Nav: Home

New hope for rare disorder

July 26, 2018

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent painful swellings of the skin and mucous membranes. Without treatment, patients' quality of life is noticeably compromised: Angioedema may not only be disfiguring; in the gastrointestinal tract it may lead to severe abdominal colic ad in the upper airways it can even be fatal if left untreated. The frequency of angioedema attacks is unpredictable and varies from patient to patient; swellings may occur up to several times a week. The disorder affects about one to two in a hundred thousand people.

A new drug has been developed to help prevent attacks of hereditary angioedema and at the same offer the patients a convenient administration. It has now been investigated in an international study performed at over 26 university facilities in Europe, Canada and Australia. The results were clear: the drug is highly effective with regard to attack prevention and improvement in quality of life while offering a convenient oral administration. Dr. Emel Aygören-Pürsün, specialist in internal medicine at the Division of Oncology, Hematology and Hemostaseology at the Department for Children and Adolescents of the University Hospital Frankfurt, served as the principle investigator of the study. "Hereditary angioedema is a condition that may be associated with lifelong impairment. With this fundamentally new development, we may reduce HAE- attacks and consistently improve our patients' quality of life," explains Dr. Emel Aygören-Pürsün. The HAE competence centre at University Hospital Frankfurt is one of the leading institutions nationwide for patient care and the clinical development of therapies for hereditary angioedema. Professor Thomas Klingebiel, Director of the Department for Children and Adolescents, underlines the significance of the results: "Pioneering patient care and cutting-edge clinical research - these are what University Hospital Frankfurt stand for." The results of the study have now been published in the renowned New England Journal of Medicine.

Genetic disorder leads to uncontrolled swellings

For most cases of hereditary angioedema, the underlying cause is a congenital deficiency or dysfunction of what is known as C1-inhibitor. As a result of C1-inhibitor deficiency, plasma levels of bradykinin increase, a peptide which locally increases the permeability of the smallest blood vessels.

The central role of bradykinin in the development of angioedema attacks is well established for hereditary angioedema. Attacks of angioedema in patients with hereditary angioedema are related to the action of bradykinin, whose generation is closely linked to another plasma protein, called kallikrein. If kallikrein is active, then bradyinin generation is the result. The inhibition of kallikrein should therefore be a suitable measure for prophylaxis of angioedema attacks.

Therapeutic breakthrough in the form of capsules

So far, the prevention of angioedema attacks in hereditary angioedema was bound to medication that required injections. Although drugs were also available as tablets, these proved either ineffective or were not licensed in many countries. In addition, some of them led to severe side effects and could not be administered to children or during pregnancy.

The new drug BCX7353 tested in the study is a synthetic small molecule that acts as a specific kallikrein inhibitor and is administered as capsules. The aim of the development was to achieve an effective prophylaxis with the distinct advantages of an oral administration yet without the side effects of the oral preparations used previously.

Study methodology

During the study, 77 patients were randomized to groups of four different dose levels or placebo. They took the respective dose once daily for 28 days. The patients noted in their diaries the frequency, localization and severity of the attacks; quality of life was recorded at the beginning and the end of the study using a validated questionnaire. Changes in the frequency of the attacks were investigated, as were the side effects from the treatment and the impact on patients' quality of life.

Convincing results

The results were positive: With a daily dose of 125 mg and higher, a significant reduction of angioedema attacks was demonstrated. Patients who took 125 mg of BCX7353 per day even experienced a reduction in the frequency of their attacks of almost 75 percent compared to placebo; over 40 percent of patients in that dose group remained completely free of attacks during the study. Also the increase in quality of life was most evident for the 125 mg dose; in addition, not only the number of peripheral attacks was reduced in this group but also those in the gastrointestinal tract. Moreover, the side effects of this dose ranged mild.

Overall, the study was able to clearly corroborate the efficacy of BCX7353 and at the same time provide information about the ideal dosage and tolerability of the new drug. Further studies will now be necessary to verify the efficacy and safety with its long-term administration.
-end-
Publication: Aygören-Pürsün, E., et al, Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema, New England Journal of Medicine 2018;379:352-62. DOI: 10.1056/NEJMoa1716995.

Further information: Dr. Emel Aygören-Pürsün MD, Internal Medicine and Hemostaseology, Division of Oncology, Hematology and Hemostaseology, Department for Children and Adolescents, University Hospital Frankfurt, Tel. +49 (0)69- 63 01 63 12 / 63 01 63 44, aygoeren@em.uni-frankfurt.de

Current news about science, teaching, and society in GOETHE-UNI online (http://www.aktuelles.uni-frankfurt.de)

Goethe University is a research-oriented university in the European financial centre Frankfurt The university was founded in 1914 through private funding, primarily from Jewish sponsors, and has since produced pioneering achievements in the areas of social sciences, sociology and economics, medicine, quantum physics, brain research, and labour law. It gained a unique level of autonomy on 1 January 2008 by returning to its historic roots as a "foundation university". Today, it is among the top ten in external funding and among the top three largest universities in Germany, with three clusters of excellence in medicine, life sciences and the humanities. Together with the Technical University of Darmstadt and the University of Mainz, it acts as a partner of the inter-state strategic Rhine-Main University Alliance. Internet: http://www.uni-frankfurt.de

Publisher: The President of Goethe University Editor: Dr. Anne Hardy, Referee for Science Communication, PR & Communication Department, Theodor-W.-Adorno-Platz 1, 60323 Frankfurt am Main, Tel: (069) 798-13035, Fax: (069) 798-763 12531.

Goethe University Frankfurt

Related Side Effects Articles:

What if we could design powerful drugs without unwanted side effects?
The paper describes how to minimize or eliminate side effects in drugs that target G protein-coupled receptors.
Variation in how side effects are reported clouds drug safety
University of Colorado Cancer Center study finds significant variation in how drug side effects are reported, potentially making some drugs seem safer or less safe than they really are.
New drug can ease the side effects of medication against severe depression
Today, severe depressions require a high dose of antidepressants. However, the high dose may also cause serious side effects.
University of Cincinnati research looks at side effects for pediatric medications
Dr. Jeffrey Strawn, associate professor in the Department of Psychiatry and Behavioral Neuroscience at the University of Cincinnati College of Medicine, and Jeffrey Mills, associate professor in the Department of Economics at the UC Lindner College of Business, published a study in the Journal of the American Academy of Child & Adolescent Psychiatry looking specifically at side effects that impact children and adolescents being treated for anxiety disorders and obsessive-compulsive disorder (OCD).
Reducing the side-effects of prostate hormone therapy with exercise
A prescription of short-term exercise for patients with advanced prostate cancer could help to reduce the side-effects of hormone therapy, according to new research.
The gut may be the ticket to reducing chemo's side effects
In a new study, scientists observed several simultaneous reactions in mice given a common chemotherapy drug: Their gut bacteria and tissue changed, their blood and brains showed signs of inflammation, and their behaviors suggested they were fatigued and cognitively impaired.
Nerve cell protection free from side effects
The hormone erythropoietin (Epo) is a well-known doping substance that has a history of abuse in endurance sports.
Proton therapy for cancer lowers risk of side effects
Proton therapy results in fewer side effects than traditional X-ray radiation therapy for many cancer patients, according to a new study led by Washington University School of Medicine in St.
What are the neurological side effects of CAR T-cell therapy?
A team at Brigham and Women's Hospital recently cataloged the neurological symptoms of patients who had received CAR T-cell therapy to better understand its neurotoxic side effects.
Using 3D models to reduce side effects of radiotherapy
The debilitating side effects of radiotherapy could soon be a thing of the past thanks to a breakthrough by University of South Australia (UniSA) and Harvard University researchers.
More Side Effects News and Side Effects Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Graham
If former Minneapolis police officer Derek Chauvin's case for the death of George Floyd goes to trial, there will be this one, controversial legal principle looming over the proceedings: The reasonable officer. In this episode, we explore the origin of the reasonable officer standard, with the case that sent two Charlotte lawyers on a quest for true objectivity, and changed the face of policing in the US. This episode was produced by Matt Kielty with help from Kelly Prime and Annie McEwen. Support Radiolab today at Radiolab.org/donate.