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Why we still don’t have a cure for Alzheimer’s

Why we still don’t have a cure for Alzheimer’s Why we still don’t have a cure for Alzheimer’s

Photographer:Fotograaf: archive Wim Riedel

Pharmaceutical drug developers need multidisciplinarily trained researchers

After oncology, most research money goes to neurodegenerative diseases such as Alzheimer's or Parkinson's. Among people over 80 years of age, dementia prevalence exceeds 20%. Paradoxically though, our knowledge of the brain has increased more than ever in the past decades, yet this is not yielding more new medicines. This is one of the challenges faced by students of the unique new UM research master specialization Drug Development and Neurohealth.

It made headlines recently: “Pharma giant Pfizer quits research and development of new medicines for Alzheimer’s and Parkinson’s disease”.

And what’s worse, says Wim Riedel, professor of experimental psychopharmacology: they closed down their entire neuroscience drug research department. “Pfizer didn’t really top the ranks in this area, but still had to let go 150 researchers. Other pharma companies, such as GlaxoSmithKline, threw in the towel years ago”.

The reason? Shareholders have become more impatient, says Riedel, who worked for 10 years in Pharma R&D, five years with GSK in Cambridge (UK) and five years with Roche in Basel. “For decades, pharma companies have been investing billions in development of new medicines, but they did not come up with more approved new medicines. The strange thing is, while we know more and more about the brain and the central nervous system, we neuroscientists do not seem able to produce more approved new medicines.”

There are various causes for this, of which some are simply practical. “Research has become much more expensive, because of stricter regulatory requirements. For example, while clinical trials  on patients in the recent past lasted only three months, nowadays this often takes at least years”.

More importantly, scientific hypotheses keep changing. “For years it was thought that clearing abnormal protein deposits in the brain would cure Alzheimer’s, but the support for this research line is decreasing. Pharma companies then started thinking that we should start treatments in an earlier prodromal stage of the disease, but even this appears to be too late. Currently the focus is on studying the effect of vaccinating healthy, middle-aged people (40-50 yrs) lacking any disease symptoms but having a familial genetic vulnerability for early Alzheimer’s Disease”.

School of thought

A cure for Alzheimer’s, but also for depression (more efficacious than current antidepressants and with fewer side-effects), has become a kind of holy grail, Riedel agrees.

Two years ago, in collaboration with the departments of Toxicogenomics and Pharmacology and Personalised Medicine, he started the specialisation Drug Development and Neurohealth, as part of the 2-year research master Cognitive and Clinical Neuroscience. “The strength is in its multidisciplinary character. We teach the students – who already have a biomedical or a psychology bachelor’s degree – a variety of research methods, from wet lab research, big-data analyses and neuroimaging techniques to behavioural research and its methodology. In industry there is a high demand for academics with such a broad profile. They work in project teams consisting of researchers with completely different backgrounds. From my own experience, I know that molecular biologists, medicinal chemists, and behavioural scientists can speak completely different languages. Team members do not think the same way and do not necessarily understand each other’s scientific contribution to their shared project. The new specialisation is unique students come from all over Europe, but also from countries as far away as the USA, Canada and Brasil.”

115 years old

After oncology, most research funding goes to neurodegenerative diseases. “And in terms of medical need, I think neuropsychiatric drugs are on top of the list. The number of patients with Alzheimer’s disease is expected to triple in the next 30 years. This is because of a twofold population aging: as people live longer the prevalence of neurodegenerative diseases is on the rise, and at the same time the birth rate is going down.”

Of course, Alzheimer’s and Parkinson’s disease were around before the last three decades. Alzheimer’s is named after the doctor who first described the condition in 1905, says Riedel. “However, these diseases were less in the spotlight, because people had a shorter life span. But now, when you are over 80, the risk exceeds 20 percent.”

Does this mean the brain has an expiration date? “Yes, it looks like it, although there are exceptions. Hendrikje van Andel lived to 115 and was still very bright. Genes can be read out too. Carriers of the Apo-E4 gene have an increased Alzheimer’s risk. Carriers of Apo-E2 on the other hand have a decreased risk. There are companies these days who can map your whole genome if you provide them with a bit of your saliva and a couple of hundred euros.

A team member at Roche, a Psychiatrist who also conducted Alzheimer studies, had this done. Bad news, he turned out to be E4 carrier. I would only want to know this myself when there is a registered cure available.”

Public-private

Riedel looks back at his time working in the(?) pharma industry with pleasure. “It is a far larger scientific community than the university, there is more money for research. Also, it is a very interesting place to broaden your horizon, to discover how substances can work. The downside of the(?) industry is its bottom-up mindset. In other words: biology determines behavior. After all, they manufacture drugs that affect people. But the reverse is also true: behavior and thoughts affect biology. For example, just consider placebo-effects. The top-down mindset is one of the benefits of being trained as a psychologist.”

Another downside is that the scientific programmes of these company departments are influenced and driven by shareholders and profit. “Pharma companies will always emphasize that their primary existence is to help healing the ill. Yet some have turned their backs on complete neuroscience programs. Currently in Europe public-private consortia are emerging, in which industry and academia form disease-oriented research partnerships. That is a fascinating trend.”

In September the first UM student cohort will graduate. They will spread out to laboratories in companies and academia, but Riedel is confident they will land  in the right spots. The fourteen students in the first cohort had no trouble finding interesting positions for their internships; they are presently working at pharma companies Roche (Basel) and Grünenthal (Aachen), a biotech company Antidote Therapeutics (USA) and at university departments of Harvard (USA), Ottawa (Canada), Fukuoka (Japan), Cork (Ireland) and Maastricht.

 

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