23 June 2005

Findings Published in June 23 Issue of New England Journal of Medicine.

June 23, 2005 ?Brussels? The JDRF- Center for Beta Cell Therapy in Diabetes and the Juvenile Diabetes Research Foundation (JDRF), the world's leading charitable funder of research into type 1 diabetes, announced today that short-term treatment with an anti-CD3 antibody (ChAglyCD3) can preserve residual beta cell function in recently diagnosed type 1 diabetes patients, and thus prevent further loss of insulin production for at least 18 months. This finding, reported in the June 23 issue of the New England Journal of Medicine, represents an important step in the search to prevent and stop type 1 diabetes by altering the clinical course of the disease.

This Phase II clinical trial was undertaken by a team of clinicians and researchers from Belgium, France, Germany, United Kingdom (listed at end). It was led by Dr Lucienne Chatenoud (Hôpital Necker, Paris) with Dr Bart Keymeulen (Academic Hospital, Vrije Universiteit Brussel) as clinical coordinator. The trial is one of the projects undertaken by the JDRF Center for Beta Cell Therapy in Diabetes, directed by Dr Daniel Pipeleers (Vrije Universiteit Brussel).

The study was conducted on eighty patients with type 1 diabetes enrolled in Belgium and in Munich (Germany). Patients who received a six-day course of antibody treatment immediately after diagnosis, maintained, over the 18 month follow-up period, a higher insulin production, ie residual beta cell function, than patients who received a placebo. They were found to need lower doses of injected insulin to maintain blood glucose control. This benefit was primarily seen in patients who presented with a less pronounced loss in insulin production at diagnosis. Side effects were minor and short-lived including flu and mononucleosis-like symptoms.

"These exciting results provide enormous hope that we can preserve residual beta cell function by modulating the autoimmune attack and, in fact, change the clinical course of type 1 diabetes," said JDRF Executive Vice President for Research Dr Insel "There is no other current treatment that can actually change the clinical course once the disease has begun. This study shows we are on the right track, and opens the door for researchers to target this treatment specifically to individuals who would receive the most benefit."

This clinical trial extends an earlier JDRF-supported study published in 2002 by Drs Herold (New York) and Bluestone (San Francisco) using a similar antibody. The present work was conducted as a placebo-controlled study in a much larger group of patients and measured residual insulin production, ie beta cell function, at start and following treatment. This allowed the researchers to track and compare ChAglyCD3's effect in patient subgroups who at diagnosis presented a lower or a higher loss in residual beta cell function. The team observed that the antibody's protective effect was much more pronounced in patients who had undergone a lower loss before receiving the drug. This is not only useful for defining the patient population to be treated but also underlines the importance of diagnosing the disease at an early stage when the loss in residual beta cell mass has not yet fully developed. Interventions that can preserve endogenous insulin production are expected to result in better metabolic control of diabetes, and thus delay or reduce diabetes-related complications such as eye, nerve and kidney disease.

As stated by Dr. Chatenoud, "A tremendous amount of work was put into this study, and I am thrilled with the outcome. The team of clinicians who dedicated themselves to this effort are to be commended for their work. These included, in Belgium, Dr Bart Keymeulen (Academic Hospital Vrije Universiteit Brussel), Dr. Chantal Mathieu (UZ Gasthuisberg, Katholieke Universiteit Leuven) and the Belgian Diabetes Registry, and in Germany Dr. Anette Ziegler (Schwabing Hospital, Munich). And I would be remiss for not mentioning that the international collaboration within the JDRF Center allowed this trial to proceed in an efficient manner."

"Our trials benefit from the unique collaboration within our JDRF Center: scientists in diabetology, immunology, clinical biology and beta cell biology are working together as a team with the same objectives. JDRF made this possible." said Dr Pipeleers. "We can now inform patients that this team work has made a step towards stopping the disease but will also have to explain why more work is needed before a therapy will be available for clinical practice."

About Anti-CD3

Anti-CD3 antibodies such as the presently used ChAglyCD3 are engineered to block the function of CD3 cells, ie immune T cells that orchestrate the destruction of beta cells. The antibodies prevent "activation" of this family of white blood cells after they have identified their target, disarming them once they are poised to attack. ChAglyCD3 is a humanized, non-mitogenic anti-CD-3 antibody, a new type of agent showing promise for this kind of intervention. It was conceived and manufactured by Drs. Herman Waldmann and Geoff Hale (Oxford, United Kingdom).

About the JDRF Center for Beta Cell Therapy in Diabetes

The JDRF Center for Beta Cell Therapy in Diabetes is an international consortium of clinical and research departments. Its objective is to develop and implement strategies for prevention and treatment of diabetes. Basic and clinical research projects aim to preserve and restore insulin producing beta cells in diabetes. In addition to the presently described Antibody Intervention Trial, the Center conducts a Beta Cell Transplant Trial in type 1 diabetic patients. The Coordination Core of the Center is located on the medical campus of Vrije Universiteit Brussel (Belgium).

Contact New York

  • Eileen Brangan
  • National Manager, Media Relations
  • Juvenile Diabetes Research Foundation
  • 1-212-479-7577
  •  ebrangan@jdrf.org

Contact Brussels

About JDRF

JDRF (www.jdrf.org) was founded in 1970 by the parents of children with juvenile diabetes -- a disease that strikes children suddenly, makes them insulin dependent for life, and carries the constant threat of devastating complications. Since inception, JDRF has provided more than $800 million to diabetes research worldwide. More than 80 percent of JDRF' expenditures directly support research and education about research. JDRF's mission is constant: to find a cure for diabetes and its complications through the support of research.

The following institutions and individuals contributed to this study:

Belgium contact

Academic Hospital and Diabetes Research Center-Vrije Universiteit Brussel
Bart Keymeulen, Evy Vandemeulebroucke, Leonard Kaufman, Frans Gorus, Pieter De Pauw, Denis Pierard, Ilse Weets, Daniel Pipeleers

UZ Gasthuisberg, Katholieke Universiteit Leuven
Chantal Mathieu

University Hospital Universitaire Instelling Antwerpen
Christophe De Block

Hôpital Erasme, Université Libre de Bruxelles
Michel Goldman, Liliane Schandene, Laurent Crenier

Belgian Diabetes Registry
Network of over 200 diabetologists, pediatricians and researchers from all universities and over 100 non-university hospitals in Belgium

Germany contact

Hospital München-Schwabing, Munich
Anette G. Ziegler, Markus Walter

United Kingdom contact

Sir William Dunn School of Pathology, Oxford
Geoff Hale, Peppy Rebello , Pru Bird , Eleanor Berrie, Mark Frewin, Herman Waldmann

France contact

INSERM U580-IRNEM, Hôpital Necker, Paris
Sophie Candon, Jean-François Bach, Lucienne Chatenoud

CHU Michallon, Grenoble
Jean-Marie Seigneurin