Safety Study of Human Neural Stem Cells Injections for Secondary Progressive Multiple Sclerosis Patients
A Phase I Multicenter Study of Allogenic, Intracerebroventricular Human Neural Stem Cells Transplantation for the Experimental Treatment of Secondary Progressive Multiple Sclerosis Patients
This will be a phase I, open, multicenter, international study performed by 3 participating centres across two countries (Italy and Switzerland). Fifteen to 24 patients affected by SPMS will be enrolled, according to a "standard" phase I design over 18 months. All patients will enter a 3 months run in phase. Thereafter they will receive one of four different doses of allogenic hNSCs (dose A=5 millions hNSCs; dose B=10 millions hNSCs; dose C=16 millions hNSCs; dose D=24 millions hNSCs). Following hNSCs injection, all SPMS patients will receive immunosuppression with tacrolimus for 6 months. Patients will be clinically followed monthly for 1 year and then every 6 months for the 5 years following the study completion (possibly all life long).
MRI assessments will be performed monthly for the first 6 months and then every 3 months for 5 years following the study completion.
Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10, 16 or 24 millions). hNSCs are produced by the Laboratorio Cellule Staminali of Terni according to GMP guidelines and are obtained from brain specimens of several fetal human donors from spontaneous miscarriages occurred after the 8th week after conception.
Intraventricular injections of Allogenic human Neural Stem Cells (hNSCs) in four different dosages (5, 10,16 or 24 millions)
Inclusion Criteria: SPMS with progressive accumulation of disability after initial relapsing course, with or without disease activity (Lublin et al. 2014). EDSS ≥ 6.5 and ≤ 8 EDSS progression over the 2 years prior to study start of ≥ 1.0 point for patients with EDSS =6.5 at the time of inclusion , and of ≥ 0.5 points for patients with EDSS > 6.5 at the time of inclusion Age ≥ 18 and ≤ 60 years Failure of best medical treatment as judged by the treating neurologist and declared absence of therapeutic alternatives Exclusion Criteria: Neurological conditions other than MS. Psychiatric disorders, severe cognitive decline and personality and relational disorders. History or known presence of significant systemic, infectious, oncologic or metabolic disorders. Presence of any other autoimmune disease. Chronic infections (HBV, HCV, HIV, tuberculosis). Inability to perform MRI scans. Immunomodulant/immunosuppressive treatments in the last 6 months before inclusion. Current participation to other experimental studies. Inability to provide informed consent. Any contra-indication to lumbar puncture and the surgical procedure (e.g. use of anticoagulants) Pregnancy and breast feeding.