Inborn Errors of Metabolism

Propionic acidemia (PA) is a rare disease that is caused by an impaired ability to produce a critical enzyme necessary for mitochondria to supply energy. The condition can be life-threatening, so early diagnosis and treatment is critical to helping people living with PA.

PA symptoms often arise within the first year of an infant’s life, sometimes in the first days or weeks. These symptoms can include feeding difficulties, dehydration, lethargy, weak muscle tone, and delays in normal development.  Without treatment, the condition can lead to seizures, strokes, heart disease, and even, tragically, death.

The dysfunctional or missing enzyme that causes PA is called propionyl CoA carboxylase and plays a role in how cells convert food into energy. Disruption to this metabolic process results in two problems.  The first is a lack of energy in cells – an energy deficit – that hinders the ability of cells in vital tissue and organs in the body to function and grow properly. The second is a buildup of intermediates and unmetabolized fats and proteins that may become toxic at high levels.

We estimate that there are approximately 3,000 PA patients in the United States and Europe.

There are no approved therapies in the United States for propionic acidemia. Current treatment is based on a diet that severely limits intake of certain fats and proteins. Liver transplant or a combined liver-kidney transplant are recommended in severe cases. Transplant, however, is not curative, and the risks and lack of donors limit the widespread adoption of this approach.

The Imbria Solution

Substrate replacement is a promising therapeutic approach for the treatment of patients with propionic acidemia. In a study published in 2017, citrate replacement therapy for patients living with PA resulted in an 88% reduction in days hospitalized and a 75% reduction in emergency room visits over a two-year period.

We are developing IMB-202, a substrate replacement therapy, as a potential treatment for propionic acidemia that can be taken orally or with a gastric tube. It is intended to deliver therapeutic quantities of a specially designed citrate formulation in order to replenish missing chemical intermediates necessary for normal energy metabolism.