Research

Scientists are fascinated by Dupuytren’s, and many of them are trying to unravel the mystery of why patients develop these problems. Here is a list of some of the research projects going on at the moment, it is unlikely to mention all research because we may not have permission to mention ongoing projects or we may not know about them.  The order in which they are presented is arbitrary and does not in any way indicate our support or success in the field.

For trials and studies that patients may join in, please go to the Trials page.

To see our webinar on research being done in the UK, click this link

United Kingdom

RIDD_Logo_VFINAL_0At the Kennedy Institute of Rheumatology of the Oxford University, UK, a team led by Professor Jagdeep Nanchahal BSc, PhD, MBBS, FRCS, FRSC(plast) is doing clinical trials for a revolutionary type of treatment. Patient recruitment has finished now in Oxford and Edinburgh, and has moved to Groningen, the Netherlands to inculde a different population demographic. 

Dr Anne Francis RIDD trial manager provided us with this explanation:

  The RIDD trial is investigating whether injections of anti-TNF can help early stage Dupuytren’s disease. The trial has two parts- the first part which is now completed was a dose response study in which patients with moderately advanced disease with finger contracture, who are due to have surgery to remove the diseased tissue, were given an injection of either anti-TNF or a placebo. The removed tissue is now being examined at the labs in Oxford to see the effects of anti-TNF at different doses on the Dupuytren’s cells. The second part of the trial is looking at whether anti-TNF slows or prevents the progression of Dupuytren’s in patients with early stage disease. The progression of the disease will be followed for 18 months and the trial team will be looking to see if people who have received anti-TNF therapy slows or prevents the progression of the Dupuytren’s in patients with early stage disease. Anti-TNF therapies have a well-established safety profile and have been used worldwide for around twenty years to treat disorders such as rheumatoid arthritis and Crohn’s disease.

The RIDD trial is a translational study, meaning that it has been developed using knowledge gained from lab-based experiments. These experiments have shown that Dupuytren’s nodules contain high numbers of cells called myofibroblasts, which normally help repair wounds by producing proteins that bridge the wound and then contract to pull the wound together. In Dupuytren’s disease these scaffolding proteins develop into fibrous cords just under the skin of the palm. The contractions of the myofibroblast cells then pull on the cords and curl the finger irreversibly towards the palm. Using tissue samples collected during surgery, Professor Nanchahal’s group have shown that TNF (tumour necrosis factor) produced by inflammatory cells causes precursor cells to change into myofibroblasts – but only in people with Dupuytren’s disease. They have also found that drugs which block TNF reduce the activity of the myofibroblast cells. These results led to the development of the RIDD trial and the lab work is continuing to further explore the mechanisms of the disease. All of the lab work is made possible by the donation of Dupuytren’s tissue by patients having surgery.

You can find out more about the research group on their website. The protocol is published online here.

Professor Nanchahal explains more about the trial on our webinar.

The RIDD trial is registered on the European Clinical Trials database (EudraCT:2015-001780-40) and ClinicalTrials.gov.

The same medication is also being tested for Frozen Shoulder.

(ongoing January 2020)

At the University of Liverpool a team led by Dr Elizabeth Laird is studying the development of fibrosis (excessive collagen production) in Dupuytren’s Disease. The work is supported by the Clinical Research Network (North West Coast), by surgical teams at the Royal Liverpool and Broadgreen University Hospital Trust (RLBUHT) and Warrington and Halton Hospitals NHS Trust, and by donations of tissue from patients undergoing hand surgery, without whom this research would not be possible.

In one study the group are deciphering the protein ‘fingerprint’ in Dupuytren’s Disease using proteomics technology. The aim of the study is to profile the proteins present and being newly synthesized in fibrotic Dupuytren’s tissue, which is important to completely understand the molecular differences between proteins in Dupuytren’s tissue and those in normal non-pathologic tissue. The hypothesis of the study is that the continual production of an altered profile of proteins in Dupuytren’s tissue may be the underlying cause of recurrence of Dupuytren’s contracture following surgical treatment. The Dowager Countess Eleanor Peel Trust granted funding for proteomics analysis for this study.

The group is also studying collagen production in Dupuytren’s Disease, specifically an abnormal form of collagen that can not be degraded. This particularly noxious abnormal collagen persists in the thickened tissue preventing the disease from resolving naturally. The group are investigating cell types and molecules responsible for abnormal collagen production. Dupuytren’s tissue has been shown to be home to several biologically active molecules including cytokines and microRNAs. The team are using molecular activation and inhibition strategies to determine which molecules drive abnormal collagen production. The aim of this study is to determine if existing therapies could be adapted to treat Dupuytren’s Disease, prevent recurrence and to develop new strategies to target fibrosis. This work is funded by the Medical research Council and Arthritis Research UK.

View an explanation of this research on our webinar

( Ongoing 2020)

In Oxford University Professor D Furniss does research into the molecular genetics of Dupuytren’s. His team works closely with other groups such as the team of Prof Werker in Groningen. They do whole genome studies to determine the inheritance of Dupuytren. To date 26 genes have been found that play a role, and 80% of the disease is said to be due to genetics.

He explains more about the research in our webinar.

 

As of 2018 Mr Rodrigues continues the research he started with the aid of an NIRH post-doctorate at NDORMS, Oxford.

This will be a five year program of training and research to further refine outcome measurement in Dupuytren Disease, and to better harness UK national outcome data in the UK National Hand Registry delivered by the BSSH.

(updated January 2018)

The Netherlands

 

The Team working under Prof Paul Werker in the University of Groningen, the Netherlands has provided us this information about their research. We received this description of their research from Dieuwke Broekstra:

During the past years, the Department of Plastic Surgery of the University Medical Centre Groningen initiated a large study on the genetic background of Dupuytren disease. This study was done in cooperation with medical centres in the Netherlands, England and Germany.  Several genes were identified to be involved in Dupuytren disease, and we found that the Wnt signalling pathway plays an essential role in the disease pathology. This research project has been continued, focussing on cell biology processes, including the Wnt pathway, that form the origin of Dupuytren disease and associated fibromatoses. This leads to a better understanding of the pathology, and provides valuable information on possible starting points for future treatment options. Recently a new PhD project was started, focussing on genetic variants in Dupuytren’s Disease in general, and the functional implications of the NEDD4 locus more specifically.

Additionally, the Department of Plastic Surgery is also involved in research about epidemiological aspects of Dupuytren disease. For instance, we determined the prevalence of Dupuytren disease in the general population aged over 50 in the city of Groningen, which was 22%. Furthermore, we investigated disease patterns and started a study to follow the course of Dupuytren disease. The latter is a longitudinal cohort study including 262 Dupuytren patients with various disease stages. Every 6 months, the hands of the participants are examined to record the disease progression in detail. Eventually, the data of this study will be used to identify factors that predict the course of the disease. Further epidemiologic studies that are conducted in cooperation with the University of Oxford, comprise the analysis of routinely collected data (CPRD) to evaluate the incidence of Dupuytren’s disease surgery, and finding predictors for surgery.

Next to that, our department also focusses on the anatomy of Dupuytren disease. Despite the fact that the condition has first been described in the early 17th century, the patho-anatomy is largely unexplored. This knowledge can contribute to a successful treatment, since many treatment options require a detailed knowledge of the anatomy.

Finally, our department has been involved in various research projects concerning the surgical treatment of Dupuytren disease. It was found that limited fasciectomy (resection of diseased tissue) provides a more durable result than percutaneous needle fasciotomy (dissection of the cord with a needle). However percutaneous needle fasciotomy also demonstrated several advantages compared to limited fasciectomy: quick recovery and a low chance of complications. New innovations in treatment and diagnosis of Dupuytren disease are also subject of research. For instance, we recently started a research project to determine the added value of ultrasonography in prevention of complications that can occur after treatment. In addition, we are investigating whether it is possible to predict Dupuytren disease progression using ultrasonography.

(updated January 2018)

Belgium

 Leuven RU

Dupuytren-Fonds, Leuven University Hospitals, Belgium. Text submitted by Prof Dr Ilse Degreef.

On November 17th 2016, we celebrated the inauguration of the Dupuytren funding organisation, an initiative of Prof Dr Ilse Degreef and Prof Dr  Luc Smet at Leuven University.

With this foundation, both clinical researchers and patient organisations will work together to improve treatment outcome and patient satisfaction in Dupuytren disease. Clinical hand practice at the academic centre is focussed on Dupuytren treatment and the improvement of it. With a multi-disciplinary approach, we aim to inform the patient correctly and completely and offer all available treatment, so the patient can make his or her own decision if interventions are considered in the disease management.

Inspired by the PhD work of Ilse Degreef, presented in 2009, the work and research on Dupuytren disease continued ever since. The PhD was titled ‘Therapy resisting Dupuytren disease: new perspectives in adjuvant treatment’. Epidemiological research was done to estimate the prevalence and identify patients at risk of progression to severe disability. This disability in Dupuytren disease and the influence of the extend of the disease was studied. basic research was focused on myofibroblast activation and its relation to recurrent contractures. The influence of surgical techniques on outcome and recurrence was evaluated and we concluded that recurrence was independent of the technique: ‘the surgeon can cut out the cords but not the disease itself’. Finally, innovative treatment options were introduced in therapy-resisting disease: the use of cellulose implants to isolate the skin and augment the firebreak effect of segmental fasciectomy appeared to improve outcome. The first Level 1 trial on neo-adjuvant pharmacotherapy demonstrated a role for possible disease control in the future.

Today, this work is continued. At the university, 2 PhD student, a clinical fellow, 3 residents and many medicine, physiotherapy and orthopaedic technician students work together in our team in a multi-disciplinary clinical and lab research project. We focus on translational research: putting bench into practice.

At Leuven University, today we focus on:

– The genetic background of Dupuytren disease in collaboration with the Laboratory of Complex Genetics

– The development of a lab animal model and research on the cellular function of the myofibroblast, in collaboration with both The research centre for Skeletal Biology & Engineering, and Molecular Digestive Oncology

– The influence of stem cells in collaboration  with the Peyronie Research Group

– Radiotherapy in therapy-resisting Dupuytren in collaboration with the Centre for Experimental Radiotherapy

– Clinical research on orthesiology, splinting and external fixation in collaboration with the Faculty of Kinesiology and Rehabilitation Sciences, IORT and the VIGO group

– Clinical outcome translational research on surgery and collagenase treatment in the Hand Unit at Leuven University Hospitals, Orthopedic Department.

DeGreef1Official inauguration of the Dupuytren Fonds at leuven University with Rector Rik Torfs (left) and Prof Dr Luc De Smet and Prof Dr Ilse Degreef (right)

DeGreef 2

(left to right) Prof Dr Luc De Smet, Prof Dr Ilse Degreef, Francois Mathys of the Belgian Patient Society and Rector Rik Torfs of Leuven University

United States

Dr Charles Eaton provided us with this summary of their goals and activities.

The Dupuytren Research Group is conducting research to develop a blood test for Dupuytren disease. A blood test is the missing piece of the puzzle needed to develop and test medical treatments for Dupuytren disease and related conditions. Right now, the ruler, protractor and camera are the only non surgical tools to measure a persons Dupuytren/Ledderhose disease. These only show what has already happened, not what is happening right now. A blood test could show what is happening right now, including the biologic response to medical treatment or to changes in diet, physical activity, or other lifestyle changes – before any changes in lumps or angles. A blood test could be used to test medical treatments for Dupuytren disease more quickly and accurately than has ever been possible.

The first goal of the  Dupuytren Research Group’s International Dupuytren Data Bank (IDDB) is to develop a Dupuytren blood test. This research is organised in three stages. Stage one is a large online survey of people with Dupuytren/Ledderhose disease – severity, how it impacts their life, and how other medical factors relate to their disease. Stage two is collecting blood samples from stage one participants and analysing these samples for genetic, immune, inflammation, dietary and other factors. Stage three is comparing blood test finding with the severity of Dupuytren disease. Stage one launched in 2015 and is growing daily. Stage two and three will be repeated in competitive cycles. Each cycle will select groups based on disease severity, collect their blood samples, and identify the best blood tests to repeat in the next cycle. Following cycles will do the same with more people and fewer tests until the best tests are confirmed. This strategy is designed to reduce overall costs. This strategy of repeated testing is also the fastest way to confirm the accuracy and reliability of a test available to all researchers to develop a cure for Dupuytren disease and related conditions. IDDB online enrolment is http://Dupstudy.com. Testing has started in 2020.

Pittsburgh University

In Pittsburgh, USA a team led by Dr Latha Satish MSc, PhD and Dr Sanjeep Kathju MD, PhD are working towards developing an animal model for studying the behaviour of Dupuytren’s tissue and understanding the differences between Dupuytren’s and non-Dupuytren’s cells, especially the expressions of genes and how the process could be influenced by medication.

Dr Satish kindly provided us with this explanation of the research:

Drs Latha Satish MSc, PhD and Dr Sandeep Kathju MD, PhD at the Department of Plastic Surgery, University of Pittsburgh, USA have been collaborating for many years now to understand the pathophysiology and the gene expression changes that contribute to the progression and/or recurrence of Dupuytren’s contracture. Our previous data examining the global gene expression patterns of DD-derived fibroblasts versus control carpal tunnel (CT)-derived fibroblasts confirms that there are numerous differences in their transcriptomes (mRNA expression) even in in vitro culture, indicating a stable intrinsically distinct disease pathology for DD-cells. Recently, for the first time, we have described an animal model for Dupuytren’s disease at the physiologically relevant orthotopic location. We also showed that gene expression differences seen between CT- and DD-derived fibroblasts persisted even in in-vivo. Using the animal model that we have developed which shows increased evidence of fibrosis in the forepaw that received the DD cells compared to CT cells we are currently pursuing with novel therapeutic interventions to diminish the DD-dependent fibrosis. We are also in the process of refining the animal model to recapitulate the disease completely. Our research is being funded by Private Donor Donation, Department of Plastic Surgery and the Pittsburgh Foundation.

In December 2018 the team registered a patent for the idea of using a transdermal cream with Pirfenidone (a drug used orally for patients with pulmonary fibrosis).  In tests on rats skin this penetrated through the skin into deeper areas, and the drug can change the extra cellular environment thus slowing or stopping fibrosis. Even if it is still far away from clinical use, the possibilities this invention raises are exciting.

(updated January 2019)