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cruizin
Member
Username: Cruizin
Post Number: 27
Registered: 09-2010
| | Posted on Wednesday, January 05, 2011 - 03:01 pm: | 
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I'll just re-post this news story. It seems like a pretty important discovery to me! ... a drug that reduces proteinuria, which is a strong independent risk factor in progressively worsening kidney function ...
Original story at http://blog.al.com/spotnews/2010/12/big_step_to_understanding_kidn.html
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A UAB researcher has made a potentially major breakthrough in understanding and treating kidney disease that is associated with protein in the urine.
If it works in humans like it does in experimental rats, it could be a new treatment for kidney disease in children, which hasn't seen therapeutic progress for decades.
Preliminary experiments also suggest that Dr. Sumant Singh Chugh's findings may help diabetes patients who develop kidney problems. Those problems can affect about 20 percent to 30 percent of people with diabetes.
Chugh said he felt ecstatic when his group found they could treat the disease in rats that were genetically engineered to model the human disease.
"It's a thrill that you're doing something that potentially is going to be useful to patients in the future," he said. "I'm a physician-scientist. It's my job and mission to develop new therapies for kidney disease."
Chugh's research paper -- just published in the journal Nature Medicine -- is full of complex molecular biology and biochemistry.
A form of kidney disease in children, "minimal change disease," was discovered about 90 years ago. Children with the disease had excess protein in their urine, a sign that the kidneys were failing to filter waste products from the blood.
Electron microscopy revealed that one type cell in the kidney, the podocyte, was altered in structure. Normally they have offshoots that make them look something like spiders, Chugh said, but in people with the disease they were flattened.
What Chugh and his colleagues have done is model the kidney disease in genetically altered rats, where they found that the rat podocyte cells overproduced a protein that bears the strange name "angiopoietin-like-4."
Through genetic and biochemical studies, they found two more things. First, the gene for the angiopoietin-like-4 protein had been highly "up-regulated," making it speed production of the protein. Second, the protein now appeared to lack sialic acid, which usually is attached after the normal protein is made.
The research team thought that the angiopoietin-like-4 protein might lack sialic acid because the cell was unable to make the acid fast enough.
So they tried two simple but astonishing experiments.
Synthesis of sialic acid goes through a number of enzymatic steps as glucose is gradually converted to sialic acid. One of the intermediate precursor compounds in this multi-step synthesis is "N-acetyl-D-mannosamine."
Chugh's group first added N-acetyl-D-mannosamine to cell cultures that overproduced the protein that lacked sialic acid. The idea was that if the cells were fed enough of that precursor, sialic acid production could be boosted.
"Lo and behold, the protein now had sialic acid attached to it," Chugh said.
But would this work in actual animals?
To test that, researchers added the precursor to the drinking water of the rats and collected their urine over a 12-day period.
The result was lo and behold again. Rats fed the precursor had a 41 percent reduction in the amount of protein in their urine, a sign that the precursor was reversing symptoms of the kidney disease.
"We were ecstatic," Chugh said, saying that the change seen in rats is clinically relevant for human disease.
The research group now plans to look at the dose-response curves in rats given different amounts of the precursor, and then look into possible human clinical trials.
Chugh said he is gladdened by these findings after spending 5½ years in medical school in India, and many more years in two residencies and a fellowship.
"You feel happy that something good has come out of it," he said.
Awaiting KTX
Dx 1995 - believed to be chronic glomerulonephritis
Started CAPD Oct 2008 |
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Hostess Rise'
Board Administrator
Username: Rise
Post Number: 15381
Registered: 05-2003
| | Posted on Wednesday, January 05, 2011 - 08:04 pm: |
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Thank you Cruzin
Great promising news!
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