Natural History Study of CBS Deficiency

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Natural History Study of CBS Deficiency (ACAPPELLA Study)

Currently enrolling patients.

The goal of this study is to observe patients with Homocystinuria (CBSDH) upto 7 years to learn how their disease is managed under regular circumstances.

This study does not involve any investigational medications, but will provide information to researchers who are currently developing a medication to treat the disease.

The study has 5 main parts, all of which are provided free of charge to participants: bone exam (DXA scan), blood draws for important health tests, comprehensive eye exam, cognitive testing, and physical exams. To learn more about the study and see current locations, please click on this link

or contact

Travere Medical Information


In November 2020, Retrophin Inc. acquired Orphan Technologies, thus also acquiring OT-58 and their Natural History Study. Shortly after, Retrophin Inc. rebranded as Travere Therapeutics. You may see still publications and studies under the Orphan Technologies title, but it's important for people to know that Travere Therapeutics now retains all the information regarding those studies.

Why are Natural History Studies Important to the Homocystinuria Community?

Like most rare diseases, Homocystinuria is not well-studied and poorly understood by the medical community. Researchers and biotech companies rely on natural history studies for a baseline understanding of the disease so they can can develop better therapies, which would need to go through clinical trials in order to be approved.

While Classical Homocystinuria does have a natural history study it's outdated. The last natural history study was published in 1985 based upon 629 patient data collected from published papers and questionnaires. For reference, b6, b12, and folic acid were just starting to be regularly used for management of classical homocystinuria. Now we have the low protein (methionine more specifically) diet, medical formula and Cystadane. With improved therapy, our baseline understanding has changed and needs to be reassessed to reflect so.

You can learn more about natural history studies, patient registries, and the drug development pipeline by visiting our YouTube Channel and watching our webinar on Roadmap to Innovation for HCU.

Click here to view the presentation

Natural History Study: A Patient Experience

Behind the Scenes: Why I chose to join the Orphan Technologies Natural History Study.

The patient who shared their experience will remain anonymous to protect the integrity of the data collected by the Natural History Study for Cystathionine Beta Synthase (Classical Homocystinuria).

September 2017
On an early fall morning I sat in the activity room at work. There was a lot on my mind that morning, but the thing that was pushed to the forefront of my mind was the Orphan Technologies (now supported by Travere) Natural History Study for Homocystinuria. I had been considering it and thought about joining, but obligations at work made me question my decision. While I was sitting in there, I told my coworker Lisa about wanting to go to Atlanta. After she responded I decided to go ahead and join the study.

October 2017
As a patient I was genuinely frustrated with the lack of treatment options and the cost of the medications, so I sent an email to a contact about joining. The person responding pointed out that I was not in close proximity to a study location. The fact that this disease is so rare and that treatment options are so limited is part of why I chose to go ahead despite the distance it would take to get to Atlanta. I had experience traveling for medical care so traveling to a study visit was not an inconvenience, but an opportunity to give back. It was also a chance to travel and to get to know a place I had never been to. Before I joined the study, I had only been there in passing when flying and leaving out of Hartsfield- Jackson Airport, also known as ATL. After the first visit what was once foreign became familiar.

March 2018
March 9, 2018, was my first study visit, which was also known as the baseline visit. At this visit they started with blood work. The visit also included a physical where we discussed my medications and the way Homocystinuria has manifested. During this time, I handed in a three-day diet record which requires you to record everything you eat and drink leading up to the visit. The National Institutes of Health (NIH) Toolbox is a series of cognitive tests which was another part of the visit. Later that afternoon, I had an eye appointment where my eyes were dilated and evaluated. A dual -energy x-ray absorptiometry, also known as a DXA/DEXA scan was also performed to assess for osteoporosis.

September 2018
Six months later I went back Atlanta, or more specifically Emory. This time the visit was much shorter and consisted of blood work, a physical and the NIH Toolbox. That is a part of every appointment. Once a year they do the DEXA scan, and eye appointment. Through participating I know I have contributed and am grateful for the opportunity.

Note* Since joining this study, Orphan Technologies has been acquired by Travere Therapeutics


Publications regarding the Natural History Study of CBS Deficiency

August 24, 2023

Travere Therapeutics to Present Abstracts at the Society for the Study of Inborn Errors of Metabolism Annual Symposium 2023

Travere Therapeutics presented clinical data from the Phase 1/2 COMPOSE Study of pegtibatinase, a novel investigational enzyme replacement therapy being evaluated for the treatment of classical homocystinuria (HCU), at the Society for the Study of Inborn Errors of Metabolism (SSIEM) Annual Symposium in Jerusalem, Israel, August 29 – September 1, 2023.

The Company and its collaborators also presented analyses on its prospective HCU natural history study, the prevalence of HCU, and the burden of HCU from the patient perspective highlighting the devastating nature of this rare metabolic disease over patients’ lifetimes and underscoring the urgent need for new treatments. In addition, the Company presented data on the clinical burden of HCU and the relationship between total homocysteine (tHcy) and clinical outcomes, which has been recognized as one of the highest-ranked posters at SSIEM.

August 25, 2022

Travere Therapeutics to Present Abstracts at the Society for the Study of Inborn Errors of Metabolism Annual Symposium

  • Population-based Incidence Estimates of Classical Homocystinuria Using the Genome Aggregation Database (gnomAD)

  • A Longitudinal Study of Cognitive Function in Classical Homocystinuria Demonstrates Distinct Deficits in Inhibitory Control

  • Insights from the First Genetic Evaluation of a Longitudinal Natural History Study in Classical Homocystinuria (HCU)

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