New drug shows neuroprotective and anti-inflammatory effects in murine models of Alzheimer’s

Alzheimer’s disease, the most common cause of dementia, is currently incurable. The current available medicines have very limited efficacy and only in mild stages of the disease. A team from the University of Barcelona has developed a promising therapeutic candidate to treat this disease that affects more than 800,000 people in Spain. According to a study published in the magazine ACS Pharmacology & Translational ScienceThe new drug has been shown to have neuroprotective and anti -inflammatory effects in two mouse models of the disease. The patent for the connection has a permit for a pharmaceutical company to start the pre -clinical and clinical examinations that are necessary for its approval.

This study is led by Mercè Pallàs, from the Faculty of Pharmacy and Food Sciences of the UB and the Institute of Neurosciences (Ubneuro) and Santiago Vázquez, from the same faculty and the UB Institute of Biomedicin (IBUB). The newspaper was also signed by UB researchers Christian Griñán Ferré, Julia Jarne Ferrer, Javier Sánchez and Sandra Codony. Experts from the Institute of Biomedical Research of Barcelona (IIBB) – A CSIC and the August Pi I Sunyer Biomedical Research Institute (Idibaps) Center – also participated in the Neurodegenerative diseases of the Center for Biomedical Research (Ciberned) and the University of Bonned).

A new approach to neuro inflammation

The study is the peak of seven years of research in which researchers have used a new approach, based on the inflammatory processes that contribute to activating the disease and modulating their progression. “Strategies that have been tried without success in the past ten years are specifically aimed at beta-amyloid accumulation and plaque formation in the brain, but there are indications that neuro inflammation is an important cause of Alzheimer’s disease. The approach of inflammatory processes has therefore become a promising therapeutic”

The new connection is an inhibitor of soluble epoxide -hydrolase (SEH), an enzyme involved in the regulation of various physiological processes, including inflammatory and pain response.

In the context of Alzheimer’s disease, inhibition of this enzyme can increase the levels of epoxyeicosatrienoic acids (Eet’s) bioactive molecules that reduce endogenous inflammatory drugs and thus promote neuro-inflammation and promote neuroprotection. “

Mercè Pallàs, researcher at Ciberned

The results of the study show that treatment with the new connection had neuroprotective effects in two mouse models of Alzheimer’s disease, culminating in an improved spatial and working memory and an improved neural network. “This can help to maintain neuronal function and reduce the neuronal death associated with Alzheimer’s disease,” says Santiago Vázquez.

These neuroprotective effects are due to the increase in eating acids, which are also involved in improving cerebral blood flow, which is crucial for maintaining the health of the brain. “Inhibition of SEH can therefore contribute to improved cerebral perfusion and protection against ischemic damage,” the researchers note.

Simultaneous effect on different anti -inflammatory paths

The advantage of this new drug compared to other anti-inflammatory connections that have failed in clinical studies and have not reached patients as a result of ineffectivity is that has been demonstrated that TSE-Auguste reduces the transcription and levels of multiple pro-inflammatory markers and at the same time improved ignitioning cytokines. “This global approach, which influences various inflammatory routes at the same time instead of just one, results in a neuroprotective effect that is sufficient to improve the symptomatology and pathology of Alzheimer’s disease,” the researchers emphasize.

In the study, the authors in fact show that the connection is effective compared to ibuprofen-a anti-inflammatory drug-where there is little importance in the animal model of the disease of family Alzheimer in which it has been tested. For the researchers this is a “very important” competitive advantage over other potential medicines.

Changing disease progression

The study also shows that treatment with the emergency room inhibitor is not only the progression of the disease, but is also able to change his course. According to the researchers, treatment maintains cognitive strengthening effects, even a month after the medicine has stopped in the mice. “What is even more important, the integrity of the neuronal network and the number of dendrite (a component of neurons) were kept, which suggests that the treatment is not only symptomatic, but the disease progression in the mouse model changes”.

Clinical translation challenges

Despite these encouraging results, the road to clinical application of this connection is still long and complex. The development of a new medicine includes a rigorous process with multiple phases: from first research and pre-clinical tests to clinical studies with patients and, finally, approval by health authorities. During this process, the drug must succeed for strict safety and efficacy regulations, a requirement that often requires decades of research and considerable financial investments.
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In that sense, the patent for the compound has given a license to an American pharmaceutical company to promote progress in the phase of pre -clinical and clinical tests. Members of the research team, led by professors Santiago Vázquez and Mercè Pallàs, follow the project within the company as expert consultants. “With this collaboration we can continue to participate, if the UB, in the development of the new connection to the treatment of pathologies with regard to neuro inflammation,” the researchers conclude.