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First Human Trial of Senolytics Is Successful

14 January 2019
Giulio Prisco

Senescent Cells

Senolytic drugs that target senescent cells, also covered in the previous issue of Pulse, continue to make news, with the publication of the first data on the successful treatment of an age-related disease (see below). UT Health San Antonio researcher Dr. Anoop Nambiar discussed the human trial for safety of a combination of two senolytic drugs - drugs that target senescent cells - in an interview with Texas Public Radio.

"(Senescent cells) basically are these zombie-like cells that are dysfunctional - they don't work properly - but at the same time, they don't die,” explained Nambiar. “They create a toxic environment so other cells and other tissues don't work properly."

“We picked IPF [idiopathic pulmonary fibrosis] as a prototypical disease associated with aging,” Nambiar said. “But also because it’s such a devastating disease, and so there’s really a significant unmet need for better treatments and more effective, safer treatments for IPF patients.”

“Cellular senescence is clearly emerging as a main player in aging,” said UT Health San Antonio researcher Dr. Nicolas Musi. “Previously, no published data existed to demonstrate that drugs targeting cellular senescence could be safely given to older patients, or that they might be used to treat diseases of aging such as IPF.”

First trial of senolytic drugs in humans shows encouraging results. Researchers at UT Health San Antonio, Mayo Clinic, and Wake Forest School of Medicine, have released the first data on the treatment of an age-related disease with drugs called senolytics. According to the scientists, the results in patients with deadly idiopathic pulmonary fibrosis, described in a study published in EBioMedicine, are encouraging and indicate the feasibility of larger clinical trials.

New bioinspired nanoscale drug delivery method. Researchers at Washington State University and Pacific Northwest National Laboratory have developed a novel way to deliver drugs and therapies into cells at the nanoscale without causing toxic effects that have stymied other such efforts. According to the scientists, the work, described in a study published in Small, could someday lead to more effective therapies and diagnostics for cancer and other illnesses.

ON switch for CRISPR gene editing. Scientists at UC Berkeley have created an 'on' switch for CRISPR-Cas9, described in a research paper published in Cell, which allows it to be turned on in select cells only, specifically those that have a particular protein-cutting enzyme, or protease. Viruses produce such proteases, as do cancer cells, so the Cas9 variants - called ProCas9 - could be used as sensors for viral infections or cancer.

New designer protein has anticancer effects. Scientists at UW Medicine's Institute for Protein Design have created a new protein that mimics a key immune regulatory protein, interleukin 2 (IL-2). IL-2 is a potent anticancer drug, but with toxic side effects. In a study published in Nature, summarized and analyzed in a Nature News & Views commentary, the researchers report using computer programs to design a protein that they have shown in animal models to have the same ability to stimulate cancer-fighting T-cells as IL-2, but without triggering harmful side effects.

3D-printable drug sponge reduces the side effects of chemotherapy drugs. Scientists at UC Berkeley have developed a drug sponge that could minimize the side effects of cancer treatment. Catheters are used today to deliver drugs directly to tumors to avoid broadcasting toxic chemotherapy agents throughout the body. Nevertheless, half of the drug can escape to the rest of the body, causing side effects. Doctors treating liver cancer teamed up with chemical engineers to design a 3D-printable polymer-coated device, described in a research paper published in ACS Central Science, which can be temporarily placed in the vein coming out of the liver to absorb unused drugs, potentially lowering risk.

Cancer death rate declining. A steady, 25-year decline has resulted in a 27% drop in the overall cancer death rate in the United States, translating to approximately 2.6 million fewer cancer deaths between 1991 and 2016, according to data provided by the American Cancer Society. The data come from Cancer Statistics, 2019, the American Cancer Society's widely-quoted annual report on cancer rates and trends. A scientific article is published in CA: A Cancer Journal for Clinicians, and is accompanied by a consumer version, Cancer Facts & Figures 2019.

Protein could drive new bone building. Johns Hopkins Medicine researchers have suggested that a cellular protein signal that drives both bone and fat formation in selected stem cells can be manipulated to favor bone building. The scientists’ experiments with rats and human cells are described in a study published in Scientific Reports. If harnessed in humans, the scientists say, the protein - known as WISP-1 - could help fractures heal faster, speed surgical recovery, and possibly prevent bone loss due to aging, injury, and disorders.

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