Modern medicine continues to make significant strides in treating neurodegenerative diseases. Recent clinical trials using focused ultrasound and microbubbles to enhance drug delivery to the brain in patients with Alzheimer’s and Parkinson’s diseases have shown high efficacy in mice. This innovative approach opens new horizons in the fight against such complex diseases.
The blood-brain barrier is a thin membrane that separates the central nervous system (brain and spinal cord) from the circulatory system. It prevents the penetration of molecules with a diameter greater than 400, which protects the brain from toxins but also limits the delivery of medications. This has become one of the key challenges in developing effective treatments for patients with Parkinson’s and Alzheimer’s diseases.
Microbubbles are synthesized substances the size of a human erythrocyte, which are administered intravenously. They safely circulate in the circulatory system and interact with focused ultrasound, creating temporary openings in the walls of blood vessels. These openings allow medicinal substances to penetrate the brain, which was previously impossible.
Researchers from Columbia Engineering conducted a groundbreaking study using transcranial focused ultrasound in combination with microbubbles They administered neurotrophic factors—molecules that support the growth and survival of neurons, such as glial cell line-derived neurotrophic factor and neurturin These substances previously showed a positive effect in animal models of Parkinson’s disease
Scientists used an early-stage Parkinson’s disease model in mice to test whether the delivery of neurotrophic factors improves in key brain areas such as the substantia nigra and dorsal striatum. The results showed that the combination of focused ultrasound and microbubbles significantly increased drug penetration into the brain, leading to an increase in the number of nerve cells and fibers, as well as elevated dopamine levels.
«This is the first case where anyone has been able to restore the dopaminergic pathway using available drugs in the early stages of Parkinson’s disease,” noted E. Konofagou, the lead author of the study. This research demonstrates that the use of focused ultrasound in the early stages of Parkinson’s disease not only slows the progression of neurodegeneration but also improves neuronal functions.
The results also open new therapeutic opportunities for treating other central nervous system diseases, such as Alzheimer’s disease. The use of focused ultrasound and microbubbles may become the key to creating effective methods for drug delivery to the brain.
Until recently, patients with Parkinson’s disease did not have such effective treatment methods as levodopa or deep brain stimulation. Today, we actively use MRI-guided focused ultrasound for treating tremor and rigidity. In the near future, this method may become the basis for improving drug delivery in Parkinson’s disease, opening new horizons in the fight against this ailment.
Research using focused ultrasound and microbubbles offers hope to millions of patients worldwide. This innovative method not only improves drug delivery but may also become the foundation for treating the most complex neurodegenerative diseases. We live in an era where research and medicine unite to change patients’ lives for the better.
Improving Drug Therapy Penetration into the Substantia Nigra Using Focused Ultrasound in Early Parkinson’s Disease. Research Rationale: Under the influence of focused ultrasound, intravenously administered microbubbles microbubles) cause a reversible opening of the blood-brain barrier, allowing medications to penetrate the brain and exert therapeutic effects, but only in specific areas where therapeutic intervention is needed
Clinical trials using focused ultrasound and microbubbles to enhance drug therapy penetration into the brain for patients with Alzheimer’s disease have shown high efficacy. Brief Information: The blood-brain barrier is a thin membrane that separates the central nervous system (brain and spinal cord) from the circulatory system and prevents the penetration of molecules with a diameter greater than 400. However, many drugs do not pass this barrier due to the mass of their molecules. Microbubbles ( microbubbles) – rounded substances synthesized from protein, the size of a human erythrocyte, which are injected intravenously into the circulatory system and safely circulate through the bloodstream. Their surface reflects directed ultrasound and damages the blood vessel wall. Through the resulting opening, medicinal substances penetrate the brain matter [1]. Inability to overcome the blood-brain barrier with medications hinders the development of successful treatment methods for patients with neurodegenerative disorders such as Parkinson’s disease. Seeking to improve treatment delivery to the brain, a team from Columbia Engineering used transcranial focused ultrasound combined with intravenously administered microbubbles containing neurotrophic factors to create temporary openings in the blood-brain barrier. Neurotrophic factors are a family of molecules, mainly small proteins, that support the growth, survival, and differentiation of both developing and mature neurons. In the study, glial cell line-derived neurotrophic factor and neurturin were used as neurotrophic substances, which had positive effects in animal models of Parkinson’s. Previously, researchers had already proven that focused ultrasound facilitated the delivery of neurturin to key areas responsible for the development of Parkinson’s disease in the brains of mice. Scientists used an early-stage Parkinson’s disease model in mice to test whether the delivery of neurotrophic substances to the substantia nigra and dorsal striatum improved under the influence of focused ultrasound and microbubbles. Unlike ultrasound or neurotrophic factors alone, their combination reduces damage, allowing these molecules to penetrate the brain. Researchers found an increase in the number of nerve cells and nerve fibers, as well as an increase in dopamine levels with the use of combined treatment. The results of this study suggest that the application of focused ultrasound in the early stages of Parkinson’s disease improves the delivery of neurotrophic substances to the brain, which block the rapid progression of neurodegeneration while simultaneously improving neuron function. “This is the first time anyone has been able to restore the dopaminergic pathway with available drugs in the early stages of Parkinson’s disease,” said E. Konofagou, the lead author of the study in a press release. The study showed that the use of focused ultrasound combined with intravenous injection of microbubbles improved the penetration of drug therapy into the brains of mice induced with an early form of Parkinson’s disease. This research opens new therapeutic opportunities for the early treatment of central nervous system diseases!
https://www.bme.columbia.edu/news/konofagou-ultrasound-dopaminergic-pathway
Karakatsani, M.E., Wang, S., Samiotaki, G., Kugelman, T., Olumolade, O.O., Acosta, C., Sun, T., Han, Y., Kamimura, H.A., Jackson-Lewis, V. and Przedborski, S., 2019. Amelioration of the nigrostriatal pathway facilitated by ultrasound-mediated neurotrophic delivery in early Parkinson’s disease. Journal of Controlled Release, 303, pp.289-301. https://www.sciencedirect.com/science/article/abs/pii/S0168365919301907
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