Case Report: Expanded Access Treatment of an Infantile Neuroaxonal Dystrophy (INAD) Patient with a Novel, Stabilized Polyunsaturated Fatty Acid Drug
INAD is an ultra-rare inherited neurological disorder. It begins within the first few years of life, and leads to a progressive impairment of movement, cognition, and vision. Its prevalence is extremely rare (<1:200,000), and it is inherited in an autosomal recessive pattern. Disease onset may start at 6 months of age with slowing of motor and cognitive development and regression of previously acquired skills. This is accompanied by roving eye movements, strabismus and nystagmus. Hypotonia is initially accompanied by preserved / brisk reflexes and is more obvious in the lower than the upper extremities. Death usually occurs between the ages of 5 to 10 years, often from loss of bulbar function leading to aspirational pneumonia. The genetic basis of INAD are mutations in the PLA2G6 gene (chromosome 22q12-q13) which encodes an 85 kDa group IV calcium independent phospholipase A2β (iPLA2β). The enzyme is responsible for the selective hydrolysis of the sn-2 ester bond of glycerophospholipids to release free polyunsaturated fatty acids (PUFAs). This is a critical housekeeping function in all cells membranes but in particular those exposed to high oxidative stress such as mitochondrial membranes in high energy tissues.