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Celiprolol.png

Celiprolol

A beta blocker used in vEDS patients in Europe.

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Enzastaurin

A PKCβ inhibitor studied in vEDS mice at Johns Hopkins.

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What is Celiprolol?

Celiprolol is in a family of drugs called ‘beta-blockers’. In general, these medications lower your heart rate and decrease your blood pressure. Many blood pressure reducing medications have been considered for use in vEDS. This includes other beta-blockers as well as angiotensin processing blockers or receptor blockers(1); both of these are readily available in the United States. The goal with any of these medications is to reduce your blood pressure to the normal, or low-normal blood pressure range(1).

What makes celiprolol unique compared to any other beta-blockers or other blood pressure medicine is that it was the only medication that has been studied in a randomized clinical trial for vEDS, prior to the FDA trial from Aytu Biopharma (2). This trial asked the question, "Compared to getting no treatment at all, does using celiprolol decrease the number of vascular events?" This trial is known as the BBEST Trial, which stands for ‘Beta-Blockers in Ehlers-Danlos Syndrome Treatment’(2). It is because of this trial that some physicians, particularly those in European countries such as France, are now recommending the use of celiprolol for the treatment of vEDS.

Celiprolol

The Beta-Blockers in Ehlers-Danlos Syndrome Treatment (BBEST) Trial

In 2010, researchers in Europe published a landmark study known as the BBEST trial. The study analyzed the use of a medicine called celiprolol to see if it could help improve outcomes in patients with vascular Ehlers-Danlos syndrome. After this landmark trial, celiprolol became the standard of care for vEDS in France and other European countries. In April 2019, the researchers responsible for the study published new results, which tracked vEDS patients on celiprolol for up to 17 years.

Should I be on celiprolol?

There is some debate within the community of doctors that study and treat vascular EDS. Some doctors feel that since celiprolol is the only medicine that has been studied in vEDS (and showed a benefit in that study), that if you can be on celiprolol you should be. Other doctors feel that the celiprolol study had flaws and that there are other beta-blockers available in the United States already which can work just as well. Management of your vascular Ehlers-Danlos syndrome (including choice of medications) should be discussed with your treating physician.

Where can I get celiprolol?

Currently celiprolol is not available in United States, as it is not an FDA approved drug.  There is a pharmaceutical company named Acer Therapeutics that is considering a trial to get FDA approval for the drug in the United States.

While the drug can be accessed through online pharmacies, those pharmacies require a written prescription from your physician, who may or may not be comfortable prescribing the drug ahead of FDA approval. If you are considering celiprolol therapy, you should discuss this and other treatment options with your physician.

When will celiprolol be available in the United States?

Acer Therapeutics, a pharmaceutical company based in Massachusetts, is currently considering pursuing FDA approval of celiprolol for vascular EDS. Acer Therapeutics is currently considering a study within the next few years that could make the drug available in the US. We will keep our subscribers informed of their progress (subscribe to our emails at the bottom of this page).

Enzastaurin
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What is Enzastaurin?

Enzastaurin is a well characterized PKCβ inhibitor that has been evaluated in over 50 clinical trials, with more than 3300 patients. This includes a Phase 3 study of nearly 500 patients with 3 years of enzastaurin treatment.

The treatment inhibits certain pathways that researchers believe may be linked to arterial rupture in vEDS patients. By inhibiting the signaling pathway, the treatment may potentially reduce the number of vascular events, which was the case in studies of animal models at Johns Hopkins.

Study of enzastaurin at Johns Hopkins

In 2020, Johns Hopkins researchers published the results of a study of enzastaurin (as well as other treatments) in a vEDS mouse model in the Journal of Clinical Investigation. The study found that treating the mice with enzastaurin reduced the risk of death from aortic dissection, with 80% of enzastaurin-treated vEDS mice surviving after 40 days of treatment compared to only 50% of untreated vEDS mice. These results were significant and provided the foundation for the study of enzastaurin in an clinical trial for potential FDA approval of the treatment in humans. Learn more about the research on our clinical trials page.

A clinical trial of enzastaurin

Enzastaurin has been evaluated as a treatment for other conditions in over 50 clinical trials, with more than 3,300 patients. This history may give some comfort to patients regarding the safety profile of the treatment; however, it has never been studied in vEDS.

Aytu Biopharma is pursuing an FDA clinical trial to demonstrate the effectiveness of the treatment in vEDS in 2022. Learn more about the study and how to enroll on our clinical trials page.

Sources:

  1. Byers PH, Belmont J, Black J, De Backer J, Frank M, Jeunemaitre X, Johnson D, Pepin MG, Robert L, Sanders L, Wheeldon N.  2017.  Diagnosis, natural history and management in vascular Ehlers-Danlos syndrome.  American Journal of Medical Genetics Part C (Seminars in Medical Genetics). 175C:40-47.

  2. Ong KT, Perdu J, De Backer J, Bozec E, Collignon P, Emmerich J, Fauret AL, Fiessinger JN, Germain DP, Georgesco G, Hulot JS, De Paepe A, Plauchu H, Jeunemaitre X, Laurent S, Boutouyrie P. 2010. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: A prospective randomized, open, blinded-endpoints trial. Lancet 376: 1476-1484.

  3. Caitlin J Bowen, Juan Francisco Calderón Giadrosic, Zachary Burger, Graham Rykiel, Elaine C Davis, Mark R Helmers, Kelly Benke, Elena Gallo MacFarlane, Harry C Dietz.  2020 Feb 3.  Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome.  The Journal of Clinical Investigation. 175C:40-47.

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