Rare diseases are individually rare, but cumulatively common. Each disease affects only a small percentage of the population, but worldwide almost 10% of every person alive has a rare disease. That’s about 750 million people. Many of these diseases are monogenic (caused by a defect in a single gene) and can be severely debilitating and life-threatening. Historically, patient groups have been the principal advocates in raising awareness about these diseases, promoting national and international support. They have also driven relevant research programs, and in the field of genetic medicine these patient-advocate groups have been inordinately successful in driving monogenic diseases towards a viable therapy.
Simon Frost’s daughter Annabel has an ultra-rare neurological monogenic disease called Alternating Hemiplegia of Childhood, or “AHC”. The disease affects one in a million people, and the worldwide patient population is less than 1,000. AHC is characterized by sudden attacks of paralysis, seizures and spells of reduced consciousness like epilepsy, low muscle tone like cerebral palsy, movement problems like Parkinson’s, and neurodegeneration like Alzheimer’s.
Like many other patient-advocates, Simon decided to lead a community-driven initiative to find therapies rapidly. Unlike many others, he decided that to be effective he needed to learn the science of the disease. He studied the molecular and cellular mechanisms of AHC, and the phenotypic spectrum in patients. He developed and funded animal and cell models of the disease. He is leading a collaborative effort to provide whole genome sequencing to all patients, and natural history studies to gather longitudinal data. He has identified therapeutic options, especially focused on genetic medicines, and has developed and patented an AAV-mediated gene therapy for AHC. He and collaborating scientists have donated all intellectual property to the three largest AHC foundations in the world, with a goal to keep this genetic medicine cheap or free for patients.
In this talk, Simon discusses the challenges of understanding and diagnosing an ultra-rare disease, the constant fear of living with a “human timebomb”, and the immediate and unprecedented opportunities to address rare monogenic diseases as a community, as a nation, and as humankind.