive lysosomal exocytosis. Furthermore, cerebral injection of NEU1 in an established AD mouse model substantially reduces β-amyloid plaques. Our findings identify an additional pathway for the secretion of Aβ and define NEU1 as a potential therapeutic molecule for AD.

Keywords

Cancer metastasis, Alzheimer’s disease, neuramindase, Neu1, Neu 1 activators (PPCA)

Granted patents or published applications

Several Issued US, EU, JP, CA, AU patents; US 9,399,791; 9,840,727; 10,533,208

Related scientific references

Annunziata I, Patterson A, Helton D, Hu H, Moshiach S, Gomero E, Nixon R, d'Azzo A.; Nat Commun. 2013;4:2734. doi: 10.1038

Licensing opportunities

We are seeking partners to license this technology for the development of cancer diagnosis and treatments, as other applications (such as the neurodegenerative aspects) have been exclusively licensed. Contact: chad.riggs@stjude.org

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.