July 15, 2024

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World’s First Inhalable Heart Repair Medication Unveiled

World’s First Inhalable Heart Repair Medication Unveiled



World’s First Inhalable Heart Repair Medication Unveiled

In the human body, the heart and lungs function as intimate allies, their cooperation essential for optimal performance.

Any dysfunction in one can adversely affect the other; for instance, in heart failure, decreased pumping function may lead to fluid accumulation in the lungs, causing respiratory difficulties.

Conversely, conditions like chronic obstructive pulmonary disease can increase the burden on the heart, potentially resulting in cardiac issues.

So, when the heart faces challenges, can the lungs provide a solution?

Scholars from Italy and Germany, leveraging nanotechnology, have developed an inhalable medication named LungToHeartNIM for treating heart failure. Experimental results based on a pig pathological model were recently published in the “Journal of the American College of Cardiology.”

LungToHeartNIM carries simulated peptides targeting heart failure treatment. Pigs with heart failure showed improved cardiac contraction function and fibrosis after receiving low-dose LungToHeartNIM treatment for two weeks. The left ventricular ejection fraction increased by approximately 17%, demonstrating good tolerance.

This marks the first set of data since the inception of LungToHeartNIM, representing a significant milestone in the field of molecular treatment for heart failure. It is the first time the effectiveness of peptide modulation targeting calcium channels has been proven in a clinically relevant large animal heart failure model.

World's First Inhalable Heart Repair Medication Unveiled

Molecular therapy presents enormous potential in the cardiovascular disease treatment domain. Scientists have identified multiple critical treatment targets within heart cells and are devising methods to develop therapies using viral or non-viral carriers, aiming the arrows directly at the heart.

However, current administration methods primarily involve various injections, which are invasive and cumbersome. Is there a more direct and efficient way to deliver medication to heart cells?

The L-type calcium channel (LTCC), responsible for the flow of calcium ions within cells, has been shown to be compromised in diseases like heart failure. Previous studies indicated that the use of simulated peptides (MP) could salvage impaired LTCC, thereby improving myocardial contraction ability and heart function in heart failure patients.

To deliver simulated peptides directly to the heart, researchers embedded calcium phosphate nanoparticles containing the peptide (CaP-MP) into inhalable dry powder particles (dpCaP-MP). This pioneering development resulted in the creation of LungToHeartNIM, an inhalable heart repair medication that allows the drug to reach the heart through the respiratory tract rather than arterial transport.

In this preclinical experiment, the researchers validated the functionality and tolerance of LungToHeartNIM using a pig model of heart failure (left ventricular ejection fraction = 30%±8%).

Results showed that daily inhalation of a dose of 0.015mg/kg LungToHeartNIM for at least two weeks reshaped the hearts of the affected pigs, improving contraction function. The left ventricular ejection fraction increased by 17%±6%, left ventricular enlargement decreased, ventricular-arterial coupling (VAC) improved, pulmonary congestion reduced, and the blood levels of heart failure marker NT-proBNP were comparable to those of healthy pigs.

Histological biopsy results indicated a reduction in fibrosis in the treated pigs’ hearts, an increase in mitochondrial volume and quantity within cardiac cells, and the restoration of LTCC expression to normal levels.

Additionally, using proteomic analysis techniques, the researchers found 98 differentially expressed proteins between heart failure pigs and healthy pigs. After LungToHeartNIM treatment, the overall protein expression pattern shifted towards a healthier state.

LungToHeartNIM exhibited excellent tolerance, with no significant adverse events during treatment. The treated pigs showed no significant differences in respiratory rate, heart rate, weight change, blood cell count, liver and kidney function indicators, or other blood parameters compared to healthy pigs—all within normal ranges.

In cardiovascular disease research, pigs are often used for experimentation due to their high anatomical, size, and functional similarity to human hearts. Based on the results of this study, the clinical translation of LungToHeartNIM appears promising. This non-invasive delivery method from the lungs to the heart not only simplifies the treatment process but also avoids the discomfort and potential complications associated with current invasive treatments.

The researchers indicate that future work will further describe the pharmacokinetics of the simulated peptides carried by LungToHeartNIM in the body, including absorption, distribution, metabolism, and excretion. This breakthrough therapy holds great promise for heart failure patients.

World’s First Inhalable Heart Repair Medication Unveiled

References:

[1]https://www.jacc.org/doi/10.1016/j.jacc.2023.10.029

[2]Hulot, J. S., & Kupatt, C. (2024). Inhalable Therapies for the Heart: Take the “Lung” Way Home?. Journal of the American College of Cardiology, 83(1), 60–62. https://doi.org/10.1016/j.jacc.2023.10.028

[3]https://www.businesswire.com/news/home/20240102040478/en

(source:internet, reference only)


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