Triheptanoin Treatment Trial for Patients With Adult Polyglucosan Body Disease

Adult polyglucosan disease is a progressive neurogenetic disorder characterized by neurogenic bladder, progressive difficulty with walking, and sensory abnormalities in the lower extremities which typically present in the 4th or 5th decade of life. The pathogenesis of the disease includes the accumulation of intracellular polyglucosan bodies (amylopectin-like polysaccharides) in the peripheral nerves as well as the central nervous system cells and is often associated with brancher enzyme deficiency which causes improper glycogen formation. It is hypothesized that decreased glycogen degradation leads to energy deficit in the nervous system cells. Therefore, anaplerotic therapy may supply needed substrate to the citric acid cycle to correct the energy deficit. This intervention may slow, halt or reverse the progression of the disease, for which there is no effective treatment. The trial involves 18 subjects ingesting a diet supplemented with triheptanoin, a 7 carbon triglyceride or a placebo of vegetable oil at a dose of 1-2 g/kg/24 hours in a randomized crossover controlled double blind study. The study lasts one year with patients receiving triheptanoin for 6 mo and the placebo oil for 6 mo. Safety monitoring includes urine organic acids and acyl carnitine profile.

Inclusion criteria

• Confirmed diagnosis of APBD by the presence of mutations of the GBE1 gene in both alleles or brancher enzyme deficiency
• Willing and able to travel to Dallas TX
• Able to tolerate dietary oil
• Able to provide informed consent

Exclusion criteria

• Intercurrent medical conditions that would confound the assessment of efficacy, such as HIV or diabetes
• Patients who are wheelchair bound
• Patients deemed unsuitable for the study by the investigator