New drug triggers tissue regeneration

Scientists, including one of Indian-origin, have identified an incredibly potent drug that repairs damage to the colon, liver and bone marrow in mice, an advance that may pave the way for a pill that enables growth of new tissues to replace damaged ones in humans.
Researchers at Case Western Reserve and University of Texas Southwestern Medical Center now hope to develop the drug - named "SW033291" - for use in human patients.
"We have developed a drug that acts like a vitamin for tissue stem cells, stimulating their ability to repair tissues more quickly," said Sanford Markowitz, the Ingalls Professor of Cancer Genetics at the Case Western Reserve University's School of Medicine.

"The drug heals damage in multiple tissues, which suggests to us that it may have applications in treating many diseases," Markowitz said.
The key to the drug's potential involves a molecule the body produces that is known as prostaglandin E2, or PGE2. It is well established that PGE2 supports proliferation of many types of tissue stem cells.
Previous research had demonstrated that a gene product found in all humans, 15-hydroxyprostaglandin dehydrogenase (15-PGDH), degrades and reduces the amount of PGE2 in the body.

Markowitz and colleagues hypothesised that inhibiting 15-PGDH would increase PGE2 in tissues to promote and speed tissue healing.

Yongyou Zhang, a Case Western Reserve research associate in Markowitz's lab developed a test where cells glowed when 15-PGDH levels changed.
Zhang then travelled to UT Southwestern's Harold C Simmons Comprehensive Cancer Center, and collaborated with other researchers to comb through the centre's library of 230,000 different chemicals.
Ultimately they identified one chemical that they found inactivated 15-PGDH.
"The chemical, SW033291, acts in an incredibly potent way. It can inactivate 15-PGDH when added at one part in 10 billion into a reaction mixture, which means it has promise to work as a drug," Markowitz said.
A series of experiments showed that SW033291 could inactivate 15-PGDH in a test tube and inside a cell, and, most importantly, when injected into animal models.

Markowitz then collaborated with Stanton L Gerson, director of the Case Comprehensive Cancer Center.
Case Western Reserve research associate Amar Desai, worked between the Markowitz and Gerson laboratories to determine the effect of SW033291 on mice that had received lethal doses of radiation and then received a partial bone marrow transplant.
Without SW033291, the animals died. With it, they recovered.
More detailed studies showed that mice given SW033291 recovered normal blood counts six days faster than mice that were transplanted without receiving SW033291.
When investigators treated mice with other diseases, the SW033291 drug accelerated tissue recovery.