I was reviewing the VitaDOA proposals list recently and I think people might find this new research project on VitaDAO of interest. As with any targeted drug development effort there will likely be a number of compounds identified, and there may even be some compounds identified that are already available on the market. If anyone hears of any such compounds, please post details here.
Background on Hyaluronic Acid and Naked Mole Rat Longevity
From VitaDAO:
Naked mole rats (NMR) are long-lived rodents with a lifespan of up to 40 years, compared to normal rats which live about 3 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 (1). 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 (2). 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.
VDP-45 on Decentralised Tech Transfer outlined a new model of funding which, in collaboration with academic partners, conducts experiments at CRO or “fee-for-service” academic facilities. In brief, DTT allows for greater efficiency with treasury resources, speed of project initiation, and the ability to reward research collaborators for their effort.
Opportunity
Using exceptionally long-lived and cancer-resistant animals provides a strategy to identify molecular mechanisms that support longevity and healthspan, potentially uncovering novel targets and/or pathways for translation to humans. NMR, based on their size, would not be expected to live past six years, yet in some cases, live beyond 30 years. NMR also rarely get cancer, are resistant to some types of pain, and can survive up to 18 minutes without oxygen. At advanced ages, their mortality rate remains lower than any other mammal that has been documented. As such, the NMR’s biology has garnered great interest from ageing researchers.
Based on published work by the applicant, where it was found that NMR cancer resistance is conferred by abundant HMW-HA in tissue (1), the authors propose to design inhibitors against hyaluronidases, the enzymes that normally degrade HA. Furthermore, very-high-molecular-weight HA (vHMW-HA) has superior cytoprotective properties compared to the shorter HMW-HA, protecting both human and mouse cells from stress-induced cell-cycle arrest and cell death (7).
Most recently, the Gorbunova lab has found that transgenic mice that express the NMR hyaluronan synthase gene have less cancer, show improved health, and live 10% longer than mice without the transgene, supporting that higher levels of HA promote healthy living and longevity (2). While humans cannot produce vHMW-HA, it is possible to increase HMW-HA and decrease LMW-HA by inhibiting the enzyme that breaks hyaluronans down, namely hyaluronidase 2 (HYAL2). The aims of the proposed studies now intend to develop and validate HYAL2 inhibitors in order to translate these research findings into clinical applications.
Read the full Project Description Here:
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