kebaldwin
Mon, Oct-10-05, 13:30
Zeroing In On Inflammation
Kerry Dolan, 10.10.05, 9:00 AM ET
The discovery of a gene linked to inflammation reinforces the science that shows a genetic link to diseases such as diabetes and obesity. Yesterday, a group of researchers in the U.S. and Australia announced it had discovered a human gene that regulates inflammation--the first gene of its kind. The discovery has implications for a wide range of diseases, including cancer, cardiovascular disease, diabetes, obesity and Alzheimer's, because inflammation is understood to play a critical role in all of them.
The findings, published in the Oct. 9 online edition of Nature Genetics, were funded by ChemGenex Pharmaceuticals (nasdaq: CXSP - news - people ), a biotech firm with operations in Menlo Park, Calif. and Geelong, Australia. ChemGenex initially identified the gene in the desert sand rat, a species that, like humans, has certain individuals with a greater propensity than others for obesity and diabetes, as well as the inflammation associated with those conditions.
In their native environment, the desert around the Red Sea, the sand rats scrounge for food mainly at night. But when put in captivity with free access to food, about half the sand rats became obese. Half of those became diabetic, and half of the diabetic population became severely diabetic--proportions that mirror those in the human population, says Greg Collier, chief executive of ChemGenex. The ChemGenex scientists believed there was a genetic explanation for why only some sand rats became obese or diabetic, and determined that the affected sand rats exhibited a different pattern of a previously undiscovered gene, now called SEPS1 (Selenoprotein S).
A consortium of scientists led by John Blangero at the Southwest Foundation for Biomedical Research in San Antonio identified the SEPS1 gene's influence on inflammation in humans. They found that SEPS1 is a type of "garbage truck" that helps clear cells of misfolded, or abnormally shaped, proteins that build up when cells are placed under stress. Inflammation develops when the faulty proteins accumulate in a cell. People with a genetic variation that impairs SEPS1's ability to purify the cells by clearing out the bad proteins tend to suffer higher levels of inflammation. The study found the same relationship between SEPS1 and inflammation in two geographically and ethnically distinct populations--one in Wisconsin and the other in Texas.
"If you're a person that carries this variation in the gene, you're going to have a much enhanced inflammatory response to stress on the cells," says ChemGenex's Collier.
ChemGenex and scientists from the Southwest Foundation for Biomedical Research are beginning to study how the SEPS1 gene influences a variety of diseases, including cardiovascular disease, diabetes, obesity, preeclampsia and some infectious diseases. Collier hopes to come up with a drug that will inhibit inflammation by potentially regulating the SEPS1 gene. ChemGenex owns all the intellectual property and the commercial rights for the newly discovered gene.
The research team also included scientists from the Medical College of Wisconsin, Deakin University in Geelong, Australia, and the International Diabetes Institute in Melbourne, Australia.
ChemGenex has two cancer drugs in midstage clinical trials. One of the drugs, ceflatonin, is for patients with chronic myeloid leukemia (CML), a rare cancer of the blood that is currently being treated with Gleevec, a drug made by Novartis (nyse: NVS - news - people ).
Gleevec achieved sales of $1.6 billion last year, largely for off-label use, according to a report by analyst Matthijs Smith of Australian stockbroker Petersons. But roughly 20% of patients with CML develop resistance to Gleevec, and another 20% to 30% of patients do not respond at all. Smith figures a second line therapy for CML could generate as much as $250 million in sales, and possibly more for off-label use.
Like many small biotech companies, ChemGenex loses money. The company, which is publicly traded in Australia, listed its shares on Nasdaq in June this year and has a market capitalization of approximately $50 million.
http://www.forbes.com/2005/10/10/genetics-chemgenex-inflammation-cz_kd_1010chemgenex_print.html
Kerry Dolan, 10.10.05, 9:00 AM ET
The discovery of a gene linked to inflammation reinforces the science that shows a genetic link to diseases such as diabetes and obesity. Yesterday, a group of researchers in the U.S. and Australia announced it had discovered a human gene that regulates inflammation--the first gene of its kind. The discovery has implications for a wide range of diseases, including cancer, cardiovascular disease, diabetes, obesity and Alzheimer's, because inflammation is understood to play a critical role in all of them.
The findings, published in the Oct. 9 online edition of Nature Genetics, were funded by ChemGenex Pharmaceuticals (nasdaq: CXSP - news - people ), a biotech firm with operations in Menlo Park, Calif. and Geelong, Australia. ChemGenex initially identified the gene in the desert sand rat, a species that, like humans, has certain individuals with a greater propensity than others for obesity and diabetes, as well as the inflammation associated with those conditions.
In their native environment, the desert around the Red Sea, the sand rats scrounge for food mainly at night. But when put in captivity with free access to food, about half the sand rats became obese. Half of those became diabetic, and half of the diabetic population became severely diabetic--proportions that mirror those in the human population, says Greg Collier, chief executive of ChemGenex. The ChemGenex scientists believed there was a genetic explanation for why only some sand rats became obese or diabetic, and determined that the affected sand rats exhibited a different pattern of a previously undiscovered gene, now called SEPS1 (Selenoprotein S).
A consortium of scientists led by John Blangero at the Southwest Foundation for Biomedical Research in San Antonio identified the SEPS1 gene's influence on inflammation in humans. They found that SEPS1 is a type of "garbage truck" that helps clear cells of misfolded, or abnormally shaped, proteins that build up when cells are placed under stress. Inflammation develops when the faulty proteins accumulate in a cell. People with a genetic variation that impairs SEPS1's ability to purify the cells by clearing out the bad proteins tend to suffer higher levels of inflammation. The study found the same relationship between SEPS1 and inflammation in two geographically and ethnically distinct populations--one in Wisconsin and the other in Texas.
"If you're a person that carries this variation in the gene, you're going to have a much enhanced inflammatory response to stress on the cells," says ChemGenex's Collier.
ChemGenex and scientists from the Southwest Foundation for Biomedical Research are beginning to study how the SEPS1 gene influences a variety of diseases, including cardiovascular disease, diabetes, obesity, preeclampsia and some infectious diseases. Collier hopes to come up with a drug that will inhibit inflammation by potentially regulating the SEPS1 gene. ChemGenex owns all the intellectual property and the commercial rights for the newly discovered gene.
The research team also included scientists from the Medical College of Wisconsin, Deakin University in Geelong, Australia, and the International Diabetes Institute in Melbourne, Australia.
ChemGenex has two cancer drugs in midstage clinical trials. One of the drugs, ceflatonin, is for patients with chronic myeloid leukemia (CML), a rare cancer of the blood that is currently being treated with Gleevec, a drug made by Novartis (nyse: NVS - news - people ).
Gleevec achieved sales of $1.6 billion last year, largely for off-label use, according to a report by analyst Matthijs Smith of Australian stockbroker Petersons. But roughly 20% of patients with CML develop resistance to Gleevec, and another 20% to 30% of patients do not respond at all. Smith figures a second line therapy for CML could generate as much as $250 million in sales, and possibly more for off-label use.
Like many small biotech companies, ChemGenex loses money. The company, which is publicly traded in Australia, listed its shares on Nasdaq in June this year and has a market capitalization of approximately $50 million.
http://www.forbes.com/2005/10/10/genetics-chemgenex-inflammation-cz_kd_1010chemgenex_print.html