Check GAD antibody positivity with the Diamyd anti-GAD RIA plate*

forewordResearch Scientists throughout the world are currently facedwith a time-old challenge – to define and understand themechanisms leading to development of autoimmune diseases,and then to determine and develop efficient means oftreating or preventing them. While these might sound like two distinctchallenges, the definition of the molecules targeted in an autoimmune diseaseprocess also provides the candidates for therapeutic targeting.To date, there is no vaccine for any of the many autoimmune diseases thataffect millions of people throughout the world. A number of candidate moleculeshave been identified and targeted, such as insulin in Type 1 diabetesand myelin basic protein in Multiple Sclerosis, but clinical vaccination trialsusing these molecules have not yet been successful. Given the recent advancesin gene technology and knowledge of the genetic codes comprising bothMan and experimental animals, the potential for discovery of new candidatemolecules is great. However, one candidate molecule identified manyyears ago still stands the test of time.Glutamic acid decarboxylase 65 (GAD65) is a candidate autoantigenimplicated in development of the autoimmune disease Type 1 diabetes. Inautumn 1994, ‘The Story of GAD’ by Robert Dinsmoor appeared in theCountdown magazine, a publication of the Juvenile Diabetes ResearchFoundation International. This article described the series of research discoveriesencompassing the period 1982-1993 that led to definition ofGAD65 as a prime candidate autoantigen in Type 1 diabetes. The articleended with two pertinent statements – that access to recombinant GADin industrial-sized quantities would be required for testing of GAD therapiesin humans, and that GAD-based therapies should provide a meansof preventing diabetes.During the last 10 years, intensive efforts have led to development ofhigh quality recombinant GAD65 proteins, which have been tested inPhase I and Phase II clinical trials.Additionally, recent research efforts havealso identified GAD as an important elementin Parkinson’s and other neurologicaldiseases, indicating that the candidate moleculehas not only remained a potential keyto prevention of diabetes, but also importantin treatment of other diseases as well. Thereis obviously still more to learn about thisfascinating protein.This issue is dedicated to GAD65 with anumber of contributions made by several prominent GAD researchers. Aswell as personal reflections of their own past experiences of GAD, thecurrent status and proposals for future applications of GAD are presented.We hope you find these articles interesting.Assoc. Prof. Robert A. HarrisintroductionIntroduction byLars KlareskogIn 1999 diamyd medical initiated a unique cooperationwith the Karolinska Hospital whensetting up its Competence Center forAutoimmune Diabetes (DMCCAD) at theCenter for Molecular Medicine (CMM) atKarolinska. Since its inception, with Robert Harris atthe helm, DMCCAD has become an interesting pointfor cross-fertilization of ideas related to various autoimmunediseases including Type 1 diabetes, MS andRheumatoid Arthritis.It is generally agreed that Glutamic AcidDecarboxylase 65 (GAD) is an important antigen inType 1 diabetes. As in other autoimmune diseases,recent research is focused on induction of tolerance todisease specific antigens. This may protect self structuresunder attack without interfering with the immunesystem’s capabilities in other areas, such as combattingviral infections or cancer.While it is already generally accepted that GADantibodies (GADA) is a major diagnostic marker forType 1 diabetes and predicting the course of developmentof Type 2 diabetes (LADA-patients), toleranceinduction to GAD may become a way to prevent thedevelopment of insulin dependency in LADA patients.I have had the pleasure of being able to follow thedevelopment of Diamyd Medical’s GAD-based vaccinefor LADA patients. The outcome of the Phase IIstudy in LADA patients is important, not only becauseit may lead to a new drug for diabetes therapy, butits results may also be of importance when designingfuture clinical trials in other diseases such as MS.page 4 dmccad june 2003