An 'n of 1' Conundrum: California's Gene Therapy Agency Wrestles with a Trial for an 'Extremely, Extremely' Rare Disorder

Precedent and policy questions come up on Wednesday at CIRM

Should California taxpayers spend $1 million for a clinical trial involving only one person and an extremely rare disorder known to affect only about nine persons in the world?

That’s the basic question this Wednesday before the California stem cell agency, whose current $4 billion is financing stem cell and gene therapy research for treatments for diseases ranging from heart ailments to autism. 

The single, unidentified patient involved in the trial is “a child with a severe neurodevelopmental disorder presenting with intractable epilepsy and severe neurodevelopmental delay,” according to the stem cell agency, officially known as the California Institute for Regenerative Medicine (CIRM). 

The cause is a rare variant in SCN2A, a gene that is critical to certain functions.  Changes in the gene can lead to pain, autism, visual impairment, epilepsy, intellectual impairment, orthopedic problems, speech deficits and more. 

The scientist seeking the funds for a “n of 1” trial is Joseph Gleeson of UC San Diego, who studies pediatric brain diseases and is director of neuroscience research at the Rady Children's Institute for Genomic Medicine in San Diego. The “n of 1” designation uses standard statistical jargon to show that the total number of patients (n) is no more than one. 

Gleeson’s application for $985,713 ran into a hitch last November when it was presented to CIRM directors for final ratification. It was the first clinical trial application involving only one patient to come before the CIRM board in 19 years.