Neurosciences, a continuous journey of defeat and success

Neurosciences and the pharmaceutical industry have had a long-lasting, but not always happy relationship. Recently, Pfizer decided to abandon neuroscience research, a topic it had always been sensitive to. Yet failure is a step on the road to success.

A brief description of Neurosciences

Neurosciences is the combination of scientific studies on the development of the nervous system. These studies include knowledge in various areas such as math, physics, chemistry, statistics, cognitive science, computer science, psychology, linguistics, engineering and even philosophy. Neurosciences now involves more fields than ever before, using different approaches to study the cellular, evolutionary, functional, cognitive, computational and, naturally, medical aspects of the nervous system. Neuroscientists have also made great advancements in the development of artificial neural networks that have been applied to many different fields and not only to medicine and Biosystems.

Historical problems with pharmacology

Historically, neurosciences have had a complex relationship with pharmacological discoveries given how complicated the human brain is. “We haven’t had a new drug in years”, says Giovanni Biggio, Professor of Neuropsychopharmacology at the University of Cagliari, “mostly because we still do not know exactly how the brain functions. We have learned so much in the last twenty years, but recent drugs are always based on the same mechanisms”. Nonetheless, these difficulties have not hindered progress. Some recent success stories demonstrate this. Neurocrine Biosciences introduced a drug destined for patients affected by tardive dyskinesia, a debilitating pathology that provokes repetitive and involuntary movements and anomalies of the body. Sage Therapeutics, instead, reported several successful clinical trials with multiple compounds for serious forms of depression and postpartum depression.

Pfizer’s shocking announcement

In January 2018, Pfizer announced it would be ending its neuroscience development programs- not good news for the field of neurosciences. Could this be the first fallen domino in a chain reaction? Probably not. “Forget about Pfizer. There are at least 80 pharmaceutical companies working on neurodegenerative diseases and on Alzheimer’s”, Mario Melazzini, managing director of the Italian Medicines Agency (AIFA), affirmed on the Radio Anch’io program broadcast on Radio 1 Rai. Ultimately, despite the negative effects Pfizer’s abandonment will bring about, neurosciences continue to be an important field of research and experimentation and the great number of innovations created in the field of neurology make us optimistic for the future.

The Alzheimer enigma

Alzheimer’s is a disease that is deeply linked to neurosciences. Unfortunately, research for a cure to Alzheimer’s has been repeatedly unsuccessful. Many companies, however, have learned from the past and have optimized their programs, focusing on the specific protein that seems to be the problem, beta-amyloid (according to the most accredited hypothesis, the disease is provoked by an accumulation of the beta-amyloid protein that forms plaques in the brain, impairing the normal function of synapses), and treating patients at earlier stages of the disease. Research on beta-amyloid was carried out on mice at the Cleveland Clinic in America. Researchers observed the disappearance of amyloid plaques in the brains of mice affected by the disease and improved cognitive functions, demonstrating how the effects of certain drugs that block the BACE1 enzyme could eventually prove effective in humans. The researchers created mice that progressively lost the enzyme and noticed they remained healthy. Successively, these mice were bred with other mice that developed Alzheimer’s 75 days after birth. Results showed that the specially-bred mice developed Alzheimer’s as they aged even though enzyme levels were reduced by half. Yet as the mice continued aging and enzyme production diminished, the plaques disappeared altogether. In other words, reducing BACE1 enzymatic activity promotes the disappearance of plaques.

In addition to these positive results regarding the beta-amyloid protein, other strategies are emerging, such as those that target the Tau protein or those to combat neuro-inflammation.

More bravery and basic research

Gianluigi Forloni, director of the Department of Neurosciences at the Mario Negri Institute of Pharmacological Research in Milan, explains why drug development for central nervous system disorders is so problematic. ”An inadequate selection of patients, the complexity of the disease, the absence of strong clinical indicators, the difficulty of creating experimental models, the delays in transferring results to the clinic… We need to be more daring”, Forloni concludes, “more original, and not tread down the same beaten path. Of course, it won’t be easy. It’s not easy to convince the pharmaceutical industry to invest in innovative approaches that create more risk. Yet I believe that today, especially in the field of neurosciences, we need to make an effort to be more creative and develop better models and different approaches”.

For Giovanni Biggio, instead, the key issue is basic research. “We need to keep investing in basic research. This is why projects like the Human Connectome Project (which aims at mapping the neural pathways of the brain) and the Human Brain Project (which aims atsimulating the functions of the human brain through a supercomputer) financed by the U.S. National Institutes of Health (NIH) are extremely important in their contribution to decoding the human brain and developing new and revolutionary products”.

© Domedica s.r.l.

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