A new study is in the works, and it will investigate how cystinosis, a genetic disorder characterized by an accumulation of the amino acid cystine in the cells, leads to male infertility. Titled “Perturbations in the V-ATPase Pathway Drive Pathology in the Male Reproductive System in Cystinosis,” this study will be funded by both the Cystinosis Research Network and Cystinosis Ireland.
Cystinosis is a rare, inherited disorder that is characterized by the accumulation and crystalization of the amino acid cystine. After time, this buildup can lead to kidney failure and organ damage. There are three forms of this condition: nephropathic, intermediate, and ocular (non-nephropathic). The first of the three manifests during infancy and causes nutrients to be lost through the urine, rickets, excessive thirst, and corneal crystals. The second is very similar, except the onset of symptoms is later in life. Lastly, ocular cystinosis tends to lack some of the more severe symptoms and just causes corneal crystals.
The CTNS gene is mutated in those with cystinosis, and it is passed down in an autosomal recessive pattern. This mutation disrupts the normal functions of cystine by lowering the amount of cystinosin, which is the protein needed to transport cystine. The amino acid then accumulates and causes the characteristic symptoms. Effects on the kidneys tend to be the major symptoms; kidney failure is not uncommon in those with nephropathic or intermediate cystinosis. Other body parts are impacted as well, such as the muscles, central nervous system, liver, thyroid, and white blood cells. Corneal crystals can lead to a sensitivity to light and even blindness as well. Some affected males experience infertility.
Both Cystinosis Ireland and the Cystinosis Research Network have pledged €150,000 over three years to fund a study into the molecular and cellular causes behind infertility in males with cystinosis. The goal of the research is to discover a treatment that will allow these affected individuals to have children. Additionally, it will provide a better understanding of the rare condition, which aids future research.
This study follows two similar previous projects:
- “Targeting Autophagy in Nephropathic Cystinosis,” led by Professor Minnie Sarwal at the University of California, San Francisco
- “Unravelling the mechanisms of azoospermia and potential future treatments in male cystinosis patients,” led by Professor Elena Levtchenko in UZ Leuven, Belgium
This is not the first time that the two organizations have worked together; their goals have aligned twice in the past. Most recently, they funded a research project that intended to utilize genetic editing to create “cystinotic cell lines from the male testes.” Not only will these cell lines be important for the research discussed in this article, but they will influence all future cystinosis research.
Both Cystinosis Ireland and the Cystinosis Research Network hope that this collaboration is successful and that they may work together in the future to enable more progress in cystinosis research.
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