SCOTTISH HOSPITAL NEWS ENCOURAGING NEWS ON ANTIBIOTIC CHALLENGE
Scientists working to develop a ‘game-changing’ new antibiotic have made a signifi cant advance towards creating commercially viable drug treatments by producing two simplifi ed synthetic versions of the substance which are just as potent at killing superbugs like MRSA as its natural form.
The breakthrough by researchers at the University of Lincoln marks another important step to realising the potential of teixobactin in aiding the global fi ght against antibiotic- resistant pathogens. Teixobactin is a recently discovered natural antibiotic which many in the international scientifi c community believe could lead to creation of the fi rst commercially viable new antibiotic drug in 30 years.
The Lincoln team has successfully synthesized new simplifi ed versions of teixobactin which harness the same powerful antibiotic effects in a way that could be produced on a commercial scale. Their fi ndings are published in the Royal Society of Chemistry’s journal, Chemical Science.
Until now, scientists attempting to synthesise teixobactin believed they
needed to use cationic (or positively charged) amino acids which bind to the bacterial target using a ‘side chain’. This meant they had to use either the very rare amino acid found naturally in teixobactin, called enduracididine, or alternative ones which had lower potency against superbugs.
Each amino acid sits at a specifi c place in teixobactin’s structure, and the Lincoln team has now successfully replaced enduracididine – which holds position ten – with two alternative amino acids which are not positively charged. These amino acids lack the ‘binding’ part, over-turning the prior understanding that enduracididine is essential for to so-called ‘target binding’ to be highly potent against superbugs.
With this new knowledge, synthesised versions of teixobactin can be more easily developed, taking the process from up to 30 hours to just ten minutes for a single coupling step – a signifi cant step towards turning teixobactin into a viable new drug. Importantly, the two new simplifi ed forms of teixobactin have also proven to have identical potency against superbugs as the natural form of teixobactin.
SMC PLACES RESTRICTION ON CLADRIBINE
The Scottish Medicines Consortium (SMC) has issued fi nal advice recommending restricted use of cladribine tablets (MAVENCLAD®) as an option for treating adults with highly active relapsing multiple sclerosis (MS) as defi ned by clinical or imaging features.
The SMC restriction applies to:
• Patients with rapidly evolving severe relapsing-remitting MS: patients with two or more relapses in the prior year whether on treatment or not, and at least one T1 gadolinium-enhancing lesion.
• Patients with sub-optimal therapy
relapsing-remitting MS: patients with one or more relapses in the previous year while on disease modifying therapy, and at least one T1 gadolinium-enhancing lesion or nine T2 lesions.
The advice marks a step change in the treatment options available for patients in Scotland with highly active relapsing-remitting MS as cladribine tablets are the fi rst short-course oral therapy, with a maximum of 20 days’ tablets taken in the fi rst two years of treatment, without the need for frequent monitoring.
RESEARCH NEWS
LIVER STUDY INSIGHTS INTO HARD-TO-TREAT DISEASES
Researchers from the University of Edinburgh have identifi ed a key cell process that could cause damage to bile ducts and help explain some liver diseases.
The team’s experiments showed that triggering the process harms vital cells in bile ducts, while blocking the process reverses liver damage in mice. The fi ndings could help develop new treatments for bile duct diseases, which are linked to increased risk of cancers and liver failure, researchers say.
The university team was seeking to better understand how disease is caused in bile ducts - small channels that run through the liver that help the body dispose of waste - and examined liver tissue donated by patients with chronic bile duct disease.
As a result, they found evidence of a cell process known as senescence, which was not seen in healthy people. Senescence – when aged cells no longer undergo natural division – has an important role in the normal function of the body. However, the research shows that senescence also contributes to disease, preventing repair of damaged bile ducts caused by wear and tear, leading to liver failure.
NEW POTENTIAL DRUG TARGET FOR DEADLY PARASITIC DISEASE FOUND
It’s commonly known as the cat parasite and has found itself in the headlines after medication prices recently skyrocketed in America. Now researchers at the University of Glasgow have found a potential new weakness in the toxoplasmosis-causing parasite, potentially paving the way for new drug development for the disease.
In new a study, published in PLOS Pathogens, scientists at the University of Glasgow’s Wellcome Centre for Molecular Parasitology have identifi ed a key enzyme in the Toxoplasma parasite that is crucial for its survival, and may also be a potential new drug target.
In 2015 one of the main drug treatments for the disease, Daraprim, hit the headlines in America after Turing Pharmaceuticals raised the price from $13.50 a tablet to $750 a tablet. Treatments for toxoplasmosis often have toxic side effects, while there are no current drugs available to clear out the dormant form of the parasite.
Now, University of Glasgow researchers have highlighted the importance of thioredoxins – enzymes uniquely essential for the Toxoplasma parasite’s survival. They are currently working with industry partners to create new drugs which would effectively target this enzyme and kill the parasite.
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