Full Separator

We have shown that systemically-administered hydroxyl dendrimers target reactive microglia and macrophages and or neurons at the site of pathology, crossing the blood-brain-barrier effectively. The selecting targeting by DDC’s without a need for ligands has been validated in >50 preclinical models representing various CNS and retinal disorders, producing remarkable efficacy in AMD, diabetic retinopathy, epilepsy, depression, pain, cerebral palsy, Rett syndrome, Alzheimer’s disease, and more. The precise cell-targeting and rapid off-target clearance produces a broad therapeutic window, superior safety compared to drug, significantly improving the chances of clinical success, as shown in early Phase 1 and Phase 2 trials.

Short Separator

References.

  1. Kannan S*, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, Romero R*, Kannan RM*. Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Science Translational Medicine. 2012;4(130):130ra46. Highlighted in Nature, Science, Nature Review Drug Discovery, Chemical and Engineering News, and other media.
  2. Mishra MK, Beaty CA, Lesniak WG, Kambhampati SP, Zhang F, Wilson MA, Blue ME, Troncoso JC, Kannan S, Johnston MV, Baumgartner WA*, Kannan RM*. Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest. ACS Nano.2014;8(3):2134-2147.
  3. Zhang F, Mastorakos P, Mishra MK, Mangraviti A, Hwang L, Zhou J, Hanes J, Brem H, Olivi A, Tyler B*, Kannan RM*. Uniform brain tumor distribution and tumor associated macrophage targeting of systemically administered dendrimers. Biomaterials. 2015;52:507-16 (2015).
  4. Nance E, Zhang F, Mishra MK, Zhang Z, Kambhampati SP, Kannan RM*, Kannan S*, Nanoscale effects in dendrimer-mediated targeting of neuroinflammation. Biomaterials. 2016;101:96-107.
  5. Niño DF, Zhou Q, Yamaguchi Y, Martin LY, Wang S, Fulton WB, Jia H, Lu P, Prindle T Jr, Zhang F, Crawford J, Hou Z, Mori S, Chen LL, Guajardo A, Fatemi A, Pletnikov M, Kannan RM, Kannan S, Sodhi CP, Hackam DJ. Cognitive impairments induced by necrotizing enterocolitis can be prevented by inhibiting microglial activation in mouse brain. Science Translational Medicine. 2018;10(471), eaan0237.(Selected for Issue Cover).
  6. Kambhampati SP, Bhutto IA, Wu T, Ho K, McLeod SD, Lutty GA*, Kannan RM*, Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration, J. Controlled Release. 2021;202:335, 527-540.