GENE-THERAPY FOR AMYOTROPHIC-LATERAL-SCLEROSIS (ALS) USING A POLYMER ENCAPSULATED XENOGENIC CELL-LINE ENGINEERED TO SECRETE HCNTF

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human cilia ry neurotrophic factor (hCNTF) for the treatment of Amyotrophic Latera l Sclerosis (ALS). A tethered device, containing around 10(6) genetica lly modified cells surrounded by a semipermeable membrane, is implante d intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 mu g/24 hours. The semipermeable membrane prevent s immunologic rejection of the cells and interposes a physical, virall y impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydr ofolate reductase-based selection vector with a SV40 promoter and cont aining a HSV-tk killer gene. hCNTF is a potent neurotrophic factor whi ch may have utility for the treatment of ALS. Systemic delivery of hCN TF in humans has been frustrated by peripheral side effects, the molec ule's short half life, and its inability to cross the blood-brain barr ier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant .