Artikel
Safety and toxicity of fetal whole ganglionic eminence progenitor cell transplantation in Huntington's Disease patients
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Autoren
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Tobias Piroth
- Neurological Clinic, University Hospital of Freiburg, Germany; Department Stereotactical Neurosurgery, University Hospital of Freiburg, Germany
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Elisabeth Schültke
- Department Stereotactical Neurosurgery, University Hospital of Freiburg, Germany
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Michael Trippel
- Department Stereotactical Neurosurgery, University Hospital of Freiburg, Germany
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Jaroslaw Maciaczyk
- Department of general Neurosurgery, University Hospital of Freiburg, Germany
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Guido Nikkhah
- Neurological Clinic, University Hospital of Freiburg, Germany
| Veröffentlicht: | 16. September 2010 |
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Gliederung
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Objective: The European multicentre trial MIG-HD aims on the replacement of lost striatal projection neurons using fetal progenitor cells. Available data from the German branch of the trial provides information on side effects and benefits. Risk assessment is based on pharmacological safety, involving immune rejection, tumour formation, disease transmission and side effects of immune suppression.
Methods: Patients enrolled in the trial received fetal ganglionic eminence derived grafts stereotactically implanted into up to six trajectories of the striatum bilaterally. Fetal tissue was obtained from elective abortions. Blood samples from women undergoing abortions were analyzed for HIV, HBV, HCV and HTLV. Testing for bacterial contamination was performed after implantation.
Results: 15 patients were transplanted bilaterally and 2 unilaterally, receiving tissue from 1–2 donors/side. Age at enrolment ranged from 31 to 53 years. Prior to transplantation, in 50% of patients, antibodies raised against EBV and in 100% of patients, antibodies against CBV could be detected. There was no transmission for HIV, HBV, HCV or HTLV.
Beside one bacterial infection (Staphylococcus spc.), there was no side effect directly associated with the surgery. One patient suffered from a subdural haemorrhage after head injury. Another patient with the diagnosis of a chronic depression committed suicide. The most common side effects were associated with immune suppression. There was no case of graft overgrowth. We did not register secondary tumour formation and no symptomatic CMV reactivation. Development of HLA conversion was noted in two cases, requiring prolonged immune suppression. One patient detoriated closely after withdrawal of immune suppression and improved after administration of high-dosed steroids.
Conclusions: Clinical progenitor cell transplantation was not associated with increased risk for viral transmission and tumour formation. The most serious side effect was impairment of kidney function. Induction of HLA antibodies and clinical signs of graft rejection suggest immunogenity of grafts and might be responsible for heterogeneous outcome in the past. Our data indicate general safety and promote further refinements of the method and upcoming trials using progenitor cells.
