Senolytics for the treatment of lungs
Medicines for old age have been tested for the first time in humans
Researchers at UT Health in San Antonio, collaborating with the Mayo Clinic and Wake Forest University School of Medicine, were the first to publish the results of treating a deadly disease in humans with drugs called senolytics. The results were published by the journal EBioMedicine (Justice et al., Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study).
Senolytics are the very anti–aging drugs (English senolytics from senile – senile and lytic – destructive) – they are able to specifically initiate the death of aged cells. The fact is that the process of cleansing the body of old cells slows down with age, damaged cells persist and become toxic to surrounding tissues. This contributes to the development of multiple age-related diseases, including idiopathic pulmonary fibrosis (ILF), which leads to scarring in the lungs.
ILF is a devastating and progressive lung disease with an average survival rate of less than five years after diagnosis. Usually the disease affects adults over 60 years of age. In fact, the only treatment option is lung transplantation, but it is not always available.
In the first experimental study, 14 elderly people with a diagnosis of ILF from mild to moderate severity participated. Each participant received two senolytic drugs, dasatinib and quercetin. The drugs were taken orally for three consecutive days of the week, and this was repeated for three consecutive weeks (nine doses in total).
The research team measured biochemical markers before and after the administration of senolytics, and conducted weekly thorough surveys on quality of life and side effects to obtain preliminary evidence of safety and tolerability. The team also evaluated markers of physical function, including the distance of a six-minute walk, walking speed, the number of repetitions of getting up and sitting on a chair, the index of bone fragility based on clinical analyses, and biological analyses of proteins secreted by toxic cells and associated with aging.
The most consistent improvements after senolytic therapy were observed in the mobility of participants. A six-minute walking test, sit-up repetitions and other indicators were significantly improved after the treatment was completed. Most patients showed an increase in mobility of more than 5%. Other markers of physical function, including lung function, have not changed.
Until now, no drug therapy, including available antifibrotic drugs, has ever given similar results in patients with ILF, especially with regard to increasing the distance traveled in 6 minutes. In this experimental study, this walking distance increased by an average of 21.5 meters.
The most common side effects reported by patients after therapy were respiratory symptoms such as cough and shortness of breath, gastrointestinal discomfort or heartburn.
At the moment, dasatinib and quercetin are approved by the FDA. They are effective in eliminating aging cells of different types. The same combination of drugs in animal models improved the course of Alzheimer's disease.
However, it is too early to draw far-reaching conclusions about the effectiveness of drugs. Firstly, the pilot study was small (14 patients), and secondly, the study did not include a control group of patients with ILF who would have taken a placebo rather than a senolytic. However, the success of the mini-experiment makes it possible to attract more participants to obtain more convincing results.
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