Friday, 6 September 2013

Stem cell study points to new treatment for polycystic kidney disease

Polycystic kidneys
A new study by researchers at the Brigham and Women’s Hospital, the Mayo Clinic, and the Harvard Stem Cell Institute has uncovered a process that is defective in patients with autosomal dominant polycystic kidney disease, a common cause of kidney failure. The findings, published on the upcoming issue of Journal of the American Society of Nephrology, point to a new potential therapeutic approach for the disease.

Polycystic kidney disease (PKD), is the fourth leading cause of kidney failure worldwide and comes in two types: autosomal dominant polycystic kidney disease (ADPKD) develops in adulthood and is quite common, while autosomal recessive polycystic kidney disease (ARPKD) is rare but frequently fatal. The disease is caused by mutations in either of two proteins, polycystin-1 and polycystin-2, while ARPKD is caused by mutations in a protein called fibrocystin. Currently, there is no cure or widely adopted clinical therapy for either types of the disease.


Polycystin-1, polycystin-2, and fibrocystin are all found in a cell’s primary cilium, which acts as the cell’s antenna and is intimately involved in human embryonic development as well as the development of certain diseases, including PKD.

"What we don’t know, and were hoping to better understand, is what goes wrong with these proteins in the cells of PKD patients and what kinds of therapies might help those cells." said Joseph Bonventre, MD, PhD (Brigham and Women’s Hospital).

The research team, led by Dr. Bonventre, studied cells obtained from five PKD patients: three with ADPKD and two with ARPKD. The investigators then reprogrammed skin cells from the patients and turned them into induced pluripotent stem cells, which can give rise to many different cell types and tissues. When the researchers examined these cells under the microscope, they discovered that the polycystin-2 protein traveled normally to the antenna, or cilium, in cells from ARPKD patients, but it had trouble reaching the antenna in ADPKD patients. When they sequenced the DNA in these ADPKD patient cells, the investigators found mutations in the gene that encodes polycystin-1, suggesting that polycystin-1 helps shepherd polycystin-2 to the cilium.

"When we added back a healthy form of polycystin-1 to our patient cells, it traveled to the cilium and brought its partner polycystin-2 with it, suggesting a possible therapeutic approach for PKD. This was the first time induced pluripotent stem cells have been used to study human kidney disease where a defect related to disease mechanisms has been found" explained Dr. Freedman. 

The researchers noted that reprogrammed stem cells from patients with ADPKD may also be useful for testing new therapeutics before trying them out in humans.

In an accompanying editorial, Alexis Hofherr, MD and Michael Köttgen, MD (University Medical Centre, in Freiburg, Germany) stated that the study has “laid the groundwork for using induced pluripotent stem cells in PKD research. This important step forward will provide novel opportunities to model PKD pathogenesis with human cells with defined patient mutations.”

Reference
Benjamin S. Freedman, Albert Q. Lam, Jamie L. Sundsbak, Rossella Iatrino, Xuefeng Su, Sarah J. Koon, Maoqing Wu, Laurence Daheron, Peter C. Harris, Jing Zhou, and Joseph V. Bonventre. (2013). Reduced Ciliary Polycystin-2 in Induced Pluripotent Stem Cells from Polycystic Kidney Disease Patients with PKD1 Mutations Journal of the American Society of Nephrology

No comments:

Post a Comment

Please note that we dont offer any kind of medical advice. Questions requesting specific medical advice (e.g. where can I get this treatment, will this cure XXX condition, etc) will be published but most probably ignored by the administrators. :)

Note to spammers: You shall not pass. If you really want a link from us then consider making a stem cell related guest post !