CURE NEWS: 03/16/2020

Existing antibiotic found to take out the root cause of Lyme disease

https://newatlas.com/medical/lyme-disease-antibiotic-cause-treatment/

http://archive.is/gQftT

Lyme disease is an infectious condition spread by ticks that affects as many as 300,000 people in the US every year, according to the Center for Disease Control and Prevention. Today's treatment is largely effective in treating the infection, but a good portion of patients do not respond and go on to endure lingering symptoms. A new study has revealed that an already-approved antibiotic can completely eliminate the underlying bacteria that causes the disease in mice, offering new hope of a more comprehensive therapy for humans.

While the standard antibiotics used to treat Lyme disease do the job for the majority of patients, somewhere between 10 and 20 percent go on to experience its symptoms. These include muscle pain, fatigue, fever, headaches and heart problems. There are couple of theories for why this might be.

“Some researchers think this may be due to drug-tolerant bacteria living in the body and continuing to cause disease,” said study author Jayakumar Rajadas. “Others believe it’s an immune disorder caused by bacteria during the first exposure, which causes a perpetual inflammation condition. Whatever the cause, the pain for patients is still very real.”

So the search is on for a treatment that kills off the disease in all recipients, and the scientists at Stanton have been working toward this aim for six years, screening around 8,000 different chemical compounds to build a list of candidates that were then tested in the lab and in mice. The one they have landed on is called azlocillin, and while it is not yet on the market, it has been approved by the US Food and Drug Administration.

The team found that of all the drugs they screened and tested, azlocillin proved most effective at killing off the bacteria that causes Lyme disease, called Borrelia burgdorferi. This was revealed through experiments in mice, where the animals were administered the drug at 7-, 14- and 21-day intervals and it completely killed off the infection. Significantly, the drug also proved effective in killing off drug-tolerant forms of B. burgdorferi in lab dishes.

“This compound is just amazing,” said Rajadas. “It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.”

The researchers have patented the compound for the treatment of Lyme disease and are working toward commercialization, with the next step being to conduct clinical trials.

The research was published in the journal Scientific Reports.

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https://med.stanford.edu/news/all-news/2020/03/potential-treatment-for-lingering-lyme-disease.html

http://archive.is/7ghDP

Potential treatment for Lyme disease kills bacteria that may cause lingering symptoms, study finds

Screening thousands of drugs, Stanford scientists determined that in mice, azlocillin, an antibiotic approved by the Food and Drug Administration, eliminated the bacteria that causes Lyme disease.

For decades, the routine treatment for Lyme disease has been standard antibiotics, which usually kill off the infection. But for up to 20% of people with the tick-borne illness, the antibiotics don’t work, and lingering symptoms of muscle pain, fatigue and cognitive impairment can continue for years — sometimes indefinitely.

A new Stanford Medicine study in lab dishes and mice provides evidence that the drug azlocillin completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness. The study suggests it could also be effective for treating patients infected with drug-tolerant bacteria that may cause lingering symptoms.

“This compound is just amazing,” said Jayakumar Rajadas, PhD, assistant professor of medicine and director of the Biomaterials and Advanced Drug Delivery Laboratory at the Stanford School of Medicine. “It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease.” Rajadas is the senior author of the study, which was published online March 2 in Scientific Reports. The lead author is research associate Venkata Raveendra Pothineni, PhD.

“We have been screening potential drugs for six years,” Pothineni said. “We’ve screened almost 8,000 chemical compounds. We have tested 50 molecules in the dish. The most effective and safest molecules were tested in animal models. Along the way, I’ve met many people suffering with this horrible, lingering disease. Our main goal is to find the best compound for treating patients and stop this disease.”

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Hunting for alternative drug

Frustrated by the lack of treatment options for Lyme disease patients with lingering symptoms, Rajadas and his team began hunting for a better alternative in 2011. In 2016, they published a study in Drug Design, Development and Therapy that listed 20 chemical compounds, from about 4,000, that were most effective at killing the infection in mice. All 20 had been approved by the Food and Drug Administration for various uses. One, for instance, is used to treat alcohol abuse disorder.

In this most recent study, azlocillin, one of the top-20 contenders, was shown to eclipse a total of 7,450 compounds because it is more effective in killing B. burgdorferi and causes fewer side effects. Lyme disease affects more than 300,000 people annually, according to the Centers for Disease Control and Prevention. It can affect various organs, including the brain, skin, heart, joints and nervous system, and cause heart problems and arthritis if untreated. Symptoms include fever, headaches, chills, and muscle and joint pain.

Traditional antibiotics, such as doxycycline, are effective as an early course of treatment for the infection in the majority of patients, but it remains unclear why these drugs fail to treat 10% to 20% of patients, Rajadas said.

“Some researchers think this may be due to drug-tolerant bacteria living in the body and continuing to cause disease,” said Rajadas, who is also a member of the Lyme Disease Working Group at Stanford. “Others believe it’s an immune disorder caused by bacteria during the first exposure, which causes a perpetual inflammation condition. Whatever the cause, the pain for patients is still very real.”

Azlocillin comes out on top

The drug, which is not on the market, was tested in mouse models of Lyme disease at seven-day, 14-day and 21-day intervals and found to eliminate the infection. For the first time, azlocillin was also shown to be effective in killing drug-tolerant forms of B. burgdorferi in lab dishes, indicating that it may work as a therapy for lingering symptoms of Lyme disease.

A researcher at Loyola College in India also contributed to the work.

The study was funded by the Bay Area Lyme Foundation and Laurel STEM Fund.

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>>8440871

Original study:

https://www.nature.com/articles/s41598-020-59600-4

http://archive.is/jBYvq

Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31

Results

Eradication of B. burgdorferi persisters by Azlocillin and Cefotaxime

In the present study, we first assessed the potency of azlocillin and cefotaxime against B. burgdorferi in dose dependent manner in both log and also stationary phase cultures of B. burgdorferi along with standard Lyme antibiotic (doxycycline). We used mitomycin C as a positive control and determined viability by colony forming unit (CFU) counts throughout the entire study19. Our results showed that the both tested antibiotics, cefotaxime at high concentration 40 μg/ml and azlocillin at very low concentration 2.5 μg/ml could able to completely (100%) kill log phase culture of B. burgdorferi respectively (Fig. 1A). Similarly, azlocillin at 20 μg/ml concentration also eliminated stationary phase B. burgdorferi persisters completely. However, cefotaxime at highest concentration of 80 μg/ml could able to kill (80%) of the stationary phase B. burgdorferi persisters (Fig. 1B). More importantly, cefotaxime at increased concentrations from 20 to 80 μg/ml did not vary much in killing of a small persister fraction of surviving cells. The doxycycline, a bacteriostatic couldn’t able to kill both the log phase and stationary phase B. burgdorferi cultures at higher concentrations of 80 μg/ml. More than 1000 stationary phase cells were survived at doxycycline concentration of 80 μg/ml. The mitomycin C at 1.25 µg/ml concentration killed B. burgdorferi both in log and stationary phase persisters as reported earlier19.

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