Gene Silencing: A New Frontier In Medicine?

Could inherited diseases now be treated by a newly-developed treatment called “gene silencing"?

By: Ringo Bones

Gene silencing had shown really promising results after a recent trial treatment to treat an inherited disease called porphyria – a crippling illness often linked to the madness of King George III. Patients with prophyria participating in the trial treatment of a new drug saw attacks of crippling pain reduced by 90-percent on average with half of them had resulted in the elimination of chronic pain. Porphyria is an inherited disorder which means people with the disorder cannot produce haem – a vital component of hemoglobin in red blood cells that transport oxygen around the body – and therefore suffer a painful buildup of chemicals called porphyrins. In the 1960s, psychiatrists suggested that the inherited illness might explain the mania suffered by King George III, based on evidence that he had purple urine which is a main symptom of the disorder.

The newfangled treatment uses an approach called gene silencing. A gene is part of our DNA that contains the blueprint for making proteins, such as hormones, enzymes or raw cellular building materials. But our DNA is locked away inside a cell’s nucleus and kept apart from a cell’s protein-making factories. So our bodies use a short strand of genetic code, called messenger RNA, to bridge the gap and carry the instructions. This drug, called givosiran, kills the messenger in the process known as RNA interference. In acute intermittent porphyria, the drug lowers the levels of an enzyme involved in haem production and prevents the buildup of toxic proteins.

Prof. David Rees from King’s College London treated patients taking part in the trial in the UK. He told the BBC that “this is a really important treatment   - it’s innovative. Porphyria is one of the first conditions it has been used successfully. I’m genuinely surprised how well it works in this condition and I think it offers a lot of hope in the future.” Gene silencing has been used to treat a genetic disease that causes nerve damage and the US Food and Drug Administration said such medicines “have the potential to transform medicine”. Other ongoing trials have shown that the gene silencing drug givosiran has the potential to treat other inherited diseases but it is still in its very early days. A similar approach is also being investigated in Huntington’s disease, which is caused by a buildup of a toxic protein that kills brain cells. Researchers are also looking into it as an alternative to statins for lowering cholesterol.

Climate of Secrecy Surrounds a Drug Resistant Fungus?

After a patient died after 90 days being admitted in Mount Sinai Hospital, why is there a so-called climate of secrecy surrounding Candida auris – a deadly drug-resistant fungus?

By: Ringo Bones

An elderly man died from the fungus last year at Mount Sinai Hospital following abdominal surgery and yet the Trump Administration had never issued a public health warning. A drug-resistant superbug fungus variant of Candida auris has sickened nearly 600 people across the United States in recent years, including more than 300 patients in New York State, the Centers for Disease Control and Prevention had reported. Candida auris, a fungus that normally preys on people with weakened immune systems can be deadly if not treated properly. “Most Candida auris cases in the United States have been detected in the New York City area, New Jersey and the Chicago area,” the CDC said in a statement. The fungus was seen in the United States for the first time in 2013, Dr. Lynn Sosa, Connecticut’s deputy state epidemiologist had told The New York Times that she views Candida auris as “pretty much unbeatable and difficult to identify.” But why is it that the so-called “veil of secrecy” surrounding Candida auris has just been recently lifted and at most without the attendant press fanfare?

According to the CDC, symptoms of the fungus may be difficult to detect because patients are often already sick and only a lab test can identify the superbug. Candida auris can cause different types of infections, including bloodstream infection, wound infection and ear infection. People that recently had surgery, live in nursing homes, or who have breathing tubes, feeding tubes or central venous catheters appear to be at highest risk. “Based on information from a limited number of patients, 30 to 60-percent of people with C. auris infections have died. However, many of these people had other serious illnesses that also increased their risk of death,” the CDC said.

While most Candida auris infections are treatable with antifungal medications, the CDC says its concerned that some variants of the fungus have proven to be resistant to all three main classes of antifungal medications. “In this situation, multiple antifungal medications at high doses may be needed to treat the infection.” The CDC said.

3D Organ On A Chip: The Future Of Drug Research?

Primarily developed to increase the accuracy of drug research in the lab, could a 3D Organ On A Chip also point to the future of cruelty-free drug testing by reducing the use of lab animals?

By: Ringo Bones

The newfangled device, which incorporates cells inside a 3D transistor made from a soft sponge-like material inspired by how cells in nature are structured, now allows scientists the ability to study cells and tissues in new ways. By enabling cells to grow in three dimensions, the device more accurately mimics the way that cells grow in the body. The researchers, led by the University of Cambridge say their device could be modified to generate multiple types of organs – a liver on a chip or a heart on a chip, for example – ultimately leading to a body on a chip which would simulate how various treatments affect the body as a whole. Their results are reported in the journal Science Advances.

Traditionally, biological studies were – and still are – done in petri dishes, where specific types of cells are grown on a flat surface. While many of the medical advances made since the 1950s, including the polio vaccine, have originated in petri dishes, these two-dimensional environments do not accurately represent the native three-dimensional environments of human cells and can, in fact, leas to misleading information and failures of drugs in clinical trials. “Two-dimensional cell models have served the scientific community well, but we now need to move to three-dimensional cell models in order to develop the next generation of therapies,” says Dr. Roisin Owens from Cambridge’s Department of Chemical Engineering and Biotechnology and the study’s senior author.

Cambridge University’s 3D Organ On A Chip could also spell good news on the reduction of the use of lab animals which could eventually lead to cruelty-free drug testing. Remember how Canadian scientists Fredrick G. Banting and his team discovered insulin back in 1921? They extensively used dogs in their lab to find out how insulin works and how it could be used to treat Type-1 diabetes in humans and unfortunately, it resulted in the deaths of many dogs.

Could Drugs That Target Zombie Cells Make Us Live Forever?

Although it is still on early trials yet on mice, could drugs that target “zombie cells” be used to make us live forever?

By: Ringo Bones

Mayo Clinic in the United States are conducting early trials on senolytics: anti aging drugs that can slow and even reverse the ageing process, in a bid to ward off diseases like Alzheimer’s, cancer, heart disease and diabetes that showed really promising results on lab animals. A senolytic is among the class of small molecules under basic research to determine if they can selectively induce death of senescent cells – also known as zombie cells. The goal of those working to develop senolytic agents is to delay, prevent, alleviate, or reverse age-related diseases. Multiple possible senolytic agents are under investigation. Certain anti-cancer agents may, in low doses, decelerate aging and age-related diseases. Targeting cancer prevention with anti-cancer agents may confer longevity effects by offering protection from metabolic pathologies during aging, independently of effects of cancer. Navitoclax, also known as ABT-263, was originally studied as an anti-cancer drug.

Cellular senescence – i.e. how zombie cells behave inside our bodies – is one of the causes of aging because the inflammatory signals generated by growing numbers of senescent cells or zombie cells disrupt tissue maintenance and cell function and play an important role in many age-related conditions, including osteoarthritis. The best approach in dealing the senescent cells inside our bodies appear to be a simple one – destroy them. These so-called zombie cells accumulate slowly and therapies that selectively remove senescent cells have been shown in animal studies to produce significant reversal of numerous aspects of aging.

Research on flushing out those so-called zombie cells from our bodies to reverse the human aging process is still on its early stages. Most biochemical startups are focusing on some anti-cancer drugs. Others are researching the stem-cell route to make zombie cells revert into less harmful normal cells. But research into the use of existing of-the-shelf anti-cancer drugs that target zombie cells is the one that currently shows the most promise. Even the relatively inexpensive and widely available diabetes drug metformin has been studied for its anti-aging effects for a number of years because this drug was found out to inhibit the nasty secretions of senescent cells.