8th International Winter Conference on
AD DRUG THERAPY – HOPE AND REALITY
NEW TARGETS IN SIGHT?
We organised 10 years ago the first Winter Conference on new Drug Development in Alzheimer's disease in Zuers. At that time several promising compounds were in advanced clinical development already and we expected relatively soon new, in particular disease modifying treatments to be available for the AD-Patients. Unfortunately this hope has been disappointed because all of these new compounds failed in later stage clinical trials - this very often in spite of promising phase II clinical data.
But research in the field remained active and not only new therapeutic approaches have been developed but most importantly also new definitions of Alzheimer's disease. The big question still remains what is the right patient population to test new drugs, when shall we start treating, what are the right targets and finally what will be the best compounds? At the moment there is agreement that treatment should start as early as possible which results in the challenge of reliable early diagnoses. New developments in imaging technologies including in vivo determination of brain amyloid using PET and research on CSF as well as blood biomarkers should support early diagnosis. Still we have to be clear that so far no longitudinal validation of new diagnostic criteria is available, but first clinical trials using this patient population are on the way and results can certainly be expected in the not too distant future.
We will at our meeting also discuss new , sensitive neuropsychological tests, which should enable a better translation from preclinical findings to the clinical trial situation
At the moment majority of clinical trials are done in the field of immuno therapy, and it will be interesting to hear about the different developments in active and passive immunisation. This discussion can become extremely interesting because it is expected that before our meeting will be held in December first results from big phase III clinical trials should be available already.
Recent developments addressing modulation of ApoE is another promising approach to treat Alzheimer's disease, based on the fact that ApoE 4 is the major risk factor for developing the disease. Will promising preclinical data result in similar findings in clinical studies? Are there any other ways to counteract toxic amyloid beta species? Important research has been published about truncated pyro-glu Abeta about its role in initiation and propagation of the disease. The formation of this toxic species also opens new therapeutic targets. We follow this development in Zuers since the beginning – where do we stand now? Of course the interest in drug development also focuses on other targets like tau protein. Here a wide range of therapies has been developed and investigated, unfortunately not too many of the compounds were in clinical trials and so far no compound succeeded in late stage clinical development, but there are new ideas, also based on immuno therapy.
In addition there is again an increasing interest in small molecules interacting with neurotransmitter receptors acting on the cholinergic system but also on other receptors. The pharmacology of these receptors allows to conclude that such intervention will most likely not only provide symptomatic improvement but potentially also disease modification interacting with complex pathways regulating amyloid as well as tau metabolism. Some compounds are already in clinical development, others of them are close to enter early clinical phase, just another hope.
But there might be alternative ways to change our risk to develop Alzheimer's disease. One of the long-term interventions could be “healthy food” but of course also physical and mental activity. Recent clinical data raised hope. We will also look into this topic to explore the current status and ways into future development.
Most important for the small group that will meet in Zuers is certainly the high level of interaction and the perfect environment for open discussions and networking. Many new collaborations started here in Zuers. Therefore we are limiting the number of participants to a maximum of 90 people. I am sure that also this year we will have stimulating discussions.
The organisers are looking forward to welcoming you to the Austrian Alps beginning of December 2012!
For the organisers,
Ezio Giacobini, Abraham Fisher and Manfred Windisch