The Warsaw Voice » The Polish Science Voice » Monthly - August 28, 2015
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A Breakthrough in Treating Dementia?
A team of Polish scientists, doctors and pharmacists is working on a drug that could provide a new way to treat Alzheimer’s disease. The drug does not offer a cure, but is expected to significantly improve memory.

Alzheimer’s disease and related dementias, which affect some 44 million people worldwide according to recent estimates, involve the loss of synapses—contact points via which nerve cells relay signals to one another—and a parallel deterioration in brain function, notably in the ability to remember. A protein fragment called beta-amyloid has been widely considered responsible for destroying synapses.

Unlike most other available treatments, the new drug will not focus on beta-amyloid, but instead on one of the receptors of serotonin, the so-called happiness hormone.

The dementia drug is expected to improve memory and cognitive processes—the set of mental abilities and processes related to the acquisition of knowledge. It may also have antidepressant and anxiolytic (anti-anxiety) effects.

The drug is being developed as part of the research project “New non-amyloid treatment of cognitive disorders” (NATCo) by a scientific and industrial consortium made up of the Jagiellonian University Medical College in Cracow, the Polish Academy of Sciences’ Institute of Pharmacology in Cracow, and Celon Pharma, a pharmaceutical company based in Kiełpin near Warsaw.

During the last two decades, scientists have focused on beta-amyloid as the sole cause of Alzheimer’s, but none of the research has proven it, according to Maciej Wieczorek, Ph.D., CEO of Celon Pharma, which will be responsible for going commercial with the drug.

“We have focused on serotonin receptors of type 6 (5-HT6),” says Wieczorek. “We have more and more data that these receptors may have a beneficial effect on cognitive processes, or the creation and modification of knowledge. It is these processes that are impaired in various types of dementias.”

Wieczorek cautions that the drug is unlikely to lead to a cure. “In this concept, we may have no influence on the cause of the disease, but we can significantly improve the condition of patients,” he says.

5-HT6 receptors are located mainly in the central nervous system. They are one of 14 receptors of serotonin, the hormone of happiness. Regulating their activity may be particularly important for patients suffering from dementia and psychological problems.

The agreement on establishing the research consortium was signed in February. The project is managed by a team made up of Paweł Zajdel, Ph.D., from the Jagiellonian University Medical College, Prof. Andrzej Bojarski from the Institute of Physics, and Wieczorek with Mikołaj Matłoka from Celon Pharma. The Jagiellonian University’s Center for Innovation, Technology Transfer and University Development helped determine the principles of the consortium’s operations.

Once the drug is developed, the consortium partners will look for a health center to conduct clinical trials. The project includes the development of biologically active chemical compounds. Modern synthesis methods make it possible to produce a large number of compounds in small quantities within a short time. Some of these compounds will undergo biological, pharmacological, behavioral, preclinical, quality and analytical tests, in addition to tests on animals.”

The Jagiellonian University and the Polish Academy of Sciences’ Institute of Pharmacology are responsible for designing the compounds, their synthesis, and biological and pharmacological research,” says Wieczorek. The project joins science and industry and “the partners divided their roles according to their expertise.”

The project includes not only finding the right substance, but also tracking how its concentration in the patient’s body changes over time, how the substance is metabolized, and an assessment of how safe it is to use. First, the researchers want to check the impact of selected compounds on animals, including evaluation of the neuropsychological and cognitive functions of rats. On the basis of how the animals behave, the researchers will draw conclusions on whether the animals are depressed, whether their perception is distorted in any way, and whether the animals are agitated.

“We are checking, for example, how long a rat swims in the pool, how long it takes to locate a target and how many times it smells its partner during the day, or how long it focuses its attention on a specific object,” says Wieczorek. “With such detailed studies we can pretty much tell about the effect of a potential drug.”

Danish, American and British scientists are also conducting research on the 5-HT6 receptor. In the case of neuropsychiatric drugs, researchers have to overcome many limitations. The first concerns studies of animal behavior, which, for all their complexity, do not provide the full picture. In the case of substances that affect the brain, improving memory and enhancing cognitive abilities, all information is indirect. Another important limitation is the blood-brain barrier, which impedes the entry of a potential drug to the patient’s nervous system, Wieczorek says.

Pharmacological, safety and toxicological studies are a critical step in the development of a drug. These studies seek to confirm that an active substance does not cause adverse effects in the body. Especially in neuropsychiatry, it must have the proper chemical properties and an ability to maintain certain concentrations, absorption and penetration into the nervous system. It should stay in the body for a specific time and be controllably removed. Only substances that meet all these conditions are candidates for ultimate use in therapy.

The Celon-Pharma company produces drugs for patients with schizophrenia, hypertension, diseases of the central nervous system, and breast cancer, as well as drugs used in treating the Human Immunodeficiency Virus (HIV). The company’s labs develop both generic and innovative drugs used in the treatment of cancer and neuropsychiatric, metabolic and inflammatory conditions.

The NATCo project is scheduled to run until 2017. Its total budget is zl.4.8 million, including zl.4.1 million in co-financing from the National Center for Research and Development under its Applied Research Program, which seeks to strengthen collaboration between research institutions and companies interested in applying research results in business practice. Celon Pharma will pick up the rest of the tab.
Karolina Olszewska