AEB4104 Program – Homocyst(e)inase: Targeting homocysteine for classical homocystinuria
Classical homocystinuria is a rare disease resulting from the hereditary genetic deficiency in cystathionine beta synthase. It has been estimated to impact up to 1 in 344,000 people worldwide, however, its prevalence is significantly higher in some countries. The most common medical conditions associated with classical homocystinuria are cardiovascular complications including an increased risk of blood clots. Other symptoms include skeletal abnormalities, dislocation of the lens in the eye, and development and learning defects.
Currently available treatments for classical homocystinuria include high doses of vitamin B6 and betaine (N,N,N-trimethylglycine), the latter reducing homocysteine levels. Although these treatments are effective for some patients, responses fluctuate significantly due to the variations in the genetic mutation driving the disease. As a result, there exists an opportunity to develop a therapy that addresses the need of all patients by reducing blood homocystine levels back to the normal range.
AEB4104 is the lead enzyme in our discovery program to develop an engineered human enzyme designed to treat homocystinuria. We anticipate that enzyme replacement therapy with AEB4104 will degrade homocysteine and the oxidized form homocystine, returning blood levels to the normal physiological range. Normalization of homocystine/homocysteine levels may halt or slow the progression of the symptoms of the disease in these patients.