A drug developed against cancer is reborn as a therapy for neurodegenerative diseases

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By CAPosts 16 January, 2021 - 05:30pm 67 views

It is not the first time that a drug developed for a disease ends up being useful, due to an unexpected side effect, for other diseases. The best known case is that of sildenafil, a compound developed in the United Kingdom to treat high blood pressure and angina pectoris and which ended up being a popular drug against erectile dysfunction. Also methylphenidate was originally designed to treat depression in adults and ended up as a therapy for inattentive hyperactivity syndrome. Now, it has been the department of Molecular Biology and Biochemical Engineering of the Pablo de Olavide University (Seville) that has patented the STX64, a drug initially thought for cancer, as a treatment for pathologies or effects of aging, such as Alzheimer's, Parkinson's or Huntington's disease. "We have proven that it delays, improves and could reverse neurodegenerative diseases", highlights Manuel Jesús Muñoz, one of the authors of the research, published in Nature Communications .

Muñoz's team at the Andalusian Center for Developmental Biology (mixed center of the CSIC, Pablo de Olavide and the Junta de Andalucía) investigates steroid hormones, which regulate multiple biological processes, such as reproductive function, and are related to aging. Naturally, these hormones progressively lose their balance in sulfate concentration. Two proteins are involved in this process, the sulfatases, which eliminate the chemical component, and the sulfotransferases, which add it. This imbalance is behind the effects of age and the neurodegenerative diseases associated with them.

The initial objective was to develop a gene therapy that would allow, as occurs in young organisms, to enhance the proteins that increase the concentration of sulfates and inhibit the that eliminate it, according to Muñoz. But, at the same time, a multinational pharmaceutical company that has asked not to be identified was conducting research on the compound STX64 as an inhibitor of steroid sulphatase, the protein that reduces the concentration of sulfates. In this case, the goal was the treatment of hormonal endometrial and breast cancers.

Investigations of the drug reached the first phase of clinical trial, in which it was found that the toxicity was tolerable. However, the results against tumors did not improve those obtained with other existing drugs, so its development was abandoned.

However, Muñoz's team discovered that the effect achieved by the compound, which can be administered orally, was the same as the one they were looking for with gene therapy, so they began to investigate its use in diseases associated with aging.

The work began on specimens of Caenorhabditis elegans, nematodes of one millimeter in length that have served as a model for biology since the seventies and those who induced Alzheimer's. The results showed that STX64 reduced sulfatase activity, improved disease symptoms, and increased longevity in healthy specimens. The same results were reproduced in experiments carried out with mice, which also reflected improvements in memory capacity.

Research has continued and it has been shown that the drug, in addition to inhibiting the protein that reduces the concentration of sulfates, also decreases plaques of protein aggregates in the brain, another of the symptoms of Alzheimer's and other neurodegenerative diseases.

The finding has led researchers to register the use of STX64 "for the treatment of the effects of aging and, therefore, to increase the longevity of individuals or improve their quality of life ", according to the text of the European patent .

A company has also been developed, Olavide Neuron STX SL (ONSTX) , with the participation of the Sevillian university, to complete the development and marketing of the compound. There are already investors who have contacted the group of researchers, according to Muñoz, who hopes to be able to complete the second phase of clinical trials in one year.

The multinational that developed, in collaboration with the University of Bath and the Imperial College, the first phases of the trial with the drug have yielded the initial studies, so the usual process can be shortened. The results of the tests showed that 36% of the women treated with the compound did not show disease progression within six months of treatment, but the response and survival data were similar to those obtained with existing drugs.

However, the new application discovered by Spanish researchers can turn this drug into a new weapon if the objective is modified: the effects of aging and the neurodegenerative diseases associated with it.

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Source: Elpais

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