Matrix Bio

Background

Naked mole rats (NMR) are long-lived rodents with a lifespan of up to 40 years, compared to normal rats which live about three years. Unlike other rodents, NMR are found to be cancer resistant. Previous research by the Gorbunova lab has demonstrated cancer resistance in NMR is modulated by the abundance of high molecular weight hyaluronic acid (HMW-HA) in tissues. Additional research has demonstrated that transgenic mice expressing naked mole rat hyaluronan synthase gene (NHAS2) have less tumours, improved health, and live 10% longer than mice without the transgene. 

Aims, Hypothesis & Results

To increase HA in human patients and translate these findings into the clinic, this project will screen and develop small molecule inhibitors of hyaluronidases, the enzymes that break down hyaluronic acid. These compounds can be used for cancer treatment and are expected to increase human healthspan and lifespan.

Timeline

Program 1: HTS and med chem for new inhibitors

Phase 1: High Throughput Screening (HTS) – up to $100k

Phase 2: Medicinal Chemistry on hits – up $100k

Program 2: Validation of existing in vivo active inhibitor (EC50 ~ 20 µM)

Administration of hit compound to mouse models of cancer to test for curative and preventative effects - up to $100k
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VitaDAO Board Evaluation Writeup

Vera Gorbunova is a world leader in the field of comparative biology with a focus on longevity and healthspan mechanisms. She proposes a unique approach with relatively little competition on the MoA and a straightforward road to NCE IP. There is strong published and supporting evidence for the target in mice. The mechanism for cancer prevention seems to be well established via CD44. There is already a screen hit with a potential asset in hand. This could be a first DeSci project, where the DAO is spinning out the company and that is a step forward for the community.

However, the hyaluronan role in cancer is somewhat controversial: on one hand, HMW-HA production is linked to cancer resistance, on the other hand, HMW-HA is involved in driving and maintaining malignant progression. The underlying hypothesis needs more PoC data to be further substantiated. It is unclear if the proposed intervention would work systemically to increase life/health span and reduce cancer in humans. The project is early and very high risk, but no insurmountable weaknesses.

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