Organ transplantation is an accepted therapy for various end-stage organ diseases. Systemic immunosuppression is required to prevent immunologic rejection in transplanted allografts. However, side-effects such as infections, cancers, and metabolic derangements are among the list of complications that organ transplant recipients suffer while on the necessary organ saving immunosuppressant medication. While significant advancements have been made with the design and efficacy of newer immunosuppressive medications, many carry heightened systemic risk profiles. In particular, rapamycin, has been shown to be an effective immunosuppressant, but carries an increased risk of infection, wound healing problems and metabolic side-effects.
A potential way to circumvent the systemic side-effects of rapamycin administration is to implement strategies to specifically deliver rapamycin directly to the grafted tissues. Many of the priming events that lead to the development of an alloimmune response have been shown to occur at the level of the graft. Thus, while current practice utilizes systemic immunosuppression to modulate host immunity there is a growing appreciation that immune suppression at the graft level may have more profound effects on alloimmunity whilst sparing the recipient from the complications of systemic immunosuppression.
ToleRaM Nanotech, LLC was developed to use novel graft targeting nanoparticles to attenuate both acute and chronic rejection. To facilitate graft targeting, we have conjugate these Targeted Rapamycin Micelles (TRaM) to various targeting moieties that we have extensively characterized. Ultimately, TRaM nanoparticles may be tracked, targeted to, and released at the level of a transplanted allograft as a means for drug delivery and local immunosuppression (schematic above).
Although our initial products were intially developed for transplantation, their utility is vast. The objective of our company is to utilize these nanodevices as a platform to deliver various therapeutics in a targeted fashion to specified cell types in order to alleviate a variety of disease processes. These devices are patent pending.