There are many types of rare genetic diseases, and most of them have different pathogenic mechanisms. However, the National Institutes of Health (NIH) recently discovered that a toxic protein produced by the human body may be the cause of two completely different rare genetic diseases. the cause of the disease, in therare diseaseWhile the development of new treatments finds new directions, it also leaves more questions for scientists to explore.
DUX4 is the culprit of two rare diseases?
(facioscapulohumeral muscular dystrophy, FSHD) is a hereditary muscular dystrophy, which can cause progressive weakness of muscles in specific parts such as the face and shoulder blades. On the other hand, congenital arhinia is caused by external nose, olfactory bulb ( A rare facial defect caused by restricted development of olfactory bulbs and olfactory tracts.
Both FSHD type 2 and congenital anatomy are caused by SMCHD1 Caused by genetic mutations, in the case of FSHD type 2, known progressive muscle weakness associated with SMCHD1 The mutation is related to the loss of the expression ability of the toxin protein DUX4, and the NIH team further found in the new study that DUX4 is actually responsible for the killing of nose precursor cells in congenital anatomy.
Through induced pluripotent stem cells obtained from patients with two diseases (iPSC), the researchers were able to study the cranial placode cells responsible for the development of the body’s sensory organs. They found that as the cranial placode cells began to form, the expression of DUX4, which led to cell death, also occurred. The team then further found that , when the mutation SMCHD1 Combining the gene with environmental regulators such as viruses may amplify the expression of DUX4, which may be the underlying cause of congenital anomalies.
Exploring how DUX4 selectively causes cell death
From the research point of view, congenital anatomy, like FSHD type 2, is due to the original inhibition of DUX4 in a specific cellular environment. SMCHD1 However, the team still does not know why nasal cells are not persecuted in facioscapulohumeral muscular dystrophy and why muscle cells are not persecuted in congenital anatomy.
Going forward, the team hopes to try to figure out the more downstream players in the DUX4 expression pathway, try to find a way to block the key to destroying muscle cells or nose precursor cells, and provide relevant information.rare diseaseof patients find more directions for the development of new treatment options.
Further reading: Sanofi, miRecule sign cooperation agreement to jointly develop RNA complex therapy for rare muscle wasting disease
References:
1. Science Advances, 2023, https://www.science.org/doi/10.1126/sciadv.abq7744
2. https://www.nih.gov/news-events/news-releases/toxic-protein-linked-muscular-dystrophy-arhinia
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