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Local Start-Up Looking to Break Blood-Brain Barrier

Local Start-Up Looking to Break Blood-Brain Barrier

Biotech: VC Firm Funding Imagine Pharmaceuticals, But Key Drug Is Years Off


A world-renowned neurosurgeon and San Diego-based venture capital firm Forward Ventures believe their investment in a local start-up company may hold the key to breaching the blood-brain barrier that prevents the delivery of drugs into tumors.

Dr. Keith Black, director of neurosurgery at Cedars Sinai Medical Center in Los Angeles, is the scientific brain behind San Diego-based start-up Imagine Pharmaceuticals Inc.

So far, Imagine is a one-man show. Its president and chief executive, Dr. James Merritt, shares office space at Forward Ventures in the University Towne Centre area. Black, who is Imagine’s chief scientific adviser, directs a research team in Los Angeles.

“It’s been estimated that 98 percent of drugs for brain tumors cannot reach the brain effectively,” said Black.

The blood-brain barrier, a network of special capillaries is helpful, because it protects the brain from dangerous toxins and bacteria.

For brain cancer patients, however, that barrier becomes a hazard by blocking entry of helpful medicines into the tumor.

Black thinks he has found a way around it.

He discovered a molecular difference between the capillaries in tumors and healthy parts of the brain.

Based on that finding, Black created a molecule that opens up the barrier for a limited amount of time, but long enough for potent chemotherapy drugs to pass through, attach to the tumor and destroy it, while leaving the healthy tissue intact.

“We can keep the window open for about 60 minutes,” Black said. “The advantage with our class of drug is that it does not open the normal blood brain barrier, but only opens the abnormal blood brain barrier into the diseased tissue so we don’t increase the toxicity of a drug by exposing it into the normal brain.”

Early studies on tumor cells in the laboratory suggest Black’s treatment improves the delivery of chemotherapy drugs into the brain three- to twelve-fold.

In rats, the molecule opened the window long enough for various drugs to hit the tumor.

The results suggested rats treated with Black’s molecule and chemotherapy lived 88 percent longer compared to rats receiving chemotherapy alone. Animals lived for 90 days after receiving the combined therapy.

Rats on chemotherapy survived for 55 days. But it’s a long way from testing on rats to humans.

Imagine has many years of testing in order to prove that its molecule is safe and effective in cancer patients. It can take up to a dozen years before a drug makes it to the marketplace.

So far, Black has won the financial backing of three venture capital groups.

In June 2003, Forward Ventures together with Domain Associates LLC of Princeton, N.J., and RCT Bioventures West of San Francisco raised $3.7 million in a first round of financing.

Black said additional funding is contingent on whether he succeeds testing the drug in humans.

Merritt said there’s no question the molecule addresses a clinical need in oncology: “Namely the treatment and hopefully prevention of spread of cancer into the brain, which is a common and usually fatal complication of both childhood and adult cancers.”

Sixty percent of lung cancer patients and 30 percent of breast cancer patients are at risk for the complication, Black said.

“And once the tumor goes into the brain it cannot be treated with chemotherapy,” he added.

Current treatment of whole brain radiation can help extend lives. But it is not for all patients.

Meritt, who was lured from Introgen Therapeutics Inc. in Houston to head Imagine a year ago, hopes the Food and Drug Administration will give the green light for human studies this year.

Patients receive the experimental drug with chemotherapy intravenously.

The soonest the drug may hit the marketplace is 2010, but Merritt cautioned many unknowns remain.


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