From Science Daily
Cancer drug may benefit patients with inherited form of kidney disease
A cancer drug called bosutinib may inhibit the growth of cysts in patients with autosomal dominant polycystic kidney disease (ADPKD), according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings point to a potential new treatment strategy for affected patients, but the long-term benefits remain to be determined.
ADPKD is an inherited disorder that affects up to 1 in 1000 people and is characterized by cysts in the kidney and other organs. As patients' kidney volume increases due to cyst growth, they gradually lose their kidney function and often develop kidney failure. Current treatments are primarily supportive, such as focusing on hypertension and other secondary complications.
The inherited mutations that cause ADPKD affect a protein involved in various signaling pathways that often involve enzymes called tyrosine kinases. Therefore, a team led by Vladimir Tesar, MD, PhD (Charles University and General University Hospital, in the Czech Republic) tested the potential of an investigational drug called bosutinib that inhibits a particular tyrosine kinase called Src/Bcr-Abl.
The phase 2 study included patients with ADPKD who were randomized 1:1:1 to bosutinib 200 mg/day, bosutinib 400 mg/day, or placebo. Of 172 patients enrolled, 169 received at least one treatment. The higher dose of bosutinib was not well tolerated.
The annual rate of kidney enlargement was reduced by 66% for patients receiving bosutinib 200 mg/day vs. those receiving placebo (1.63% vs. 4.74%, respectively) and by 82% for all patients receiving bosutinib vs. those receiving placebo (0.84% vs. 4.74%, respectively). The study was not powered to demonstrate a treatment effect on kidney function, but there was no evidence of a benefit associated with bosutinib compared with placebo over the 2-year treatment period.
"The reduction in growth of cysts through treatment with bosutinib was confirmed, although gastrointestinal side effects (primarily diarrhea), which were partly dose-dependent, may represent a substantial drawback for the further development of the drug for patients with ADPKD," said Prof. Tesar.
Last week in Nature, an article by David Cyranoski was published regarding the rise of preimplantation genetic diagnosis (PGD) in Chinese fertility clinics with the intention of eradicating genetic diseases.
PGD was first performed in England almost 2 decades ago to preferentially select for female embryos to be implanted in parents at risk for X-linked genetic conditions. Since then, the technique has advanced significantly; while many countries are performing PGD, the article in Nature indicates that China is outperforming all other countries, and furthermore, PGD is not considered to be part of an ethical issue there as it is in other countries.
Using PGD, Chinese clinics have reported being able to avoid producing children with, or at risk for, retinoblastoma, short-rib-polydactyly syndrome, Brittle-bone disease, Huntington’s disease, polycystic kidney disease and deafness.
The eradication of a genetic, chronic condition could have a significant impact on healthcare costs. For example, the cost for a PGD to avoid having a child with cystic fibrosis would be $57,000. While seemingly expensive, a cystic fibrosis patient incurs about $2.3 million in medical costs over his or her lifetime.
Similarly to the way that Iceland’s eradication of Down syndrome has led to concerned tweets like the one below, similar concerns could be justified.
Specifically, PGD raises concerns that it will be used only by the well-off to create an elite genetic class. It is an expensive procedure, likely to be limited to families with better healthcare coverage.
In China, while many parents are concerned about genetic diseases, some parents are trying to weed out genetic anomalies to create a superior child. Sijia Lu, chief technology officer of Yikon Genomics has stated some couples are asking to weed out the mutation that renders many Asians unable to process alcohol. Right now, such selection is not allowed.
While such queries are theoretically a concern, some argue that it shouldn’t be. Joe Leigh Simpson, a medical geneticist at Florida International University in Miami said, “With every reproductive-biology advance, we get the same questions: ‘won’t there be a slippery slope that leads to abuse?’ But it never happens.”
As for using PGD for its intended use – to screen for genetic diseases – its use in the United States remains limited right now, partly because is very expensive and insurance generally does not cover it.
PGD was first performed in England almost 2 decades ago to preferentially select for female embryos to be implanted in parents at risk for X-linked genetic conditions. Since then, the technique has advanced significantly; while many countries are performing PGD, the article in Nature indicates that China is outperforming all other countries, and furthermore, PGD is not considered to be part of an ethical issue there as it is in other countries.
Using PGD, Chinese clinics have reported being able to avoid producing children with, or at risk for, retinoblastoma, short-rib-polydactyly syndrome, Brittle-bone disease, Huntington’s disease, polycystic kidney disease and deafness.
The eradication of a genetic, chronic condition could have a significant impact on healthcare costs. For example, the cost for a PGD to avoid having a child with cystic fibrosis would be $57,000. While seemingly expensive, a cystic fibrosis patient incurs about $2.3 million in medical costs over his or her lifetime.
Similarly to the way that Iceland’s eradication of Down syndrome has led to concerned tweets like the one below, similar concerns could be justified.
Iceland isn't actually eliminating Down Syndrome. They're just killing everybody that has it. Big difference. #Downsyndrome#abortion twitter.com/CBSNews/status…
Specifically, PGD raises concerns that it will be used only by the well-off to create an elite genetic class. It is an expensive procedure, likely to be limited to families with better healthcare coverage.
In China, while many parents are concerned about genetic diseases, some parents are trying to weed out genetic anomalies to create a superior child. Sijia Lu, chief technology officer of Yikon Genomics has stated some couples are asking to weed out the mutation that renders many Asians unable to process alcohol. Right now, such selection is not allowed.
While such queries are theoretically a concern, some argue that it shouldn’t be. Joe Leigh Simpson, a medical geneticist at Florida International University in Miami said, “With every reproductive-biology advance, we get the same questions: ‘won’t there be a slippery slope that leads to abuse?’ But it never happens.”
As for using PGD for its intended use – to screen for genetic diseases – its use in the United States remains limited right now, partly because is very expensive and insurance generally does not cover it.
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