Combination therapy for Huntington's disease; feasibility studies for transplantation of hESC-derived cells expressing the apical domain of CCT1.

Funding Type: 
Early Translational IV
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Huntington’s disease (HD) is a devastating degenerative brain disease that inevitably leads to death. Because it is genetically dominant, children of patients have a 50% chance of inheriting HD. The prevalence of 1 in 10,000 does not fully reflect the large societal and familial costs of HD, which requires extensive caregiving. Symptoms include uncontrolled movements, difficulty carrying out daily tasks or continuing employment and psychiatric manifestations such as depression, which progress inexorably for 15-20 years. Onset is typically in mid-life, however children are also affected, and current treatments only address some symptoms and do not change the onset or course of the disease. Therefore, a completely unmet medical need exists. Human embryonic stem cells (hESCs) offer a possible long-term treatment approach that could relieve the tremendous suffering of patients and their families. Our proposed feasibility studies will transplant stem cell lines programmed to deliver a neuroprotective protein that can unravel and clear the mutant HD protein in the brain. We have assembled a team of investigators and consultants with a goal of establishing the feasibility of using the proposed stem cell-derived development candidate to alter the course of disease following transplantation in HD mice These preclinical studies will provide information for future development of this stem cell-derived candidate as a potential treatment of HD.

Statement of Benefit to California: 

Disability and loss of earning power and personal freedom resulting from Huntington's disease (HD), the 3rd most prevalent neurodegenerative disease, is devastating and creates a financial burden for California. Individuals are struck in the prime of life, at their most productive and with highest earning potential. As HD progresses they require institutional care at great financial cost. Therapies using human embryonic stem cells (hESCs) have the potential to change the lives of hundreds of patients and families; thousands could benefit. This early translation feasibility grant will fund a comprehensive, systematic evaluation of hESC-derived cell lines secreting a neuroprotective protein, to define the approach’s feasibility and develop a candidate viable treatment option. Because HD is entirely genetic and the mutation known, a diagnosis can be made with certainty. Clinical applications of hESCs may provide insights into other brain diseases not caused by a single, known mutation. Future benefits to the citizens of California include: 1) discovery and development of new treatments for HD, with application to other more prevalent diseases ; 2) transfer of new technologies and intellectual property to the public realm, resulting in revenues and possible creation of new biotechnology companies; and 3) reductions in extensive care-giving and medical costs. We anticipate that the return to the State in terms of revenue, health benefits and job creation will be significant.