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Human Organoids Show Drug Activity in Lab Animals

Goldfinch on wire cage

Goldfinch (A. Kotok)

7 July 2022. A study shows implanted lab-grown pieces of human 3-D kidney tissue can demonstrate chemical activity of drugs in preclinical tests with lab rats. Findings from the study conducted by Goldfinch Bio Inc., a biotechnology company in Cambridge, Massachusetts, appear in yesterday’s issue of the journal Science Advances.

Goldfinch Bio discovers and develops precision treatments for kidney diseases. Chronic kidney disease affects an estimated 850 million people worldwide, leading to progressive loss of kidney function and end-stage kidney disease that requires either dialysis or a kidney transplant. Goldfinch says few, if any, treatments are available to alter the course of the disease.

The company’s process focuses on subsets of chronic kidney disease associated with addressable molecular indicators or biomarkers. Goldfinch’s lead therapy candidate, code-named GFB-887, is a treatment for a type of focal segmental glomerulosclerosis or FSGS, where scar tissue develops on glomeruli, the parts of the kidney that filter waste from blood. GFB-887 is a small-molecule drug that seeks to limit mutated transient receptor potential canonical 5 or TRPC5 proteins associated with FSGS. GFB-887 is now being assessed in a mid-stage clinical trial.

Native kidneys not translatable

Goldfinch Bio’s discovery technology mines databases of some 20,000 individuals with and without kidney disease, using algorithms to identify molecular and environmental targets associated the disease. A key part of the company’s discovery process is validation of therapy targets with organoids, pieces of human kidney tissue grown in the lab from stem cells. Goldfinch says organoids are needed to show interactions of drug candidates with human kidney tissue, both in the lab cultures and animals. Kidneys of lab mice or rats, say the paper’s authors, are not considered translatable to humans, thus the need to transplant human kidney tissue organoids into the animals.

Science and Enterprise reported in Feb. 2019 on research by a team at Harvard University to grow kidney organoids with blood vessels, with one of the researchers, Joseph Bonventre, a scientific founder of Goldfinch Bio. The new study implanted human kidney organoids in lab rats with limited immune systems. The organoids were made from induced pluripotent stem cells, or adult stem cells, and cultured in the lab for two to four weeks. The kidney tissue included injuries to podocytes, cells on blood vessel surfaces in glomeruli similar to FSGS.

A key question of the study is the ability of blood vessels in kidney organoids to circulate drugs, in this case GFB-887, throughout the transplanted tissue. The findings show GFB-887 distributed throughout and accumulated in the kidney to a greater extent than found in the rats’ blood plasma. Results also show podocytes in the organoids were protected by GFB-887, with TRPC5 channels in the rats limited by the drug. Inhibited TRPC5 channels were also found in the rats own kidneys.

Goldfinch Bio believes transplanted human organoid tissue can be extended to test drugs in other organs. “We believe our pioneering approach is applicable across an array of tissues and organs,” says Goldfinch CEO Anthony Johnson in a company statement, “and we look forward to sharing our findings with the broader drug development community in hopes of ushering in a new era of more translatable preclinical models and, ultimately, more efficient drug discovery.”

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