Innovative Medicines Initiative: Tracking progress in Alzheimer’s research
11.12.13
This Wednesday the UK is hosting the first ever G8 summit devoted to the topic of dementia. This initiative is timely: Dementia and dementia-related illnesses are an increasing concern for many societies facing ageing populations. The healthcare industry has long been aware of this growing threat, and many relevant research initiatives have been established to target this issue.
A recent study publication identifying the role of specific “biomarkers” in learning more about preclinical Alzheimer’s disease shows great promise for future diagnoses – and potential treatment. But what is a biomarker anyway? And how will this actually impact patients? EFPIA’s Director of Science Policy, Magda Chlebus, examines the progress achieved with support from the Innovative Medicines Initiative’s European Medical Information Framework (EMIF) project – and attempts to clear away the scientific jargon and explain the impact of study results on real-world patients – in a way they will understand.
Background
Alzheimer’s Disease, or AD, doesn’t suddenly appear out of nowhere. It has a preclinical phase; a period where the disease is developing in the body, but cognitive ability is normal – symptoms are yet to be seen. The discovery of biomarkers [1] has opened the door to earlier identification. Basically the study wanted to further test the significance of 3 preclinical categorisations of AD, which are defined by their biomarkers [2] . The question at hand: Can these biomarkers reliably determine not only the onset of AD, but also the progression of the disease? With a better understanding of such biomarkers, we can improve diagnosis of Alzheimer’s – and come closer to a cure.
Study Process and Outcomes
The study aimed to use biomarkers present in study participants’ cerebrospinal fluid – aka CSF markers – to define 3 different stages of preclinical AD. Long-term cognitive and mortality outcomes were measured in each participant in each of the pre-clinical AD stages. From 1998 to 2011, study participants underwent annual mental assessments.
So how were changes in study participants measured? Participants were ranked using the Clinical Dementia Rating (CDR): A numeric scale used to determine the severity of dementia symptoms. The CDR measures symptoms on a scale of 0 to 3 (none to severe) and measures impairment in six areas –everything from memory to orientation and personal care. A CDR of minimum 0.5 indicates mild impairment or dementia – this number is key to the study’s conclusions, so keep it in mind.
What this Means for Patients
The results of the study are complex – but they allow researchers to conclude that preclinical AD can be defined by CSF markers. Consider this: 31% of participants had preclinical AD (stages 1-3); those with markers indicating preclinical AD progressed faster to a CDR of minimum 0.5 – in the CDR scale. Remember, a ranking of at least 0.5 indicates very mild impairment or dementia (the CDR scale goes from 0, no dementia, to 3, severe dementia).
So, what’s this mean? The study indicates a strong link between “preclinical AD” and future cognitive decline. This means researchers can be more confident in targeting treatments aimed at preclinical AD. Keep in mind, the study we are talking about here was based on three definitions of “preclinical AD”, all of which have biological indicators (see the box below). Knowing that these biological indicators have significance gives researchers more confidence in using them to define preclinical AD – and they can thus further research that addresses these biological factors, and moves towards a cure.
The results of the study discussed here are a step towards patient stratification [3] and the development of targeted therapies [4]. Targeted therapies have already shown success in treatments developed for certain types of cancer, and there is great hope that they can be further applied in other areas – including AD. If we can similarly define AD using essential biomarkers, and develop targeted treatments based on this information, we will improve the odds of finding effective treatments for AD. And that means a step towards targeted treatments that could, one day, do real world patients suffering from AD real good.
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[1] Biomarker: A biological “sign” that can be used to help identify a disease. In the case of AD, determined biomarkers are neurochemical indicators, which can show a potential risk or presence of AD.
[2] Three preclinical stages of AD as, determined by biomarkers:
- Cognitively normal individuals with abnormal amyloid markers: Amyloid markers, in this case an “Amyloid Beta” marker (AB), is a peptide – a short chain of amino acids. AB peptides are the main ingredient in amyloid plaques — the buildup of amyloid proteins – which have been found to form in the brains of AD patients.
- Cognitively normal individuals with both abnormal amyloid and neuronal injury markers: In this stage, the individual has both abnormal amyloid markers present, as well as neuronal injury markers: Neurons are the essential signal-senders of the brain, and a mark of neuron injury may indicate a problem that impedes with normal brain function.
- Individuals displaying subtle cognitive changes, with both abnormal amyloid and neuronal injury markers.
[3] Patient stratification: the process of screening and sorting potential participants ahead of a clinical trial to see if they are a good fit for the possible treatment in question. For AD, this could entail sorting participants into varying stages of pre-clinical AD. More effective patient stratification is thought to be an important factor in more efficient and effective development of modern medicines – notably targeted therapies.
[4] Targeted therapies: Treatments are determined based on the molecular makeup of a disease, as well as the patient’s genes. In the past, medicine had a symptomatic approach to diagnosis and treatment – patients were diagnosed and prescribed medicines based on the symptoms they showed. For something like AD, this is a very ineffective approach – because the symptoms of cognitive decline associated with AD are also associated with other types of dementia. By determining the biological factors underlying the disease, researchers can develop medicines based on the disease.
