Research
Accidental Fungus Leads to Promising Cancer Drug
By Maggie Fox, Reuters 30/6/08
Jul 1, 2008 - 9:32:50 AM

The drug, called lodamin, was improved in one of the last experiments overseen by Dr. Judah Folkman, a cancer researcher who died in January.  Folkman pioneered the idea of angiogenesis therapy -- starving tumors by preventing them from growing blood supplies.

Lodamin is an angiogenesis inhibitor that Folkman's team has been working to perfect for 20 years. Writing in the journal Nature Biotechnology, his colleagues say they developed a formulation that works as a pill, without side-effects.

They have licensed it to SynDevRx, Inc, a privately-held Cambridge, Massachusetts biotechnology company that has recruited several prominent cancer experts to its board.  Tests in mice showed it worked against a range of tumors, including breast cancer, neuroblastoma, ovarian cancer, prostate cancer, brain tumors known as glioblastomas and uterine tumors.

It helped stop so-called primary tumors and also prevented their spread, Ofra Benny of Children's Hospital Boston and Harvard Medical School and colleagues reported.  "Using the oral route of administration, it first reaches the liver, making it especially efficient in preventing the development of liver metastasis in mice," they wrote in their report.  "Liver metastasis is very common in many tumor types and is often associated with a poor prognosis and survival rate," they added.

'ALMOST CLEAN' LIVERS

"When I looked at the livers of the mice, the treated group was almost clean," Benny said in a statement. "In the control group you couldn't recognize the livers -- they were a mass of tumors."

The drug was known experimentally as TNP-470, and was originally isolated from a fungus called Aspergillus fumigatus fresenius.

Harvards's Donald Ingber discovered the fungus by accident while trying to grow endothelial cells -- the cells that line blood vessels.  The mold affected the cells in a way known to prevent the growth of tiny blood vessels known as capillaries.

Ingber and Folkman developed TNP-470 with the help of Takeda Chemical Industries in Japan in 1990.

But the drug affected the brain, causing depression, dizziness and other side-effects.  It also did not stay in the body long and required constant infusions.  The lab dropped it.

Efforts to improve it did not work well.  Then Benny and colleagues tried nanotechnology, attaching two "pom-pom"-shaped polymers to TNP-470, protecting it from stomach acid.

In mice, the altered drug, now named lodamin, went straight to tumor cells and helped suppress melanoma and lung cancer, with no apparent side effects, Benny said.

All untreated mice had fluid in the abdominal cavity, and enlarged livers covered with tumors.  Mice treated with lodamin had normal-looking livers and spleens, the researchers said.

Twenty days after being injected with cancer cells, four out of seven untreated mice had died, while all treated mice were still alive, Benny's team reported.

"I had never expected such a strong effect on these aggressive tumor models," she said.  The researchers believe lodamin may also be useful in other diseases marked by abnormal blood vessel growth, such as age-related macular degeneration.