| ▲ Research results have been announced that gene therapy for hereditary kidney disease showed an effect. (Photo = DB) |
[메디컬투데이=한지혁 기자] Gene therapy for hereditary kidney disease has been shown to be effective.
The results of a study on the effect of a new gene therapy for autosomal dominant polycystic kidney disease (ADPKD) were published in the journal Nature Communications.
ADPKD is a common genetic disease that occurs in 1 in 1000 to 2500 people worldwide and is characterized by the formation of cysts in the kidneys and decreased renal function.
The most common cause of ADPKD is a mutation in the PKD-1 gene resulting in a change in the function of the polycystin 1 (PC1) protein, accounting for about 78% of all cases. Blocking the expression of the mutated PKD-1 gene can reverse pathological changes, including cysts, but the length of the PKD-1 gene is not suitable for general gene therapy.
According to previous animal and cell culture experiments, problems in the energy metabolism pathway in which mitochondria, a type of organelle, produce adenosine triphosphate (ATP), were observed in the ADPKD model.
In addition, direct intervention in the problematic metabolic pathway has been shown to help alleviate the symptoms of ADPKD. However, the mechanism mediating the association between these metabolic pathway problems and PKD-1 genetic mutations is not well known.
The PC1 protein is normally found in the cell membrane, but it is also cut into smaller pieces and transported inside the cell. In this study, the research team conducted an experiment in mice to see if ‘PC1-CTT’, a fragment of the PC1 protein that migrates to the mitochondria, could cause an abnormality in the metabolic pathway.
The researchers reported that expression of the gene encoding the PC1-CTT protein fragment slowed the growth of ADPKD kidney cysts and helped preserve kidney structure and function.
The researchers investigated the interactions between the PC1-CTT fragment and other proteins in kidney cells to identify the molecular pathways mediating the effects of the PC1-CTT fragment.
As a result, an enzyme named ‘NNT (Nicotinamide Nucleotide Transhydrogenase)’ located inside the mitochondria showed the most significant interaction. In addition, NNTs have been shown to play an important role in the maintenance of various metabolic functions, including oxidative stress relief.
No improvement in cyst and kidney structure was observed when the PC1-CTT fragment was expressed in mice that do not express NNT. This suggests that the ability of PC1-CTT to reduce the severity of ADPKD depends on its interaction with NTT.
Experts evaluated the results of this study as positive in that it gave hope for the maintenance of kidney function in ADPKD patients and showed the importance of gene therapy.
Medical Today Reporter Han Ji-hyeok (hanjh3438@mdtoday.co.kr)
[저작권자ⓒ 메디컬투데이. 무단전재-재배포 금지]
2023-06-02 06:24:49
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