You often read headlines in the press like “Trial Failed” or “Another Alzheimer’s Drug Sinks.” But if you delve deeper, the reality I see as a scientist in this field is different. There is progress happening.
It is slower than what patients would need and what we would like. But I do see forward momentum in our growing scientific understanding of the disease, both in terms of its complexity but also in terms of how to tailor therapies to patients.
Also, from a number of trials, we are seeing a consistent signal of clinical efficacy that, albeit weak, appears to be reproducible. I’m talking about independent sets of observations all pointing in the same direction, namely that amyloid removal and cognitive stabilisation or preservation correlate with each other.
We know that Aß deposits in the brain are not the only driver of cognitive decline. The peptide tau, as well as neuroinflammatory changes, represent other key features of Alzheimer’s disease, also known as AD. What I find really exciting is that we may be able to start combining drugs as we learn what each may contribute in isolation.
AD is such a hugely complex illness with so many degenerative activities going on in the brain in parallel that it is highly unlikely that a single drug with a single mechanism of action will be all that patients need. The ultimate aim is indeed a cure. However, approaches that we are currently studying are unlikely to provide a cure in the sense of returning patients to their pre-disease level of cognition. Rather, they are more likely to lead to cognitive stabilisation and the prevention of further decline.
Ideal would be to intervene early in the disease process, when there is still a lot to save. It is hard, but not impossible, to identify patients in the pre-clinical or pre-symptomatic setting. I like to compare AD to an iceberg, where most of the disease activity happens slowly below the surface, before you see the first symptoms. It is only after decades of things taking place silently in the background that the symptoms start to peak above the surface.
What we call AD is probably a spectrum of different overlapping illnesses, characterised by a menu of pathophysiological processes going on in the brain. As we accumulate the tools and better biomarkers, we will be able to tailor a particular combination of therapies that best fit individual patients.
It will probably be similar to the situation in oncology where you take a tumour sample and look for its mutation status, and then you select a portfolio of drugs that will target the different underlying drivers of disease. I think we are on the right path.