gms | German Medical Science

Objective: Replacement of striatal projection neurons by transplantation of fetal whole ganglionic eminence (WGE)-derived cell suspensions is a novel therapeutic approach for the treatment of Huntington's disease (HD). Here, we present an interim analysis on the safety, side effects and functional parameters of this approach in 15 HD patients.

Methods: Risk assessment is based on pharmacological safety involving immune rejection, tumor formation, disease transmission and side effects of immune suppression. Functional assessment involves motor scoring and cognitive tests. Patients enrolled in the trial received fetal WGE grafts. Fetal neural tissue was processed mechanically and injected by stereotactic implantation into up to six trajectories of the striatum bilaterally. 15 HD patients were transplanted bilaterally and 1 unilaterally, receiving tissue from 1–2 donors/side. Age at enrollment ranged from 31 to 53 years. No transmission of HIV, HBV, HCV or HTLV occurred.

Results: Fetal neurotransplantation was not associated with severe side effects in most patients. In a single patient, a bacterial cerebral infection (Staphylococcus spp.) was detected postoperatively. One patient who had suffered from chronic depression committed suicide and the brain was evaluated by immunohistochemistry. The most common side effects were associated with immune suppression. There was no case of graft overgrowth. One patient deteriorated shortly after withdrawal of immune suppression and improved after the administration of high-dose steroids. The time course of clinical changes after transplantation suggests that during the initial 6 months after transplantation, factors like the surgery or the onset of immune suppression result in a slight deterioration. Although most patients had decreasing functional benefits during the long-term course, two thirds of the patients improved or stabilized after a variable interval following surgery.

Conclusions: Clinically, WGE cell transplantation in HD can be considered as safe and feasible. The potential immunogenity of fetal neural grafts and the ongoing degeneration of the host brain might protract more substantial clinical beneficial effects in the long-term course of the disease. However, even a slowing down of the disease progression can be considered as therapeutically meaningful in this devastating disease. A more effective therapy may have to await a multimodal therapeutic approach combining e.g. cell replacement and neuroprotective strategies.