Mesentech’s Bone Targeting Technology can accurately target and deliver small molecule compounds and proteins directly to bone.

The Mesentech bone targeting technology uses as its targeting mechanism, a bisphosphonate drug (such as alendronate) that seeks out and binds tightly to bone. To this is attached a proprietary linker, which itself is attached to the required therapeutic drug (or therapeutic protein of interest). Together these form a conjugate of targeting drug linked to an active therapeutic drug. The linker is attached to and blocks that part of the bisphosphonate molecule that would, if used alone, have a pharmacological effect on bone resorption. Thus the bisphosphonate retains its bone targeting function, but remains inactive. The required therapeutic drug has now been delivered to the bone, where, through local action of enzymes or other factors, it becomes released from the conjugate and is then active at the required site.

The technology can be “dialed-in” to change the characteristics of active drug release, such as site specific and/or time specific release, as required. The linker technology that attaches the active compound to the inactive carrier targeting compound can be adapted to release the active compound on either the surface of the bone or the inside of the bone, as required, using various naturally occurring substances, such as site specific enzymes or even pH. By controlling the rate of release the technology can provide therapies that require infrequent dosing (once a week or longer). This technology thus opens up the door to a significantly improved means of site-directed clinical treatment, getting drug to and released exactly where it is required. This therefore can significantly improve efficacy whilst potentially reducing timelines for treatment and reducing side-effects.

Gene Directed Therapy

Many genes are known to be active in the formation, healthy functioning and breakdown of bone. Mesentech is developing new technological approaches that will allow for the required “knock-down” or “knock-up” of specific bone related genes to induce bone growth or regeneration.

An example of a gene, the knock-down of which would result in stimulation of bone growth is SOST, which encodes for the signaling protein known as sclerostin. Sclerostin modulates activity of the WNT pathway andinhibits bone formation, thus blocking the production of this protein, by inhibiting the gene which encodes for it, should have a beneficial effect on enabling increased bone formation to occur. This could prove to be very beneficial in treating diseases such as osteoporosis, where bone density is lost and bones become fragile and may fracture easily.

Mesentech is working on a nano-particle technology that can deliver siRNA for SOST to bones resulting in a knock-down of the gene. This technology could have a wider application across many other disease related genes.