Peripheral Focused Ultrasound Stimulation
Peripheral focused ultrasound stimulation (pFUS) is a non-invasive therapeutic modality, currently in early clinical trials, that employs ultrasonic waves to target organ and sub-organ innervation points for neuromodulation.[1][2] pFUS has the ability to provide precise intervention without the need for incisions or radiation, making it a potentially safe means of neuromodulation. Research is ongoing into its safety profile. Initial research shows side effects akin to diagnostic ultrasound treatment.[3] Its application includes treating conditions like rheumatoid arthritis, glucose dysregulation, and cytokine storms.[1][2]
Historical Development: Relation to Vagus Nerve Stimulation
The NIH SPARC and DARPA ElectRx programs sought to advance the state of bioelectric medicine.[4][5] Central to these efforts was investigating stimulation of the vagus nerve for neuromodulation. Electrical stimulation of the vagus nerve could activate neural pathways, but imprecise stimulation could also activate unintended nerve branches and neural pathways. Exploring the use of ultrasound as an alternative to electricity, it is possible to stimulate the vagus nerve with acoustic waves, but it is also possible to stimulate nerve bodies and terminals that are distal to the vagus nerve while avoiding both adjacent nerve branch activation and a need for invasive procedures, opening up an alternative to vagus nerve stimulation (VNS) or traditional pharmacological options for treating epilepsy, depression, and certain inflammatory conditions.[3]
Splenic Ultrasound and the Cholinergic Anti-inflammatory Pathway
pFUS's use cases include the splenic region, where it can activate the Cholinergic Anti-inflammatory Pathway (CAP). Rheumatoid arthritis, a chronic inflammatory disorder, has been shown to respond to splenic ultrasound by way of CAP modulation. By targeting the spleen with pFUS, it's possible to reduce the production of inflammatory cytokines, providing relief from inflammation and associated symptoms.[6]
In cytokine storms caused by endotoxin exposure, controlling the inflammatory response can save healthy tissue from undue harm. pFUS, through its action on the spleen and the CAP, offers a potential therapeutic to manage and possibly prevent cytokine storms while still allowing for a non-systemic inflammatory response as well as an adaptive immune response.[7]
Liver Ultrasound and Glucose Homeostasis
The liver plays a pivotal role in maintaining glucose homeostasis. Recent studies have shown potential for pFUS neuromodulation of the liver to maintain or restore glucose homeostasis. In conditions like type 2 diabetes, porta hepatis stimulation can enhance insulin sensitivity and reduce circulating glucose, offering a novel non-pharmacological approach to manage diabetes.[8]
In conditions like endotoxin hyperinsulinemia, where there's an excessive release of insulin due to bacterial endotoxins, pFUS has shown promise in regulating insulin levels, further suggesting its potential in metabolic regulations.[9]
Safety Profile and Current Trials
Understanding pFUS has evolved from small to large mammal trials as well as to phase 1 human trials.
Rodent and swine models: Initial trials in rat models have shown that pFUS, when applied at intended doses, does not cause damage or adverse side effects beyond what is caused by diagnostic ultrasound.[8][10] Preliminary results in pigs indicate a favorable safety profile, paving the way for human trials.[11][12]
Human trials: an initial type 2 diabetes trial suggests pFUS treatment of the liver is safe and ready for larger scale tests. An initial rheumatoid arthritis study suggests vagus nerve stimulation is safe and ready for longer application with more patients. Human trials for pFUS CAP activation (involving ex vivo endotoxin exposure or directly treating severely ill hospital patients) suggest treating inflammation from endotoxin exposure is as safe as diagnostic ultrasound, and is ready for larger clinical trials.[1][2][7][13]
This article "Peripheral Focused Ultrasound Stimulation" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Peripheral Focused Ultrasound Stimulation. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
- ↑ 1.0 1.1 1.2 Zanos, Stavros; Ntiloudi, Despoina; Pellerito, John; Ramdeo, Richard; Graf, John; Wallace, Kirk; Cotero, Victoria; Ashe, Jeff; Moon, Jessica; Addorisio, Meghan; Shoudy, David; Coleman, Thomas R.; Brines, Michael; Puleo, Chris; Tracey, Kevin J.; Chavan, Sangeeta S. (2023). "Focused ultrasound neuromodulation of the spleen activates an anti-inflammatory response in humans". Brain Stimulation. 16 (3): 703–711. doi:10.1016/j.brs.2023.04.003. ISSN 1935-861X.
- ↑ 2.0 2.1 2.2 Ashe, J.; Graf, J.; Madhavan, R.; Wallace, K.; Cotero, V.; Abate, S.; Pandey, RK.; Herzog, R.; Porindla, SN.; Shoudy, D.; Fan, Y.; Kao, TJ.; Puleo, C. (2023-09-12). "Investigation of liver-targeted peripheral focused ultrasound stimulation (pFUS) and its effect on glucose homeostasis and insulin resistance in type 2 diabetes mellitus: a proof of concept, phase 1 trial". QJM. 116 (8): 667–685. doi:10.1093/qjmed/hcad098. PMID 37243693 Check
|pmid=value (help). - ↑ 3.0 3.1 Blackmore, J.; Shrivastava, S.; Sallet, J.; Butler, CR.; Cleveland, RO. (July 2019). "Ultrasound Neuromodulation: A Review of Results, Mechanisms and Safety". Ultrasound Med Biol. 45 (7): 1509–1536. doi:10.1016/j.ultrasmedbio.2018.12.015. PMC 6996285 Check
|pmc=value (help). PMID 31109842. - ↑ "Stimulating Peripheral Activity to Relieve Conditions (SPARC)". National Institutes of Health (NIH). Retrieved October 25, 2023.
- ↑ "Electrical Prescriptions (ElectRx)". Defense Advanced Research Projects Agency (DARPA). Retrieved October 25, 2023.
- ↑ Cotero, V.; Graf, J.; Zachs, D.P.; Tracey, K.J.; Ashe, J.; Lim, H.H.; Puleo, C. (August 2019). "Peripheral Focused Ultrasound Stimulation (pFUS): New Competitor in Pharmaceutical Markets?". SLAS Technol. 24 (4): 448–452. doi:10.1177/2472630319849383. PMC 7171588 Check
|pmc=value (help). PMID 31226243. - ↑ 7.0 7.1 Graham, Rachel S.; Zachs, Daniel P.; Cotero, Victoria; D’Agostino, Catherine; Ntiloudi, Despoina; Kaiser, Claire R.W.; Graf, John; Wallace, Kirk; Ramdeo, Richard; Coleman, Thomas R.; Ashe, Jeffrey; Pellerito, John; Tracey, Kevin J.; Binstadt, Bryce A.; Chavan, Sangeeta S.; Zanos, Stavros; Puleo, Christopher; Peterson, Erik; Lim, Hubert H. (2020). "First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation". medRxiv. doi:10.1101/2020.07.14.20153528.
- ↑ 8.0 8.1 Huerta, T.S.; Devarajan, A.; Tsaava, T.; Rishi, A.; Cotero, V.; Puleo, C.; Ashe, J.; Coleman, T.R.; Chang, E.H.; Tracey, K.J.; Chavan, S.S. (2021-03-03). "Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions". Sci Rep. 11 (1): 5083. doi:10.1038/s41598-021-84330-6. PMC 7930257 Check
|pmc=value (help). PMID 33658532 Check|pmid=value (help). - ↑ Cotero, V.; Fan, Y.; Tsaava, T. (2019). "Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation". Nat Commun. 10: 952. doi:10.1038/s41467-019-08750-9.
- ↑ Zachs, D.P.; Offutt, S.J.; Graham, R.S. (2019). "Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis". Nat Commun. 10: 951. doi:10.1038/s41467-019-08721-0.
- ↑ Czura, CJ.; Schultz, A.; Kaipel, M.; Khadem, A.; Huston, JM.; Pavlov, VA.; Redl, H.; Tracey, KJ. (June 2010). "Vagus nerve stimulation regulates hemostasis in swine". Shock. 33 (6): 608–13. doi:10.1097/SHK.0b013e3181cc0183. PMC 2921076. PMID 19953009.
- ↑ Cotero, V.; Graf, J.; Miwa, H. (June 2022). "Stimulation of the hepatoportal nerve plexus with focused ultrasound restores glucose homoeostasis in diabetic mice, rats and swine". Nature Biomedical Engineering. 6 (6): 683–705. doi:10.1038/s41551-022-00870-w. PMC 10127248 Check
|pmc=value (help). PMID 35361935 Check|pmid=value (help). - ↑ "UMN-GE clinical trial investigating splenic stimulation to treat COVID-19". ClinicalTrials.gov. Retrieved October 11, 2023.
