August 8, 2012

Quest for a wonder drug started with shrew bait

By DAKSHANA BASCARAMURTY

Facing long odds on bringing it to market, a Canadian entrepreneur is about to start human trials for a drug derived from the saliva of the mouse-sized mammal. He believes it can treat three kinds of cancer

First, he lured shrews into his backyard with No Name-brand pepperoni. Then, he extracted their venom-laced saliva.

Now Jack Stewart, a Sackville, N.B.-based biochemist-turned-biotechnology entrepreneur, is about to start a human trial for a drug developed from a compound found in shrew spit that could treat ovarian, breast and prostate cancers without many of the side effects of chemotherapy.

It's an unusual discovery – others knew the saliva had paralytic properties and Dr. Stewart had originally hoped to develop a pain medication. But when he studied the compound in the spit more closely, he found potential cancer-fighting qualities.

Like all new drugs bearing the weight of great expectations, Dr. Stewart's shrew-saliva spinoff faces long odds. Health Canada and the U.S. Food and Drug Administration (FDA) set a high bar for approval. The cost of executing clinical trials can be prohibitive, and even if a medicine does reach the market, the competition from other drugs is fierce.

"Starting from a drug conceptually that's entering preclinical testing in an animal model and following that through to a licensed drug, the fall-off is considerable," said Ralph Meyer, director of the National Cancer Institute of Canada's clinical trials groups.

But the novelty of the source of the drug – called soricidin, the compound found in the shrew saliva – and the fact that it could treat three types of cancers has been enough to take Dr. Stewart to this stage. In a few weeks, his company, Soricimed Biopharma Inc., plans to start its first clinical trial on patients in the United States and Canada. There are three phases of human trials, each more rigorous – and expensive – than the last.

Dr. Stewart hopes the trial will prove his drug is a viable alternative to chemotherapy. Unlike chemo, which takes a carpet-bombing approach and kills healthy cells along with cancerous ones, soricidin works in a slower, less destructive way, he said.

Ovarian, breast and prostate cancers produce high numbers of a certain type of calcium channel that feed calcium to cancer cells and allows them to proliferate. The soricidin works to plug the calcium pipeline, which eventually leads to death of the cancer cells.

"It's a resetting of the cancer cell rather than a poisoning of it," Dr. Stewart explained. "We leave it to the cancer cell to kill itself."

Simply getting the soricidin was a challenge, Dr. Stewart said. He tried everything from peanut butter to seeds to trap shrews in his backyard, all of which failed. One morning, though, his traps were filled with the critters. It turns out discount pepperoni brings all the shrews to the yard.

Since Dr. Stewart said there are "not enough shrews on the planet" to produce sufficient soricidin for his trials, his team developed a synthetic, which was used during animal testing and will soon be administered in human trials.

While Soricimed celebrates reaching the human-trial stage, it has many obstacles to clear before its drug can reach the market.

From 2004 to 2011, only 6.7 per cent of the oncology drugs that made it to the first phase of clinical trial were eventually approved by the FDA for sale, according to data tracked by the Biotechnology Industry Organization, a Washington-based trade association. For all other drugs, the approval rate was nearly double.

"It's difficult to structure and run [oncology drug] trials with clear, robust criteria for success," said Veronika Litinski, a senior adviser in life sciences and health-care practice at the MaRS Centre in Toronto.

With HIV drugs, she says, researchers look at the viral load before and after the drug is administered – the results are easily measurable. Whereas in cancer drug testing, they rely on survival rates. Did the drug extend the life of a patient by a few months? A year? What was the quality of life for the patient during that year? Did the side effects offset the benefits?

Even if its first trial is a success, Soricimed will need to round up cash to proceed with more trials since it has only raised $11-million so far through private investors and federal government programs.

The anticipated cost of the first human trial is $2.5-million, said Paul Gunn, Soricimed's chief executive officer. For phase 2, the company will have to shell out anywhere between $4-million and $40-million. The third trial could come with a price tag of more than $100-million.

The small company hopes to partner with a larger pharmaceutical or biotech company after phase 1, Mr. Gunn said.

Even if soricidin were approved by Health Canada or the FDA, it would still face an array of challenges. The way a drug is marketed, the competition it faces and the willingness of provincial health authorities to fund it all play into how well a new medicine does.

"[Soricimed] has cleared a lot of hurdles to get to phase 1," Dr. Meyer said, "but they still have a lot to get through."

From Wikipedia:

Shrews are unusual among mammals in a number of respects. Unlike most mammals, some species of shrew are venomous. Shrew venom is not conducted into the wound by fangs, but by grooves in the teeth. The venom contains various compounds, and the contents of the venom glands of the American short-tailed shrew are sufficient to kill 200 mice by intravenous injection. One chemical extracted from shrew venom may be potentially useful in the treatment of blood pressure while another compound may be useful in the treatment of some neuromuscular diseases and migraines.^[6] The saliva of the Northern Short-tailed Shrew (Blarina brevicauda) contains the peptide soricidin and has accordingly been studied for use in treating ovarian cancer.^[7] Also, along with the bats and toothed whales, some species of shrew use echolocation. Unlike most other mammals, shrews lack a zygomatic bone (also called the jugal), and therefore have an incomplete zygomatic arch.

Shrews hold nearly 10% of their mass in their brain, which is the highest brain to body mass ratio of all animals (including humans).^{[citation needed]}