​STM antihypertensive drug brand new effect: can significantly improve the hearing loss of patients with benign brain tumors

Responsible editor | Neurofibromatosis type 2 (NF2) is a dominant hereditary tumor syndrome
.

Bilateral vestibular schwannoma (vestibular vestibular schwannoma, VS) is one of the characteristic manifestations of NF2
.

Hearing loss is the most specific symptom of NF2.
Vestibular schwannoma can cause sensorineural hearing loss (SNHL) in 95% of patients, which can cause patients to experience social communication, emotional expression, and language communication.
Obstacles may eventually lead to depression
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So far, the US Food and Drug Administration has not approved any treatment that can effectively improve the hearing function of patients
.

At present, the commonly used measures to improve hearing, such as hearing aids, cochlear implants, auditory brainstem implants, etc.
, have poor hearing recovery effects for NF2 patients
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The latest study by Lei Xu's team from Massachusetts General Hospital (MGH) shows that the antihypertensive drug losartan can help improve hearing impairment in patients with NF2.
This important result was published in Science on July 14, 2021.
Translational Medicine, entitled Losartan prevents tumor-induced hearing loss and augments radiation efficacy inNF2 schwannoma rodent models
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For a long time, the biggest obstacle to the treatment of NF2-related hearing loss is that we have not fully understood the pathophysiological mechanism of how tumors cause hearing loss
.

A previous study showed that fibrosis in vestibular schwannoma is related to hearing loss, which prompted the team to try to explore the effectiveness of drugs that block fibrosis in improving hearing impairment
.

Losartan blocks a component of the renin-angiotensin system, which is not only involved in regulating blood pressure, but also in the occurrence and development of fibrosis and inflammation
.

Angiotensin receptor antagonist drugs including Losartan have been shown to reduce collagen accumulation in heart and kidney fibrotic diseases
.

Dr.
Xu's team found that losartan treatment can improve the hearing of NF2 tumor-bearing mice
.

Further analysis of the NF2-/- tumor model, they found that in the NF2 mouse model, losartan treatment has multiple effects on the tumor and nervous system: 1.
Losartan can reduce the degree of tumor fibrosis; 2.
Losartan Tan can inhibit neuroinflammation IL6/STAT3 and TLR4 signaling pathways; 3.
Losartan can promote blood vessel normalization and reduce neuroedema; 4.
Losartan can improve tumor hypoxia and increase the sensitivity of radiotherapy, which is helpful To reduce the radiation dose required to control tumor growth, thereby reducing further hearing damage caused by high-dose radiation therapy
.

The high expression of tumor-derived IL-6 leads to the reduction of cochlear sensory cells and nerve cells.
In order to prepare to translate these findings into clinical applications, using NF2 patient samples and treatment data, the article found: 1.
Tumor inflammatory signals can directly destroy hearing is critical Important cochlear cells
.

2.
Compared with patients taking other antihypertensive drugs or not taking antihypertensive drugs, NF2 patients taking losartan angiotensin receptor antagonist antihypertensive drugs did not see further hearing loss during the follow-up
.

These research results and findings support the preventive and protective effects of Losartan on the hearing function of NF2 patients, and provide an extremely important theoretical basis for the development of prospective clinical trials
.

Professor Lei Xu said, “As one of the most commonly used prescription drugs for hypertension, the safety and low cost of losartan can ensure that the research can be quickly transformed into clinical trials to prevent sensorineural hearing loss caused by tumors and make vestibular Patients with schwannoma benefit"
.

Losartan prevents hearing damage caused by schwannoma and enhances the potential mechanism of tumor radiotherapy sensitivity
.

Losartan "normalizes" the tumor microenvironment through the following aspects: 1.
Reduce the inflammatory cytokines produced by macrophages, thereby reducing the production of ototoxic reactive oxygen species
.

2.
Promote the normalization of blood vessels, thereby reducing nerve edema
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Therefore, Losartan prevents hearing damage by reducing neuroinflammatory response and edema
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3.
Reduce extracellular matrix components, reduce the compression of tumor blood vessels, and make blood vessels have better perfusion and oxygen delivery functions
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Since oxygen is a powerful radiotherapy sensitizer, losartan can effectively enhance the sensitivity of radiotherapy
.

Original link: https://stm.
sciencemag.
org/lookup/doi/10.
1126/scitranslmed.
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.