Earlier this week, JDRF announced that researchers at MIT and Boston Children’s Hospital (including notable Drs. Robert Langer and Daniel Anderson) have demonstrated that inhibition of a central component of the foreign body response selectively halts the fibrotic cascade in the presence of implanted biomaterials in rodents and non-human primates. The study, published in Nature Materials, was jointly funded by JDRF and the Helmsley Charitable Trust, and presents a novel therapeutic target for preventing immune rejection (and thereby extending wear time) of infusion sets, CGM, and cell encapsulation and transplantation devices. The authors found that colony stimulating factor-1 receptor (CSF1R) is significantly upregulated in the presence of implanted ceramic, polymer, and hydrogel. When they applied a small molecule to inhibit CSF1R function, they observed a complete loss of fibrosis. This response recapitulates that of broad immunosuppression (i.e. macrophage depletion), but it spares other critical immune functions such as wound healing, reactive oxygen species production, and phagocytosis.
Integration of a CSF1R-targeting agent into existing drug-elution systems – if it works – could represent a huge step forward in reducing the burden associated with the use of skin-penetrating medical devices. The research could also pave the way for huge progress in the beta cell encapsulation field as well – ViaCyte recently deprioritized its PEC-Encap macroencapsulation system due to variable efficacy in participants of the phase 1/2 trial, driven by the foreign body response. PEC-Encap hopes to eliminate the need for broad immunosuppressive therapies following transplantation; due to the challenges involved with the foreign body response, ViaCyte has now turned toward its less ambitious preclinical PEC-Direct project, which involves direct vascularization of the beta cells but requires chronic immunosuppressant therapy. We’re hoping that this early-stage research into CSF1R as a target to modulate the foreign body response can make macroencapsulation approaches a more viable commercial product.
In recent years, JDRF has invested heavily in a variety of devices and therapies that aim to reduce burden for people with diabetes: The organization was instrumental in bringing the automated insulin delivery field to this point (and has recently put out RFAs for reduced on-body burden/improved usability and additional input signals) and has funded multiple projects in infusion sets (including BD and Capillary/TJU) and beta cell encapsulation/transplantation (including Sernova/Defymed and ViaCyte). In addition, the new JDRF T1D Fund has recently invested in Bigfoot Biomedical, Glusense (an early-stage implantable CGM company), and (just this morning) Semma Therapeutics (Dr. Doug Melton’s company founded to commercialize his process for creating human beta cells from stem cells). This research is clearly early-stage, but signals exciting potential to improve efficacy and reduce adverse effects in a variety of areas in which the JDRF is invested.
Close Concerns Questions
Q: Are there deleterious side effects to CSF1R inhibition?
Q: Would a CSF1R inhibitor be taken systematically, or administered at the site of skin penetration? How frequently would it have to be taken/applied?
Q: How long could CGM wear feasibly be extended? Infusion set? Implantable CGM? Encapsulated islets/beta cells?
Q: How soon will we see this therapeutic tool integrated into existing devices?
-- by Brian Levine, Helen Gao, Adam Brown, and Kelly Close