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MicuRx Pharmaceuticals Announces Promising Results From MRX-5 Study For Treating Mycobacterium Abscessus Infections

FOSTER CITY, Calif., Oct. 8, 2024 /PRNewswire/ -- MicuRx Pharmaceuticals is excited to announce the publication of groundbreaking research on MRX-5, a novel oral oxaborole prodrug, demonstrating significant potential in the treatment of pulmonary infections caused by Mycobacterium abscessus (Mab), a severe nontuberculous mycobacterium (NTM) infection. The research was led by Dr. Gyanu Lamichhane, Associate Professor at Johns Hopkins University School of Medicine.

The study, published in Antimicrobial Agents and Chemotherapy, evaluated MRX-5 against clinical isolates of M. Abscessus in a validated mouse model. The results revealed that MRX-5 achieved a dose-dependent reduction in lung bacterial burden, with dose of 15 mg/kg showing efficacy comparable to the current standard-of-care.

Key Findings:

MRX-5 demonstrated significant efficacy against a variety of M. Abscessus isolates, including drug-resistant strains, offering hope for patients with limited treatment options.

At dose of 15 mg/kg, MRX-5 achieved a reduction in lung bacterial loads comparable to established therapies.

MRX-5 showed dose-linear pharmacokinetics, indicating the potential for predictable and manageable dosing in clinical settings.

The study marks the first evaluation of MRX-5, the oral prodrug of MRX-6038, in an animal model, demonstrating MRX-5 is well tolerated and effective over extended treatment durations.

"We are excited about the potential of MRX-5 to provide a much-needed new treatment option for patients suffering from Mycobacterium abscessus infections," said Jerry Li, the President of MicuRx Pharmaceuticals. "The oral formulation of MRX-5 represents a critical advancement in NTM therapy, particularly for vulnerable patient populations, including those with cystic fibrosis, bronchiectasis, and immunosuppression, who struggle with existing treatment regimens."

Mab infections are notoriously difficult to treat, often requiring prolonged, complex, and poorly tolerated courses of multiple antibiotics. With no FDA-approved treatment for Mab, the results of this study are a promising step towards addressing the growing unmet clinical need for effective and convenient treatment options. Importantly, MRX-5 offers an oral alternative to current treatment regimens that are primarily intravenous and highly toxic, with failure rates exceeding 50%. MRX-5 could vastly improve patient compliance and quality of life compared to the current standard intravenous therapies.

MicuRx Pharmaceuticals is committed to advancing the development of MRX-5 and looks forward to initiating clinical trials in patients to further evaluate its safety and efficacy in human subjects.

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For more information, please contact:MicuRx Pharmaceuticals, Inc.Email: info@micurx.Com Website: www.Micurx.Com

About MicuRx PharmaceuticalsMicuRx Pharmaceuticals is a biopharmaceutical company focused on the discovery, development, and commercialization of innovative antibiotics for the treatment of multidrug-resistant infections. With a mission to address significant unmet medical needs, MicuRx is advancing a portfolio of drug candidates targeting difficult-to-treat infections.

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Modified Plant Compound Shows Promise As Next Weapon In Fight Against Drug-resistant TB

A modified compound taken from bloodroot, a wildflower native to North America, effectively fights multidrug-resistant tuberculosis (TB) bacteria in the test tube, according to a new study. 

The discovery, published in Microbiology Spectrum, shows promise for further testing with the ultimate goal of finding new drugs to treat TB, the leading infectious killer after COVID-19, according to the World Health Organization. 

"There's an urgent need to improve our pipeline of drugs to address multidrug-resistant strains of TB, to either reduce the required treatment time or tackle the development of resistance," said senior author Dr. Jim Sun, assistant professor in the UBC department of microbiology and immunology. "The drugs currently used for treatment are more than 50 years old. Unlike other bacterial infections, treating tuberculosis takes at least six months using a combination of drugs, which puts significant strain on the human body."

Synthesized from bloodroot 

To find new potential candidates for TB treatment, the researchers looked to sanguinarine, a compound extracted from the bloodroot plant which has known antimicrobial and antiseptic properties. 

Compounds derived from natural sources are great candidates for anti-infection drug development, but also tend to be more toxic to humans. The research team modified sanguinarine to increase its potency and reduce its toxicity, creating 35 new derivatives including two – BDP9 and BPD6 – that inhibited growth of Mycobacterium tuberculosis, the bacterium that causes TB, by more than 90 per cent even at relatively low doses in the test tube.

Both compounds were effective against three particularly aggressive TB strains and five strains resistant to several current antibiotic treatments, the researchers said. 

When tested in mice models infected with a weakened animal strain of TB, BPD9 significantly reduced bacterial presence in the lungs within just eight days.

"We were thrilled to see that the BPD compounds were effective even against multidrug-resistant strains. We look forward to investigating further how they work compared to existing antibiotics," said first author Yi Chu Liang, a UBC and University of Ottawa doctoral student.

Stops TB coming back to life

The researchers believe BPD9 may also be effective in treating dormant TB. "TB treatment takes six months because the bacteria can 'hibernate' in your lungs until reactivated. Most antibiotics work best against actively growing bacteria, but BPD9 seems to be able to stop dormant bacteria from coming back to life," said Dr. Sun. The BPD compounds also targeted the mycobacteria family specifically, leaving other types of bacteria unharmed and so, protecting the health of the human microbiome. 

This specific activity also included non-tuberculous mycobacteria which are recognized as pathogens of concern. "Some species are notoriously resistant to the antibiotics available and the treatment outcomes are poor, especially in patients with pre-existing lung disease," said co-first author Dr. Andréanne Lupien, assistant professor, department of microbiology and immunology at McGill University. "For these hard-to-treat infections, the development and the evaluation of new therapeutic options, like BPD9, with a novel mechanism of action is paramount."

Further research needed

While these preclinical results are promising, the researchers say there's still much work to be done. Next steps will include further reducing the toxicity of the compounds, optimizing their activity, and conducting further testing using drug-resistant strains of the TB-causing bacteria. 

The research team will also work to figure out how the BPD compounds work within the bacteria, to enhance the effectiveness of any resulting drug.

Researchers Discovered Mechanism Driving Immune Perturbations After Severe Infections

Researchers at Baylor College of Medicine and collaborating institutions have discovered a mechanism that drives the long-term decline in immune response that is observed after tuberculosis (TB) has been successfully treated. Their findings, published in the Proceedings of the National Academy of Sciences, suggest a potential new way to restore immune responsiveness and reduce mortality risk after severe infections.

"Sepsis, the body's extreme response to an infection, and TB are associated with loss of protective immune responses and increased mortality post successful treatment," said Dr. Andrew DiNardo, corresponding author and associate professor in the section of infectious diseases and division of pediatric global and immigrant health at Baylor College of Medicine and Texas Children's Hospital. "In the current study, we investigated what mediated the perturbation of immune function after severe infections."

Researchers knew that severe and chronic infections in humans and animals result in persistent epigenetic changes. These changes refer to alterations in chemical markings on the DNA that tell cells in the body which genes to turn on or off.

For instance, TB dampens immune responsiveness by adding extra methyl chemical tags (DNA methylation) to certain genes involved in immune responses. Consequently, the body produces fewer proteins mediating immune defense which increases susceptibility to infections. However, the mechanisms inducing epigenetic changes in infections were not clear.

TCA plays a role in epigenetic changes

Previous studies have identified the tricarboxylic acid (TCA) cycle, a key part of cellular metabolism, as a metabolic driver of the epigenetic landscape in cancer. DiNardo and his colleagues wanted to see if TCA also regulated epigenetics, specifically DNA methylation, after infection-induced immune tolerance.

The team reported that human immune cells treated in the lab with bacterial lipopolysaccharide, a bacterial product, and Mycobacterium tuberculosis, the bacteria that cause TB, became immune tolerant.

They also found that patients diagnosed with both sepsis and TB have increased TCA activation, which correlates with DNA methylation. When TB patients were given the standard care of therapy and antibiotics, plus everolimus, an inhibitor of TCA activation, the damaging methylation changes to their DNA were reduced, which suggests that it can help restore the immune system after severe infections.

"Tuberculosis is an interesting disease. By the time a person is diagnosed, they have had symptoms for over three months. But seeing that adding everolimus to standard TB antibiotic treatment reduces the number of detrimental DNA methylation marks six months into the disease is promising that we can induce epigenetic healing," DiNardo said.

"What we found is going to lead to a paradigm shift," said Dr. Cristian Coarfa, co-author and associate professor of molecular and cellular biology at Baylor. "Our approaches are not limited to tuberculosis. The evidence we have and what we are trying to build on suggests that these strategies might play a role in other infectious diseases."

The next step for the researchers is to identify which post-TB epigenetic marks are leading to increased morbidity and mortality. From there, they would like to determine which individuals would benefit the most from a host-directed therapy that can heal epigenetic scars.

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