Cellular Replacement by Immunoisolatory Biocapsule (
CRIB) is a technology under development by Cyto-
Therapeutics for the delivery of therapeutic substances to the central nervous system (CNS). Preclinical studies with implants are underway for the potential treatment of
Alzheimer's disease,
Huntington's chorea and other
neurodegenerative diseases [180367]. Theses implants contain cells that have been genetically engineered to secrete human
nerve growth factor. Development of the
CRIB implant is in collaboration with Genentech.
CRIB consists of product-secreting cells encapsulated in a semipermeable
polymer membrane. The device is surgically implanted into the target area of the brain, thus bypassing the blood-brain barrier, whilst isolating the foreign cells from the patient's immune system [180367].
CRIB implants secreting
nerve growth factor (
NGF) were effective in preventing
nerve degeneration in a monkey model of
Alzheimer's disease. The devices contained baby hamster kidney fibroblasts (genetically modified to secrete human
NGF) and were implanted into brain ventricles of elderly rhesus monkeys whose cholinergic neurons had been cut. The monkeys treated with non-
NGF secreting implants showed a decrease in the number of cholinergic neurons, while those treated with
NGF-secreting implants showed a smaller loss of neurons and sprouting of
cholinergic nerve fibres [200261]. CytoTherapeutics is working towards clinical trials with these implants in patients with
Alzheimer's disease [168581]. Trials of
NGF-secreting implants have also been carried out in animal models of
Huntington's disease. The company demonstrated that in rodents whose brains had been lesioned with
quinolinic acid to approximate the neuronal death which occurs in the disease,
NGF-releasing implants protected many striatal neurons that would normally have died. In addition, it was shown that behaviors normally lost as a result of striatal neuron damage could be significantly attenuated. Further investigations are scheduled for the potential use of
CRIB/
NGF technology in
Huntington's disease [180367]. The
CRIB technology was originally developed at Brown University (Rhode Island, USA) which owns several patents that cover the technology. CytoTherapeutics has entered into collaborative agreements with the university for the use of the technology [199903] as well as with NeuroSpheres, Canada, for the use of their neural stem cells [199898].