Introduction Cell transplantation is a potential therapeutic for people with Huntington’s disease (HD). Medium spiny neurons are primarily lost in HD therefore transplanting a healthy source, from foetal tissue or stem cells, into the diseased striatum provides a method of brain repair. Following transplantation pre-clinical studies have suggested the recipient must ‘learn to use the graft’ through striatally targeted behavioural training to encourage graft integration to the host tissue.
Aims Given the variable procedures applied post transplantation in people with HD, this translational project aims to:
Understand the optimal time to begin training the graft using a rat model of HD (Exp 1).
Develop an affordable, quantitative assessment for people with HD that that can efficiently track functional improvements that manifest post transplantation (Exp 2).
Method Exp 1: Rats were pre-trained on a striatally dependent skilled reaching task. After receiving unilateral striatal lesions, a subset of rats received transplants of rat foetal tissue. Rats were retested on the same task at either two or twelve weeks post-graft.
Exp 2: A novel grasping and dexterity multi-task assessment called the Moneybox test (MBT) was developed and tested alongside commonly used outcome measures in people with all stages of HD.
Results Exp 1: Pre-clinical results will help us understand when to initiate training and if early training is beneficial or detrimental to graft function post transplantation.
Exp 2: The MBT is highly sensitive to functional impairment across all stages of HD (P < 0.001) and more closely correlates with gold standard HD measures compared to other commonly used outcome measures.
Conclusion Understanding when to initiate training will improve graft functionality and developing sensitive outcome measures to identify striatal dysfunction will ultimately move this treatment closer to clinical application.
- Cell transplantation
- outcome measures
- pre-clinical behaviour