The usual approach to understanding Mendelian disorders  is based on identifying the gene mutation responsible and expressing it in mouse. While productive for understanding gene functions this has led to many drugs effective in mouse but not in human. Why does this happen? For many patients with apparently Mendelian brain disorders the causative gene mutations are not known so that drugs aimed at an identified gene miss the target for most patients. Additionally, mouse models lack the genetic background upon which human gene mutations operate. We have developed a new technology for understanding brain disorders: patient-derived stem cells from the olfactory mucosa, the organ of smell in the nose that regenerates through the human lifespan. We use the heterogeneity among cells from multiple patients and controls to understand how gene mutations affect cell signalling pathways and cell functions, rather than concentrating on single genes and proteins. We derived olfactory stem cells from children with Ataxia Telangiectasia. These cells are metabolically normal until stressed by irradiation when they show expected deficits in DNA damage repair, which were abolished after correcting the genetic mutation. The AT patient-derived cells show deficits in neuronal differentiation. Hereditary Spastic Paraplegia is another familial disorder with multiple gene mutations causing similar clinical signs affecting upper motor neurons to the lower limbs. Olfactory stem cells from HSP patients with similar clinical phenotypes but different causative genetics had similar cellular phenotypes affecting intracellular organelle trafficking. These cells can be grown at sufficient scale for high throughput drug discovery.