The mother sent 50 SCI articles in a row, but did not save her son's life. Have you heard of this terrible disease?

time:2023-02-07 author:Cry
The mother sent 50 SCI articles in a row, but did not save her son's life. Have you heard of this terrible disease?

*For medical professional reading reference

7 years old, 70 years old body.

Leslie Gordon is an ordinary clinician whose peaceful life was disrupted by the birth of her son. Her child, Sam Burns, was born with a rare disease called Progeria (HGPS), which affects only 1:8 million to 1:4 million. The disease causes her children to age faster than normal, and patients often end up dying from complications, with an average lifespan of just 14.6 years. Since HGPS is an extremely rare disease in the clinic, and there is no precedent for research in the world, in order to save the child, Leslie organized and led a team to try to find the causative gene of this disease, so as to develop drugs, and constantly overcome difficulties. , and published 50 SCI articles in international journals, which greatly promoted the research progress in this field. Sadly, in 2014, Sam passed away, but his lifespan has been extended from 13 years old to 17 years old. Photo of Sam with his parents. Source: It has been 8 years since Sam died. Where has the research on HGPS progressed? Is it still possible to cure? Why does HGPS occur and is it treatable? HGPS refers to an extremely rare congenital disease that causes premature aging of the body, and can involve the skin, fat, cardiovascular, bone and other multiple organ systems. Most of the patients show a certain aging phenomenon in childhood, and the typical symptoms are growth retardation, lipoatrophy, hair loss, short stature, etc. [1]. As the disease progresses, patients can die from severe complications such as myocardial infarction, stroke, arteriosclerosis with multiple ischemic infarction, cerebral atrophy, and angiomyelopathy or severe malnutrition [2]. The disease was first proposed by Hutchinson in 1886, described again by Gilford in 1904, and later named Hutchinson-Gilford progeria syndrome [3]. Because this disease is extremely rare and rarely reported in the world, most medical institutions have insufficient knowledge of this disease, and it is easy to be misdiagnosed and missed. Children are often treated for reasons such as growth retardation and skin lesions (mainly manifested as growth retardation, alopecia, subcutaneous fat loss, and lipodystrophy). Childhood progeria is an autosomal dominant genetic disease with complex pathogenesis. The discovery of its causative gene benefited from the unremitting efforts of Leslie's team. To find the causative gene for HGPS, Leslie and his family raised big money and established the Progeria Research Foundation (PRF), with the help of doctors and geneticists. Only 3 years after the establishment of PRF, the results were published in the journal Nature on May 15, 2003, and the molecular pathogenesis of classic HGPS was proposed [4]. Studies have shown that in children with progeria in children, a point mutation (GGC-GGT) in exon 11 of the gene encoding nuclear lamin (LMNA gene) forms a new splice site, making the carboxyl group of the prelamin A peptide chain. The terminal 50 amino acid residues are excised, resulting in presenilin [3]. Presenilin is produced in many cells in children and gradually accumulates with age, leading to a series of cellular defects, including loss of heterochromatin, reduced DNA damage repair, and telomerase dysfunction. How are HGPS patients treated? The stories of Leslie and Sam have increased the attention of scientists and pharmaceutical companies to HGPS. With the development of biological technology in recent years, the treatment of HGPS has ushered in a great change from nothing. The current clinical treatments for progeria [5] include: ▌Drug therapy 1. Lonafanib: In 2020, the U.S. Food and Drug Administration (FDA) approved the listing of lonafranil for the treatment of progeria and related syndromes . Lonafanib is an orally active farnesyltransferase inhibitor that blocks the production of some presenilin proteins, thereby reducing the accumulation of these proteins in the cells of sick children and prolonging their lives. A clinical trial of 62 children who received the drug showed that lonafranib extended the average lifespan of affected children by approximately 30% during the first 3 years of treatment, compared with data from another 81 children who were not on the drug. 3 months, while sick children who were treated for up to 11 years lived an average of about 2.5 years longer. 2. Everolimus: an mTOR inhibitor, which can also help activate the autophagy signaling pathway to degrade intracellular progeria proteins. 3. Other drugs: exogenous telomerase reverse transcriptase/human telomerase catalytic subunit; oltipraz (NRF2 agonist); low-dose aspirin helps delay heart attacks and strokes. ▌Stem Cells and Gene Therapy Currently, there are two main research directions in gene therapy, namely, by extracting and inducing iPSCs from HGPS patients, and correcting their LMNA mutation by homologous recombination; by inhibiting or removing the mutation site by gene therapy. Summary: HGPS is a very rare and fatal chromosomal genetic disease. Most of the current treatments cannot completely prevent the progression of the disease and are not safe. But as more and more researchers pay attention to the disease, new research is also in full swing. The stories of Leslie and Sam are touching, and we hope that every child can grow up happily in the sun, and that every mother of a child with HGPS will no longer be sad. References: [1] Yu Jia, Yang Wenli, Yan Jie, et al. Analysis of six cases of Hutchinson-Gilford progeria in children. Chinese Journal of Endocrinology and Metabolism, 2020, 36(01):25-30.DOI:10.3760/cma.j. issn.1000-6699.2020.01.003[2] Zhao Xiaoni, Yang Fan, Ma Hui, et al. Evaluation of left ventricular systolic function in children with progeria by three-dimensional echocardiography [J]. Chinese Journal of Ultrasound Imaging, 2016,25(11):921 -925. [3] Yu Qinmei, Wang Jingjing, Ma Xiaohui, et al. Report and literature review of stroke in children with progeria [J]. China Clinical Case Results Database, 2022,04(01):E01382-E01382.[ 4] Eriksson M, Brown WT, Gordon LB, et al. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature. 2003 May 15;423(6937):293-8.[5]Xia Wei, Wang Fang, Zhou Guowei, et al. Research progress of lamin and Hutchinson-Gilford progeria. Chinese Journal of Gerontology, 2019, 38(3):336-340.DOI:10.3760/cma.j.issn.0254- 9026.2019.03.027 Source of this article: Rare Disease Channel in the medical community Author of this article: Ansheng Qile Responsible editor: Xiang Yu All the pediatric clinical knowledge doctor station apps you want to see 👇 1. Scan the QR code below the code 2. Click "Download Now" "Download the Doctor Station App and subscribe anytime, anywhere~- End - The medical community strives to be accurate and reliable in its published content when it is approved, but it does not care about the timeliness of the published content, and the accuracy and accuracy of the cited materials (if any). Completeness, etc., make any promises and guarantees, and do not assume any responsibility for the outdated content, possible inaccuracy or incompleteness of the cited materials. Relevant parties are requested to check separately when adopting or using it as a basis for decision-making.
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