Cell replacement therapy aims to replace cells lost to the disease process, with the rationale that they will re-innervate the host brain and repair the damage neural circuitry. In HD, the cells most affected are the medium spiny neurons (MSNs), so these are the target cells for cell replacement in HD. Cell replacement is only successful if the donor cells differentiate precisely into target cells (in this case, MSNs). In normal development MSNs differentiate within the part of the foetal brain called the ganglionic eminence (GE). Animal studies have shown that GE cells transplanted into the striatum of adult HD rodents can alleviate motoric and cognitive deficits. There is also pilot data suggesting that transplantation of human foetal GE cells can improve function in people with HD. However, the scarcity of foetal tissue of sufficient quality severely limits clinical application, quite apart from the ethical controversies surrounding this source. Thus, there is an imperative to identify a reliable renewable source of donor cells. Many potential sources exist, but most attention recently has been on deriving MSNs from human embryonic stem (ES) cells; an attractive potential donor cell source as they can be expanded in vitro, cryopreserved, and differentiated into mature somatic cells. Within the Repair-HD consortium, we are working to bring together the elements (optimisation of MSN differentiation protocols, GMP translation, rodent and primate transplant studies, and development of improved clinical assessment tools) required for clinical translation of ES-derived transplantation in HD.
- Neural transplant
- experimental medicine