This is the second story in an S&P Global Market Intelligence series focusing on Alzheimer's disease. The healthcare news team will examine promising therapies and the failures that have riddled the drug pipeline along the way.
➤ The U.K. Dementia Research Institute, or DRI, a national network of 50 laboratories, has seen "quite a lot" of interest from industry players seeking collaboration.
➤ Future treatment for Alzheimer's disease is likely to offer tailored combination of therapies coupled with early diagnosis.
➤ The Dementia Discovery Fund, a venture capital fund backed by Bill Gates, is looking at a couple of projects from DRI labs. "For sure there will be increasing interaction on projects between the U.K. DRI and the DDRF."
Giovanna Lalli, head of scientific affairs at the U.K. Dementia Research Institute at University College London, spoke to S&P Global Market Intelligence about the Alzheimer's market. Following the failure of recent high-profile late-stage research projects — notably Biogen Inc. and Eisai Co. Ltd.'s aducanumab and Roche Holding AG's crenezumab — researchers are exploring new approaches to the degenerative disease that move beyond the so-called amyloid, also known as abeta, and tau hypotheses. Understanding of the development of this disease is still in its infancy and much basic research is ongoing, according to Lalli.
Giovanna Lalli, head of scientific affairs at the U.K. Dementia Research Institute at University College London.
S&P Global Market Intelligence: What is the current state of play in Alzheimer's disease research?
Giovanna Lalli: Many people have focused on the amyloid hypothesis and getting rid of these plaques that are formed of toxic abeta fragment and there's a whole range of studies still going on, especially using antibodies, so trying to either stimulate the immune system to produce antibodies to destroy these plaques or just ready-made antibodies that you can inject into patients that can target the formation, the accumulation of these plaques. So hope is not completely gone.
Do we need to go back to the drawing board with basic research?
Dementia is a very complex world and we still do not understand much about the basic mechanism so it's not only toxic accumulation of abeta amyloid. Clearly, basic findings are coming out from different labs around the world that point to a very complex mix of mechanisms, a whole range of systems that are failing and we still need to really understand the causes of this. A lot of effort is ongoing, Bill Gates is putting more money into biomarkers and early diagnosis and digital technologies to try to really detect the first signs, very very early — we're talking about decades before the cognitive decline, the memory impairment, starts to show.
Interim results suggested that Biogen's aducanumab was not heading in the right direction some time ago. Is the trial data still important?
Absolutely. A very important thing to stress is the willingness of companies to share the data. A lot can be learned. This can help avoid mistakes in the future, design better trials, learn a lot about the potential of target effect. It's absolutely key to share negative data, failure data. I think Bill Gates is making a lot of effort [on this] with platforms for data sharing, which is absolutely precious. So every trial — we say it's a failure — but it's actually another step in increasing our knowledge.
What findings have emerged from going back to the basic research?
It's important that we really try and reinvigorate this target pipeline and that's where the basic research is key because if you start to look into identifying new signaling pathways, new pathways in the cells that are disrupted in this disease in different models using animals, but using also patient-derived stem cells for example — which now can be done, we have new technologies that are really opening new pathways for research for better understanding what are the dysfunctions in these cells. If we can differentiate them into a whole load of different cell types — neurons, microglia which really seem to be key players in the pathogenesis of Alzheimer's disease — we can study them in the dish, then we can go to animal models. We can also learn more from the biomarker studies as well because the biomarkers in humans can give us clues to bring this information back to the test model in vitro.
What about the role of diagnostics and biomarkers in early diagnosis?
Early diagnosis is going to be a key thing in better trial design, in identifying the right populations and in intervening at the right time. We are also very much involved in biomarkers. There are new technologies today that enable the detection of these molecules at very, very low levels. In very small samples, for example from cerebral spinal fluid, you can test extremely low amounts of these molecules. Technological advances have opened up new ways to study neuro-degeneration.
Are we "moving past amyloid" or will a combination approach yield more success?
It's clear that abeta amyloid is a feature and of course tau also. It may be something that has to do also with impacting the immune system signaling ... because genetic studies in populations clearly point to microglia [cells that act as immune defense cells in the central nervous system] as some key players in the pathology of Alzheimer's disease. There is a specific receptor in microglia that is [generating] a lot of interest. That's clearly a very big risk factor for AD. So by trying to modulate this receptor maybe and trying to at the same time, act on tau and abeta, that could be maybe something more effective in slowing down the progress or maybe can be even preventative at some point, if someone can identify populations at risk. In fact we have people looking at ways to calculate the risk of getting AD based on the genotype. One of our investigators can actually predict with 85% probability whether you are going to be at risk of getting the disease.