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PL1: Putting research into practice

Detailed programme, abstracts and presentations

PL1: Putting research into practice

PL1.1 New medicines for Alzheimer’s disease: Lessons from past failures and perspectives for the future

WINBLAD Bengt

In 2010, the number of people affected by dementia worldwide was estimated to 36 million, with an estimated cost of approx 600 bUSD. The prevalence of dementia is expected to reach 115 million in 2050, with an equivalent cost increase. The progressive nature of dementia influences the whole life situation for families during several years-decades and so far, no cure or highly significant symptom relieving treatment is available. Increased understanding of the pathophysiology of Alzheimer disease (AD) has given us new therapeutic targets, and by using new biomarkers possibilities to diagnose patients earlier.

Many clinical and experimental studies are ongoing, mainly based on anti-amyloid-beta (Aβ) strategies, but the exact role played by Aβ in AD pathogenesis is not yet clear. We need to acknowledge that a single cure for AD is unlikely to be found and that the approach to drug development for this disorder needs to be reconsidered. Preclinical research is constantly providing us with new information of the complex AD puzzle, and an analysis of this information might reveal patterns of pharmacological interactions instead of single potential drug targets.

Since the last drug entered the market in 2002, many products in different development phases have failed. Why? Wrong molecules, inappropriate animal models, insufficient proof-of-concept studies, heterogeneous patient groups, too advanced disease, non-relevant outcome measures, intercenter variability in increasingly globalised multi-centre trials?

Our hope for the future is that new therapies could potentially slow or even halt the progression of the disease. Increased global collaboration between academia, industry and regulatory authorities is a vital step for a successful drug development.

We have good hope that until 2025, ongoing studies directed towards beta-amyloid and/or tau metabolism have proven effective and are on the market. Recently positive reports have been presented regarding passive immunotherapy and inhibition of beta-amyloid production.

PL1.2 Improving the timely diagnosis and providing adequate support to people with early memory complaints

PASQUIER Florence

Memory disorders are one of the most distressing symptoms with ageing. Alzheimer’s disease is famous and feared. However people are not all alike. Some worry quickly and want to know and understand what happens to them. Others reassure themselves, attribute their problem to inconvenience of age, or do not want to know, and temporize. Then will come the time when memory problems are so severe than the persons will forget that they forget and deny their troubles up to refuse assistance and support. This is not easy for the entourage. Many studies show the advantages of an early diagnosis for the patient: relief to understand what is going on, proper care, and appropriate attitude of the close relatives, increased empowerment…  And now, innovative therapies are tested in people at risk for developing Alzheimer’s disease because of the presence of lesions associated with this disease in their brain, before any symptoms. Surveys have shown that most people say they want to know if they will develop Alzheimer’s disease, but much less will follow the process when the opportunity arises. A too early diagnosis may communicate uncertainty. On the other hand, a timely diagnosis refers to the subjective experience of the disease, and meets the concerns of the patients and their close relatives. Recommendations guide the diagnosis disclosure process, and help breaking bad news. The diagnostic process, like the disclosure itself, has a time frame. It is useful to know what are the patients’ knowledge and thoughts regarding both their current symptoms and their possible causes. It allows to correct erroneous beliefs and to personalize the disclosure. The process should not be too long, nonetheless its duration permits the patients to progress in their relation with the disease and diminish the brutality of the disclosure situation.

PL1.3 From biomarkers to clinical trials – big data and public-private consortia for Alzheimer’s disease prevention

LOVESTONE Simon

Despite increasing knowledge and understanding of the mechanisms of Alzheimer’s disease and related dementias generated in academia, and the considerable efforts of the pharmaceutical industry to develop therapies, we are all only too conscious of the repeated failure of drug trials at late stage. This is enormously costly to the companies who for the most part fund such trials, to the health services and even economies of all of our countries but most of all to those with dementia today and who will suffer from dementia tomorrow in the absence of a therapy for disease modification. It is not clear why the trials are failing. Is it because we have only an incomplete understanding of the condition? Is it that the trials are conducted too late in the disease process? Or is it simply that the drugs don’t work well enough? Clearly no one truly knows the answer to this but what is overwhelmingly clear is that this is a very hard problem and hard problems tend to require new solutions. It isn’t enough to continue to do the same thing.

One potential, and partial, solution to the hard problem of Alzheimer’s disease is the innovative use of data and another is public private partnerships. Neither are truly novel but arguably neither have been used to quite the same degree as is being implemented by two Innovative Medicine Initiatives (IMI) – the European Medical Information Framework (EMIF) and the European Prevention of Alzheimer’s Disease studies (EPAD). These large, pre-competitive public private consortia bring together university and other public and third sector organizations together with many large pharma and small biotech and other companies. EMIF is focused on the re-utilisation and aggregation of data and cohorts for dementia research including especially the identification of novel biomarkers for early, preclinical and prodromal detection. EPAD is establishing a registry, a trials ready cohort and an innovative clinical trial that is dependent on the use of such biomarkers. Together with the Alzheimer’s Research UK Drug Discovery Alliance and the Dementias Platform UK and other national initiatives, the research community in Europe has established a tremendously exciting platform that looks set to make a contribution to the generation of novel therapeutics for early, preclinical disease modification; in effect leading the search to establish a preventative therapy for Alzheimer’s.

PL1.4 Prevention of Alzheimer’s disease – Myths, wishes and reality

PIRTOŠEK Zvezdan

Because Alzheimer’s disease (AD) is such a devastating disease, many unproven and unscientific prevention strategies are advised and patients may be tempted by untried, unproven, and unscientific treatments.
Risk factors can be divided into two groups: those that can not be controlled and those which can be influenced by certain health, lifestyle and environmental factors.

1. Risk factors for AD that are beyond our control include age and genetics. The risk of developing the disease doubles every 5 years over age 65 and it is estimated that up to half the people older than 85 have AD. Genetic link to two frorms of AD has been found: (i) early onset AD (before the age of 65) is associated with changes in certain genes on three chromosomes; (ii) risk of late onset AD (after the age of 65 y) is increased with the APOE ε4 form of the APOE gene, while the APOE ε2 form of this gene may provide some protection.

2. However, a number of health, lifestyle, and environmental factors may help lowering the chances of developing AD: (i) factors modifying cardio-vascular risks (e.g. controlling levels of cholesterol with diet or drugs – statins, controlling levels of homocystein by increasing intake of folic acids and vitamins B6 and B12); (ii) lowering high blood pressure levels; (iii) controlling diabetes and insulin resistance (treatment with rosiglitazone); (iv) mechanisms of inflammation and antiinflammatory drugs; (v) antioxidant mechanisms (vitamins E, C, selenium); (vi) estrogen-related mechanisms;  (vii) immunization as a possible preventive strategy; (viii) exercising regularly; (ix) engaging in social and intellectually stimulating activities.
For the time being, it is not possible, unfortunately, to prevent or even delay AD. However, ongoing studies (overviewed in the talk) clearly suggest that certain life styles, activities and substances might reduce the effect of possible AD risk factors.

 

 
 

Last Updated: Thursday 24 September 2015

 

 
  • Acknowledgements

    The 25th AE Conference in Ljubljana received funding under an operating grant from the European Union’s Health Programme (2014-2020). Alzheimer Europe and Spominčica gratefully acknowledge the support of all conference sponsors.
  • European Union
  • Roche
  • SCA Global Hygiene
 
 

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