CRIB (NGF delivery) Cyto Therapeutics Inc.
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].
Cockett
M I
MI
CNS Disorders, Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA. cocketm@war.wyeth.com