Chemistry: Generation 2+
ION283 is an investigational antisense medicine designed to reduce the accumulation of glycogen by inhibiting the production of brain glycogen synthase type 1 (GYS1), the enzyme that makes glycogen in the brain. Mutations that are the genetic cause of Lafora disease (LD) result in the accumulation of excess glycogen and result in the formation of Lafora Bodies in the brain and spinal cord, which results in neurodegeneration. In animal models of LD, reduction of GYS1 reduced glycogen accumulation and prevented the formation of Lafora Bodies and neurodegeneration.
About Lafora Disease
Lafora disease (LD) is an inherited and very severe epilepsy syndrome. Although children are born with LD, the disease does not manifest itself until adolescence when seizures begin.
LD is characterized by a progressive increase in intensity of seizures, a rapid cognitive decline (dementia) and motor incoordination (ataxia). Patients who suffer from this devastating disease have difficulty walking, speaking and eating and will eventually become wheelchair bound, and lose the ability to speak and feed themselves. Lafora patients typically die within 10 years.
LD is autosomal recessive disease caused by mutations in the laforin or malin genes. The underlying pathology is the result of glycogen accumulation in neurons and glial cells that form toxic Lafora Bodies. Currently, there is no disease-modifying therapy and seizures are poorly managed with anti-epileptic drugs.