Developing a drug screening platform for anorexia nervosa with patient-derived neurons

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

Anorexia nervosa (AN) is a complex developmental illness that affects 0.3-0.7% of women across the nation. Although anorexia has the highest mortality of any psychiatric illnesses, we do not have FDA approved treatments. Symptoms of anorexia include extreme food-induced anxiety and reduced intake of food resulting in weight loss to the point of emaciation or death. Patients with anorexia face debilitating medical consequences during their illness, many of which can become long-lasting, such as failure to produce blood cells, failure of the kidneys, osteoporosis and reproductive failure. Alleviating symptoms has the remarkable potential to reduce mortality and morbidity. Genetic studies show that up to 80% of the risk of becoming ill with anorexia is heritable. Our recent data identify specific changes in the DNA sequence that contribute to the risk of becoming ill and provide much needed guidance on which molecular pathways to target with new treatments. However, the lack of human cellular models has blocked any progress thus far. Potential alternatives such as mouse models do not have the symptoms associated with this human illness. Generating human neurons from skin fibroblasts through stem cell technology offers a great opportunity to develop a drug screening platform to rapidly test thousands of drugs. This proposal establishes such a screening system where we will test promising leads from the clinic that target human genetic pathways implicated in anorexia.

Statement of Benefit to California: 

Anorexia nervosa has the highest mortality of any psychiatric illness and results in significant death and disability within California. Anorexia nervosa is poorly understood and effective treatments are lacking with devastating consequences for patients and their families. Our innovative approach that combines stem cell technology and genetics to accelerate drug discovery offers a remarkable opportunity to make advances in treatment that was not previously possible. Our approach will not only relieve the enormous burden on patients and families but also on the healthcare resources across California. Stimulating drug discovery technologies will also create jobs through new biotech and engineering ventures that are essential to keep California's economy strong.