Homocystinuria

Researchers are looking for a better way to treat people living with classical homocystinuria (HCU), a rare inherited condition. It is caused by changes in the cystathionine beta-synthase (or "CBS") gene and prevents an enzyme from working correctly in the body. This enzyme helps break down homocysteine, which is produced when the body processes methionine from protein-containing foods. This helps keep homocysteine and methionine at healthy levels. When this enzyme is not working, homocysteine and methionine build up in the blood and then spread into different tissues of the body and stop these body tissues from working normally. People living with HCU can experience problems with their vision, bones, blood vessels, thinking, learning, and memory. Available treatments for HCU include a low-methionine diet (typically achieved by limiting protein-containing foods), a methionine-free protein supplement to help meet daily protein needs, and betaine (Cystadane®). These treatments are either not sufficient or are hard to take for many patients. Pegtibatinase was designed by researchers to act like the CBS enzyme, which is missing or not working properly in people living with HCU. Researchers are studying whether adding pegtibatinase to standard treatment can lower homocysteine levels. Researchers want to learn how safe and effective pegtibatinase is, how it moves through and affects the body, and how it may affect the daily lives of people with HCU. The study plans to enroll participants from the US, Australia, Belgium, France, Germany, Ireland, Italy, Poland, Portugal, Qatar, Saudi Arabia, Spain, Turkey, and the United Kingdom. Many study visits may happen at home, depending on where you live and local regulations. Some visits may include a home nurse and telemedicine appointments with the study doctor.

Researchers are looking for a better way to treat people who have classical homocystinuria (HCU), a rare condition that is passed down by parents (or "genetic condition"). It is caused by changes in the cystathionine beta-synthase (or "CBS") gene and prevents an enzyme from working correctly in the body. This enzyme breaks down a substance called homocysteine (from dietary methionine found in protein) and keeps both homocysteine and methionine at normal levels. When this enzyme is not working, homocysteine and methionine build up in the blood, which spreads into different tissues of the body and stops these body tissues from working normally. People with HCU can experience problems with vision, bones, blood vessels, and cognitive function (the ability to think, learn, and remember). Treatments available for HCU, such as a low protein diet and betaine (Cystadane®), help reduce homocysteine levels. The diet is a low methionine diet and a methionine-free protein supplement (a product that provides extra protein to help meet daily protein needs). These treatments are either not sufficient or are hard to take for many patients. Pegtibatinase was developed by scientists to be a version of the CBS enzyme that can be given to people with HCU. Researchers believe that giving pegtibatinase to people with HCU already getting medical treatment (or "standard of care") may reduce their homocysteine levels. This study is split into 7 different groups getting different amounts of drug. The first 6 groups have already finished the study. Group 7 plans to enroll participants from the US (virtual and in-person), France, and Qatar.

Patients, parents of young / handicapped patients, and experts will be interviewed to collect contents relevant for HrQoL in CBS deficiency. Based on these data, a questionnaire will be developed and tested for comprehensibility in patients and parents of young / handicapped patients. A final questionnaire version will be tested for psychometric criteria including validity and reliability.