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Neuro Innovations - When Scientific Surprises Lead to New Drugs

Collaborations in Discovery

When Scientific Surprises Lead to New Drugs

Date: November 1, 2011

John Laterra
John Laterra

A cademic researchers are great at fundamental science, and pharmaceutical companies are great at developing drugs, but sometimes the two have trouble linking up. Some Johns Hopkins neuroscience researchers are closing that gap.

One of them is Barbara Slusher, who is leading a new drug discovery initiative at the Johns Hopkins’ Brain Science Institute focused on transforming Hopkins’ basic neuroscience discoveries into useful drugs for patients. Her multidisciplinary team is a collection of 20 biologists, chemists and pharmacologists, all with significant pharmaceutical drug discovery experience. “The researchers here at Hopkins are world-renowned, but their findings aren’t always translated into real-world medicine,” says Slusher.

Slusher’s experienced team has been on campus for only 18 months, but already their results are impressive. For example, the group is working with an amino acid called D-serine that Hopkins research showed stimulates glutamate receptors in the brain, decreasing schizophrenic symptoms. Unfortunately, the body quickly breaks down D-serine, requiring dangerously large doses for efficacy. The group’s solution: designing a molecule that slows the amino acid’s breakdown, allowing the dose to be reduced by 90 percent. Now the team is developing the drug combination for a clinical trial.

Although they are a brain-science focused team, serendipity also led them to a cancer project. The group was working on a drug that blocks an enzyme called glutaminase—implicated in neurodegeneration—until new Hopkins research discovered that blocking the same enzyme may be even more effective at killing cancer cells. The latter is now the group’s focus. “It’s a great example of how research can start in one place and end up in another,” says Slusher.

Also taking a surprising and promising turn is research going on in the lab of Johns Hopkins neuro-oncologist John Laterra. Laterra has been working on ways to block the action of a molecule called c-Met, found on the surface of brain cells, which  provides a foothold for a growth factor that promotes the aggressive brain tumor called glioblastoma. Partnering with two pharmaceutical companies, Laterra has helped develop a monoclonal antibody that seems to interfere with c-Met’s function, preventing the growth factor from doing its deadly job as a catalyst.

Now it turns out that c-Met may also be critical in providing glioblastomas with a pool of stem cells whose ability to change helps  the tumors develop resistance to treatment. “Inhibiting this pathway will probably make the tumors more susceptible to other drugs,” says Laterra. It’s a big break that could ultimately save lives.

  • Challenge: Translate basic neuroscience research into drugs that help patients
  • Approach: Foster collaborations between basic researchers and experts in drug discovery
  • Progress: New candidate drugs that could help combat schizophrenia and brain cancer

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