Long-acting drug effectively prevents HIV-like infection in monkeys

Cabotegravir (USAN  and INN ) (also known as S/GSK1265744 or previously referred to by the research code GSK744) is an investigational new drug under development for the treatment of HIV infection. It is an integrase inhibitor, with a carbamoyl pyridone structure similar to dolutegravir. In investigational studies, the agent has been packaged intonanoparticles (GSK744LAP) conferring an exceptionally long half-life of 21–50 days following a single dose. In theory, this would make possible suppression of HIV with dosing as infrequently as once every three months.

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HIV researchers hope a new compound, known as cabotegravir, could make dosing easier for some because the drug would be administered by injection once every three months. A clinical trial testing long-acting cabotegravir's safety and acceptability has already begun at multiple U.S. sites including The Rockefeller University Hospital. Meanwhile two new studies, including one conducted by researchers at the Aaron Diamond AIDS Research Center (ADARC) and Rockefeller University, published today (January 15) inScience Translational Medicine, show that long-acting cabotegravir injections are highly protective in a monkey model of vaginal transmission of a virus similar to HIV.

"Clinical trial results have demonstrated that the effectiveness of preventive oral medications can range with results as high as 75 percent effective to as low as ineffective, and a lot of that variability appears to hinge on the patient's ability to take the pills as prescribed," says study researcher Martin
Markowitz, a professor at Rockefeller University and ADARC. "Long acting cabotegravir has the potential to create an option that could improve adherence by making it possible to receive the drug by injection once every three months."

Developed by ViiV Healthcare and GlaxoSmithKline, and previously known as GSK744 LA, cabotegravir is an antiretroviral drug. Antiretrovirals interfere with HIV's ability to replicate itself using a host cell and they are used to treat an HIV infection or to prevent those at high risk from acquiring it in the first place.

Long-acting drug effectively prevents HIV-like infection in monkeys 

In continuation of my update on Century-old drug reverses autism-like symptoms in fragile X mouse model.

In continuation of my update on Suramin

Researchers previously reported that a drug used for almost a century to treat trypanosomiasis, or sleeping sickness, reversed environmental autism-like symptoms in mice. Now, a new study suggests that a genetic form of autism-like symptoms in mice are also corrected with the drug, even when treatment was started in young adult mice.

Century-old drug reverses autism-like symptoms in fragile X mouse model  

Venom of cone snails provides leads for possible treatment of cancer...

There are approximately 500 known species in the genus Conus, and each have their own distinct venom.  These toxins are aptly named conotoxins.  Conotoxins are small, structured peptide toxins.  This means they are bonded by peptide bonds, which are bonds between the carboxylic end of one amino acid to the amine end of another.  These peptides work by targeting and blocking ion channels of either the voltage-gated or ligand-gated class.  These ion channels are where action potentials in neurons are created.  Therefore, if no ions can get through to the neuron, no action potentials can be made and sent to other neurons, and the prey organism is paralyzed.  It is most likely that differentConus members target different specific ion channels, depending on the animals they feed on.

While considered a delicacy in some parts of the world, snails have found a more intriguing use to scientists and the medical profession offering a plethora of research possibilities. Cone snails are marine mollusks, just as conch, octopi and squid, but they capture their prey using venom. The venom of these marine critters provides leads for detection and possible treatment of some cancers and addictions. Frank Marí, Ph.D., professor in the Department of Chemistry and Biochemistry in FAU's Charles E. Schmidt College of Science at Florida Atlantic University, has focused his research on cone snail venom and has published a study in the current issue of the Journal of Biological Chemistry.

"The venom produced by these animals immobilizes prey, which can be worms, other snails and fish," said Marí. "The venom is an extraordinary complex mixture of compounds with medicinal properties."

Venom of cone snails provides leads for possible treatment of cancer, addiction

PF-114 shows promise in therapy-resistant CML, Ph-positive ALL

PF-114, a selective tyrosine kinase inhibitor (TKI), is active against native and mutated forms of the BCR–ABL oncogene in Philadelphia chromosome (Ph)-positive leukaemias, according to preclinical cellular and in vivo results published in Leukemia.

Martin Ruthardt, from Goethe University in Frankfurt, Germany, and colleagues found that PF-114 was more selective than the second-generation TKIs dasatinib and nilotinib as well as the third-generation TKI ponatinib, which they speculate could reduce the potential for adverse effects.

At a 100 nM concentration, equivalent to an active plasma concentration, PF-114 inhibited at least 90% activity of 11 kinases compared with 47 and 36 kinases suppressed by ponatinib and dasatinib, respectively. Nilotinib blocked only four kinases at this concentration, but extrapolating the data to its clinically relevant concentration of 4 µM resulted in the number of inhibited kinases increasing to 21.

In cell-free assays, PF-114 inhibited not only native ABL kinase but also versions of the enzyme harbouring various clinically relevant mutations, including T315I. The agent also suppressed the proliferation of Ph-positive cell lines derived from patients with chronic myeloid leukaemia (CML) or acute lymphatic leukaemia (ALL).

Additionally, PF-114 was effective against patient-derived long-term cultures, including those responsive and resistant to TKIs as well as one with nonmutational TKI-resistance.

Treatment with PF-114 significantly increased the median survival of mice transplanted with cells expressing the native or T315I mutant form of p185BCR–ABL, inducing a CML-like disease, compared with untreated mice, from 28 days to 39 days and 68 to 132 days, respectively.

Ref : http://www.nature.com/leu/journal/vaop/ncurrent/full/leu2014326a.html

PF-114 shows promise in therapy-resistant CML, Ph-positive ALL

U-M researchers identify how amlexanox drug improves metabolism of sugar

Amlexanox (trade name Aphthasol) is an anti-inflammatory antiallergic immunomodulator used to treat recurrent aphthous ulcers (canker sores), and (in Japan) several inflammatory conditions. This drug has been discontinued in the U.S

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Researchers at the University of Michigan have identified how a promising drug in clinical trials for the treatment of obesity and related metabolic disorders improves the metabolism of sugar by generating a new signal between fat cells and the liver.

In addition to illuminating how the drug, amlexanox, reverses obesity, diabetes and fatty liver disease, the findings suggest a new pathway for future treatments. The research was published Jan.12 in Nature Communications.

Investigators in the lab of Alan Saltiel, the Mary Sue Coleman Director of U-M's Life Sciences Institute, had previously discovered that this drug, which had been used in the treatment of asthma, also has the ability to cause weight loss and improve diabetes in obese mice.

The current study revealed that amlexanox exerts its effects through a specialized type of fat cell by increasing the level of a second messenger molecule called cAMP. In turn, cAMP increases the rate by which cells "burn" fat so that the animal loses weight. But amlexanox also triggers the release of the hormone interleukin-6 from these fat cells, which then travels in the circulation to the liver. In the livers of diabetic mice, interleukin-6 reduces production of glucose, so that overall blood sugar is lowered.

"We know that amlexanox works to reverse obesity and insulin resistance in part by resolving chronic inflammation and increasing energy expenditure, but that's not the whole story of the drug's effects," said Shannon Reilly, first author of the study. "Understanding how the drug also enables crosstalk between fat cells and the liver in obese mice allows us to see more of the amlexanox picture--and also sheds light on communication between different tissues in the body."

U-M researchers identify how amlexanox drug improves metabolism of sugar

Review shows that fish compound can help combat cardiovascular disease

Urotensin-II (U-II) is a peptide ligand, initially isolated from the neurosecretory system of the Goby fish (Gillichthys mirabilis). For many years it was thought that U-II does not exhibit significant effects in mammalian systems; a view quickly overturned when it was demonstrated that Goby U-II produces slow relaxation of mouse anococcygeus muscle, in addition to contraction of rat artery segments. In 1998, the cDNA encoding a U-II precursor was cloned in humans, unequivocally demonstrating its existence in mammalian species.The vasoconstriction it induces can cause or exacerbate hypertension, congestive heart failure, and coronary artery disease.

In fish, U-II is secreted at the back part of the spinal cord, in a neurosecretory center called uroneurapophysa, and is involved in the regulation of the renal and cardiovascular systems. In mammals, it is involved in the regulation of the cardiovascular system.

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A major international review of a peptide originally found in fish that could be used in the battle against cardiovascular disease has been published.

Professor David Lambert from the University of Leicester's Department of Cardiovascular Sciences contributed to the review, which has been largely written by the International Union of Basic and Clinical Pharmacology (IUPHAR) subcommittee, to pull together the vast literature on Urotensin II (UII), a peptide first isolated from teleost fish.

UII activates a G protein-coupled receptor called UT to modulate a number of signalling pathways including intracellular Calcium. Interestingly, the peptide can constrict some blood vessels yet dilate others.

The review, which is published in the high impact journal Pharmacological Reviews, has shown that UII can modulate a vast array of biologic activities encompassing the cardiovascular system, kidneys and central nervous system.

Professor Lambert said: "We have been working on this exciting peptide for a number of years; it exhibits a very interesting pharmacological profile. Design and evaluation of small molecule drugs has potential for use in the treatment of several cardiovascular diseases."

Review shows that fish compound can help combat cardiovascular disease

Aptose begins APTO-253 clinical study in patients with relapsed or refractory hematologic malignancies

Description of APTO-253 (LOR-253): APTO-253, also known as LOR-253, LT-253,  is a small molecule inhibitor of human metal-regulatory transcription factor 1 (MTF-1) with potential antitumor activity. MTF-1 inhibitor LOR-253 inhibits MTF-1 activity and thereby induces the expression of MTF-1 dependent tumor suppressor factor Kruppel like factor 4 (KLF4). This subsequently leads to the downregulation of cyclin D1, blocking cell cycle progression and proliferation. This agent also causes decreased expression of genes involved in tumor hypoxia and angiogenesis

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Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, today announced dosing of the first patient in its Phase 1b clinical study of APTO-253 in patients with relapsed or refractory hematologic malignancies. APTO-253 is a first-in-class inducer of the Krüppel-like factor 4 (KLF4) tumor suppressor gene, and the only clinical-stage compound targeted for patients with suppressed KLF4 levels.

"Epigenetic suppression of the KLF4 gene has been reported as a key transforming event in acute myeloid leukemia and high-risk myelodysplastic syndromes, and Aptose is a pioneer in advancing KLF4 induction as a new therapeutic approach for the treatment of these patient populations," commented William G. Rice, Ph.D., Chairman, President and CEO.

Aptose begins APTO-253 clinical study in patients with relapsed or refractory hematologic malignancies

Malaria combination drug therapy for children

A drug combination of artemisinin-naphthoquine should be considered for the treatment of children with uncomplicated malaria in settings where multiple parasite species cause malaria according to Tim Davis from University of Western Australia, Fremantle, Australia and colleagues in new research published in this week's PLOS Medicine.

The authors compared the current recommended therapy for uncomplicated malaria in children in Papua New Guinea, artemether-lumefantrine, with a different combination therapy, artemisinin-naphthoquine. Using a randomized, controlled trial study design including 186 children with Plasmodium falciparum infections and 47 children with Plasmodium vivax infections, the researchers found that artemisinin-naphthoquine was non-inferior to (no worse than) artemether-lumefantrine for treating Plasmodium falciparum (a difference of 2.2% [95% confidence interval ?3.0% to 8.4%] for reappearance of infection within 42 days) but was more effective for treating Plasmodium vivax (a difference 70.0% [95% confidence interval 40.9%-87.2%] for reappearance of infection within 42 days).

The authors conclude, "[t]he efficacy, tolerability, and safety of three daily doses of artemisinin-naphthoquine suggest that this regimen should be considered together with other currently available effective [artemisinin combination therapies] for treatment of uncomplicated malaria in [Papua New Guinea] and similar epidemiologic settings with transmission of multiple Plasmodium species."

Ref http://aac.asm.org/content/56/5/2465.full

Malaria combination drug therapy for children 

Drug stimulates brown fat, boosts metabolism

We know that, Mirabegron (formerly YM-178, trade name Myrbetriq, Betmiga in Spain) is a drug for the treatment of overactive bladder. It was developed by Astellas Pharma and was approved in the United States in July 2012.  Mirabegron activates the β3 adrenergic receptor in the detrusor muscle in the bladder, which leads to muscle relaxation and an increase in bladder capacity. 

Previous studies have found that brown fat can be coaxed into action by activating the β3-adrenergic receptor, which is expressed on the surfaces of brown and white fat cells, as well as on cells of the urinary bladder and other tissues. With these findings in mind, investigators wondered whether mirabegron, a drug that targets the β3-adrenergic receptor and was recently approved to treat overactive bladder, might help keep people's weight in check.

In all 12 men enrolled in the study, 200 milligrams of mirabegron led to higher brown fat metabolic activity, and at its peak level in the blood it increased the men's resting metabolic rate by 203 calories per day. While the dose was higher than the 50 milligram dose approved for overactive bladder, the treatment was well tolerated. All of the study participants were young, healthy individuals who had not previously taken mirabegron.

"Brown adipose tissue, or brown fat, produces β3-adrenergic receptor at levels higher than nearly every other organ in the body. We showed that a one-time dose of the drug mirabegron stimulates human brown adipose tissue so that it consumes glucose and burns calories," said lead author Dr. Aaron Cypess, who conducted the work at Joslin Diabetes Center and Beth Israel Deaconess Medical Center, affiliates of Harvard Medical School, and is now at the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.

The findings suggest that drugs that activate the β3-adrenergic receptor may be a promising treatment for obesity. "Prior to our work, the only known way to activate human brown adipose tissue was through cold exposure. While inexpensive, this approach is generally not well tolerated over the long term, and there is significant variability in people's responses," said Dr. Cypess. "In addition, once the cold exposure is removed, the effect usually turns off rather quickly."

Drug stimulates brown fat, boosts metabolism 

New version of common antibiotic could eliminate risk of hearing loss

"All I remember is coming out of treatment not being able to hear anything," said Bryce, now a healthy 14-year-old living in Arizona. "I asked my mom, 'Why have all the people stopped talking?'" He was 90 percent deaf.

"The loss has been devastating," said his father, Bart Faber. "But not as devastating as losing him would have been."

Treatment with aminoglycosides, the most commonly used class of antibiotics worldwide, is often a lifesaving necessity. But an estimated 20-60 percent of all patients who receive these antibiotics suffer partial or complete hearing loss.

Now, in a study that will be published online Jan. 2 in the Journal of Clinical Investigation, researchers at the Stanford University School of Medicine report that they have developed a modified version of an aminoglycoside that works effectively in mice without the risk of causing deafness or kidney damage, another common side effect.

The researchers hope to test versions of the modified antibiotic in humans as soon as possible.

"If we can eventually prevent people from going deaf from taking these antibiotics, in my mind, we will have been successful," said Anthony Ricci, PhD, professor of otolaryngology-head and neck surgery and co-senior author of the study. "Our goal is to replace the existing aminoglycosides with ones that aren't toxic."

Four years in the making

It took the scientists four years of research to produce 5 grams of the newly patented antibiotic, N1MS, which is derived from sisomicin, a type of aminoglycoside.

N1MS cured urinary tract infection in mice just as well as sisomcicin, but did not cause deafness, study results show. The study presents a promising new approach to generating a new class of novel, nontoxic antibiotics, Ricci said.

The two senior authors -- Ricci and Alan Cheng, MD, associate professor of otolaryngology-head and neck surgery -- joined forces in 2007 to explore the idea of creating new and improved versions of these antibiotics based on a simple yet groundbreaking idea born of Ricci's basic science research into the biophysics of how hearing works within the inner ear.

"It's a nice example of how basic science research is directly translatable into clinical applications," said Ricci.

Ricci is an expert on the process by which sound waves open ion channels within the sensory hair cells of the inner ear, allowing their conversion to electrical signals that eventually reach the brain.

Because aminoglycosides cause deafness by killing these nonregenerating hair cells, Ricci postulated, why not simply make the drug molecules unable to enter the cells' channels?

The idea made sense to Cheng.

"As a clinician-scientist, I treat kids with hearing loss," Cheng said. "When a drug causes hearing loss it is devastating, and it's especially disturbing when this happens to a young child as they rely on hearing to acquire speech.

"When I came to Stanford seven years ago from the University of Washington, I was exploring the angle that maybe we could add drugs to protect the ear from toxicity. Tony brought up this new idea: Why don't we just not let the drug get in? Great idea, I thought. When do we start to work?"

A potent antibiotic

For 20 years, and despite newer, alternative antibiotics, aminoglycosides have remained the mainstay treatment worldwide for many bacterial diseases, including pneumonia, peritonitis and sepsis. They also are often used when other antibiotics have failed to treat infections of unknown origins.

Their popularity is due, in part, to their low cost, lack of need for refrigeration and effectiveness at treating bacterial infections at a time when the declining potency of antibiotics is a major public health concern. They are frequently used in neonatal intensive care units to battle infections, or even the threat of infections, which pose a life-threatening risk for babies. Exactly how many premature babies suffer hearing loss as a side effect of treatment with the drug is unknown, Ricci said.

"The toxicity of these drugs is something we accept as a necessary evil," said Daria Mochly-Rosen, PhD, director of SPARK, a program at Stanford that assists scientists in moving their discoveries from bench to bedside.

Ref : http://dx.doi.org/10.1172/JCI77424

New version of common antibiotic could eliminate risk of hearing loss  

New treatment approach may improve survival rates for certain patients with stage 4 lung cancer

A clinical trial that combined stereotactic body radiation therapy with a specific chemotherapy regimen more than doubled survival rates for certain stage 4 lung cancer patients, UT Southwestern Medical Center cancer researchers report.

The combination of the chemotherapy regimen, erlotinib, with stereotactic body radiation therapy, known as SBRT, improved overall survival time to 20 months compared to historic 6- to 9- month survival times among erlotinib-only treated patients. The combination improved progression free survival - the time without the reappearance of cancer − from the historical two to four months to 14.7 months for similarly selected lung cancer patients.

"Our approach dramatically changed the pattern of relapse. We saw a shift in failure from existing, local sites to new, distant sites," said senior author Dr. Robert Timmerman, Director of the Annette Simmons Stereotactic Treatment Center, and Vice Chairman of Radiation Oncology at UT Southwestern. "This shift resulted in a surprisingly long remission from the reappearance of cancer in treated patients."

New treatment approach may improve survival rates for certain patients with stage 4 lung cancer

Honey offers new approach to fighting antibiotic resistance ............

In continuation of my update on Honey..

Honey, that delectable condiment for breads and fruits, could be one sweet solution to the serious, ever-growing problem of bacterial resistance to antibiotics, researchers said in Dallas* today. Medical professionals sometimes use honey successfully as a topical dressing, but it could play a larger role in fighting infections, the researchers predicted.

"The unique property of honey lies in its ability to fight infection on multiple levels, making it more difficult for bacteria to develop resistance," said study leader Susan M. Meschwitz, Ph.D. That is, it uses a combination of weapons, including hydrogen peroxide, acidity, osmotic effect, high sugar concentration and polyphenols -- all of which actively kill bacterial cells, she explained. The osmotic effect, which is the result of the high sugar concentration in honey, draws water from the bacterial cells, dehydrating and killing them.

In addition, several studies have shown that honey inhibits the formation of biofilms, or communities of slimy disease-causing bacteria, she said. "Honey may also disrupt quorum sensing, which weakens bacterial virulence, rendering the bacteria more susceptible to conventional antibiotics," Meschwitz said. Quorum sensing is the way bacteria communicate with one another, and may be involved in the formation of biofilms. In certain bacteria, this communication system also controls the release of toxins, which affects the bacteria's pathogenicity, or their ability to cause disease.

Meschwitz, who is with Salve Regina University in Newport, R.I., said another advantage of honey is that unlike conventional antibiotics, it doesn't target the essential growth processes of bacteria. The problem with this type of targeting, which is the basis of conventional antibiotics, is that it results in the bacteria building up resistance to the drugs.

Honey is effective because it is filled with healthful polyphenols, or antioxidants, she said. These include the phenolic acids, caffeic acid, p-coumaric acid and ellagic acid, as well as many flavonoids. "Several studies have demonstrated a correlation between the non-peroxide antimicrobial and antioxidant activities of honey and the presence of honey phenolics," she added. A large number of laboratory and limited clinical studies have confirmed the broad-spectrum antibacterial, antifungal and antiviral properties of honey, according to Meschwitz.

She said that her team also is finding that honey has antioxidant properties and is an effective antibacterial. "We have run standard antioxidant tests on honey to measure the level of antioxidant activity," she explained. "We have separated and identified the various antioxidant polyphenol compounds. In our antibacterial studies, we have been testing honey's activity against E. coli, Staphylococcus aureus and Pseudomonas aeruginosa, among others."

Honey offers new approach to fighting antibiotic resistance  

Newron, Zambon announce re-submission of safinamide NDA to FDA

In continuation of my update on safinamide 

Newron Pharmaceuticals S.p.A. ("Newron"), a research and development company focused on novel CNS and pain therapies, and its commercial and development partner Zambon S.p.A., an international pharmaceutical company, announced  that the NDA for safinamide has been re-submitted to the US FDA. This follows the announcement last week that the CHMP has given a positive opinion on safinamide for Europe.

The submission covers the indications "safinamide as add-on therapy to a stable dose of a single dopamine agonist" in early Parkinson's disease patients and "safinamide as add-on therapy to levodopa alone or in combination with other Parkinson's disease treatments" in mid-to late stage Parkinson's disease patients.

The first submission of safinamide to the US FDA was made in May 2014. On review, the FDA issued a Refusal to File (RTF) letter based on organizational and navigational problems, largely due relating to the hyperlinking of tables, folders and the organization of the table of contents in the submission.

Ravi Anand, Newron's CMO, stated: "Newron has been in frequent contact with the FDA to propose solutions to the technical issues and obtain their concurrence with the proposals. These discussions lead Newron to conclude that the RTF issues have been addressed in this submission."

Newron, Zambon announce re-submission of safinamide NDA to FDA

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Can-Fite BioPharma Ltd.  a biotechnology company with a pipeline of proprietary small molecule drugs that address inflammatory and cancer diseases, announced today that it completed the design of the Rheumatoid Arthritis (RA) Phase III study of its lead drug candidate CF101. Dr. M. Silverman, Can-Fite Medical Director, and Dr. Lee Simon, a key opinion leader in the field of autoimmune inflammatory diseases, designed the Phase III clinical study.

The Phase III study will be a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that will investigate the efficacy and safety of daily CF101 administered orally as a monotherapy for 12 weeks to patients with active RA. The study will have three arms, a 2 mg CF101 dose, a 3mg CF101 dose and placebo, given orally twice daily in the form of tablets. Approximately 300 patients are expected to be enrolled in the study, where sample size for each treatment group will be approximately 100 patients and will provide a statistical power of at least 90%. The study primary end point will be ACR 20 response at Week 12. The A3 adenosine receptor biomarker will be evaluated prior to treatment and its correlation to patients' response to the drug will be analyzed upon study conclusion.

Can-Fite BioPharma completes RA Phase III study of lead drug candidate CF101

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients

In continuation of my update on Bedaquiline

While an effective treatment is available for combating multidrug-resistant tuberculosis, it carries serious side effects for patients. New research conducted at the Center for Tuberculosis Research at the Johns Hopkins University School of Medicine shows that lower doses of the toxic drug bedaquiline — given together with verapamil, a medication that's used to treat various heart conditions — can lead to the same antibacterial effects as higher toxic doses of bedaquiline. The combination of the two drugs could potentially shorten treatment time, reduce the side effects of bedaquiline and improve patient outcomes for those suffering from TB.

The study will be published in the January 2014 issue of Antimicrobial Agents and Chemotherapy. The lead author is William Bishai, M.D., Ph.D., co-director of the Center for Tuberculosis Research.

"Using a mouse model of tuberculosis, we have shown lower doses of bedaquiline together with verapamil have the same antibacterial effect as the higher toxic doses," says Shashank Gupta, Ph.D., a research fellow at Johns Hopkins. "A lower dose of bedaquiline will cause no or less severe side effects."

Two years ago, bedaquiline became the first drug in the last four decades to be approved by the U.S. Food and Drug Administration for the treatment of multidrug-resistant TB. The drug works by inhibiting an enzyme used by Mycobacterium tuberculosis to replicate and spread throughout the body. While it can be a lifesaving therapy against one of the world's deadliest diseases, bedaquiline can also cause serious side effects in the heart and liver. Therefore, strategies to reduce the dose of bedaquiline while retaining its antibacterial activity would provide significant benefits to patients.

"Shortening treatment regimens and reducing the required doses may be a promising strategy to reduce the incidence of bedaquiline-related adverse effects and thereby improve multidrug-resistant TB treatment outcomes," says Gupta.

Combination of bedaquiline and verapamil reduces side effects, improves outcomes for TB patients