Human OK99 Allogeneic Stem Cell Transplantation for Patients With Severe Parkinson's Disease

This trial is a longitudinal, prospective, interventional, uncontrolled study designed to test, firstly, the safety and secondly, the potential efficacy of intraputaminal grafting of undifferentiated hfSC for the treatment of PD. Patients were monitored carefully for any adverse effects. All patients underwent baseline and 6- and 12-month post-surgery neurological, neuropsychological, MRI, and PET evaluations.

Procurement, isolation, expansion, and characterization of hfSC, as well as assessment of patients' immune response to hfSC grafting, were performed at Celavie Biosciences, LLC (Oxnard, CA USA). Patient selection, pre- and post-surgery neurological, neuropsychological, and MRI evaluations, as well as stereotactic surgery and post-surgery care, were performed at Hospital Angeles del Pedregal (Mexico City, Mexico). Synthesis of radiopharmaceuticals and PET imaging were carried out at the Radiopharmacy-Cyclotron Unit of the Faculty of Medicine, Universidad Nacional Autonoma de Mexico (Mexico City, Mexico). Eight patients with moderate to advanced PD were selected for this trial. One of the patients was lost to follow up due to reasons unrelated to this study. Subjects that completed follow up were 2 females and 5 males, with ages ranging between 43-74 years (mean age 56 years).

Procurement and expansion of hfSC

Human fetal brain tissue was procured via routine sterile manual aspiration methods with informed consent from the donor in accordance with NIH guidelines for use of fetal tissue as well as federal, and state laws. Tissue donor and hfSC recipients remained unknown to each other.

Maternal blood samples (sera) were tested for: HIV (Abbott Laboratories, Abbott Park IL, USA) hepatitis A, B and C (Abbott); HTLVI (Abbott); VDRL (Baxter Agglutination Slide Test and reflex FTA), and cytomegalovirus (Quest, Oxnard CA). Women with a history of genital herpes, cancer, asthma, lupus, rheumatoid arthritis, allergies, vasculitis of autoimmune origin, and drug abuse were excluded. Gestation was determined according to Carnegie stages. Fetal tissue was harvested at the sixth week of gestation after elective abortion. Fetal brain was dissected, minced and triturated to a single cell suspension. Cells were cultured in flasks incubated at 37°C under hypoxic conditions (5% O2 and 5% CO2) through 4 doublings. At the second doubling (D2) cell culture was tested for sterility (USP <71>) and at D4 culture was karyotyped and PCR tested for presence of adventitious agents: HTLV-1, HTLV-2, HIV-1 (A, B, D, F, H, N), hepatitis A, B and C, T. p. pallidum, CMV, HSV-1, HSV-2, HPV. Cells were then transferred to a closed bioreactor system (GE WAVE Bioreactor 2/10 System, Uppsala SWE), operating under the same physical and chemical conditions. The bioreactor was used to create the Master Cell Bank (MCB), which was harvested, tested, characterized and rate-control cryopreserved after a total of seven doublings (D7).