Daniel S. Levine

A doctor threads a catheter through the jugular vein of a heart transplant recipient and manipulates it to the patient's heart to remove tissue samples to check for signs that the body's immune system is attacking the transplanted heart.

The procedure is repeated nearly once a month for new heart recipients and then gradually tapered to about once a year as doctors continue to monitor and adjust the immunosuppressants that heart transplant patients must take for the rest of their lives.

The procedure is expensive, invasive and unpleasant. With an estimated 30,000 patients living with heart transplants, such biopsies are performed about 100,000 times a year at a cost of as much as $5,000 per treatment. But a small South San Francisco-based company has an alternative test for what it sees as a $100 million market.

XDx Inc., a molecular diagnostics company, has developed a method for monitoring heart transplant rejection. Its diagnostic technology AlloMap uses a simple blood sample to search for a group of 20 genes that would indicate the immune system is firing up and readying to attack the transplanted heart before damage is done.

"It is not only safe and efficacious and quality of life-enhancing for the patient, but it also cost effective," said Dr. Mario Deng, director of cardiac transplantation research at Columbia University and the principal investigator on a five-year study of XDx's test involving eight translation centers. "Every patient wants non-invasive testing as opposed to having their neck stuck with a heart catheter."

Founded in 2000, XDx is at the vanguard of a range of new diagnostic products made possible by the genomics revolution that promises to alter the standard practices of medicine and usher in a new era of so-called personal medicine.

The company raised a total of $44 million from a group of blue-chip venture investors, including Kleiner Perkins Caufield & Byers, TPG Ventures, Sprout Group, Bay Area Equity Fund (managed by J.P. Morgan Integral Capital Partners) and Burrill & Co.

Once a doctor draws blood from a patient, it is sent overnight to XDx's lab, where the company tests the samples to find a number of genes associated with the immune system readying to attack a transplanted heart. The lab reports a score on a scale of 0 to 40 to indicate how actively the immune system is or is not ramping up to attack.

A study published in the American Journal of Transplantation estimated the cost savings of using the test to be between $5,000 and $30,000 a year per patient.

"We are using fairly sophisticated gene expression tests combined with very advanced data processing to give a very precise metric for doctors to look into the activity of the immune systems for an individual patient at a certain point in time," said Pierre Cassigneul, CEO of XDx.

XDx's lab received Clinical Laboratory Improvements Amendments certification in November 2004 and has been working this year to launch its AlloMap molecular expression tests. The company, which said it is now in the process of converting the cardiac transplant centers that participated in its validation trial of its tests into commercial customers, did not offer specific sales numbers.

The heart transplant diagnostic is the first of what the company expects will be several diagnostics that will be used to monitor the immune systems of patients with transplants. The next product the company expects to launch will be one to monitor patients with lung transplants.

The company is also developing tests for a number of autoimmune diseases such as Lupus or Crohn's disease.

Brook Byers, a partner with the venture capital firm Kleiner Perkins Caufield & Byers and chairman of XDx, said he expects XDx will develop pairs of tests for autoimmune disease with one to actually diagnose the disease and the other to monitor patients to alert doctors prior to the onset of a flare of the disease when the immune system fires up to attack a particular system or organ.

In each case, the company must identify a collection of genes that serve as the unique biomarkers that signal the immune systems is readying to attack a particular organ or system in the body.

"We're working to have the same ability to anticipate the flare to provide an early warning to the clinician to be able to treat the damage before there is damage," he said.

Snapshot:

Business: Develops and markets molecular diagnostics to monitor the immune system of transplant patients and people with autoimmune diseases.
Headquarters: South San Francisco.
CEO: Pierre Cassigneul.
Founded: 2000.
Funding: $44 million. Investors: Kleiner Perkins Caufield & Byers, TPG Ventures, Sprout Group, Integral Capital Partners, Burrill & Co. and Bay Area Equity Fund (managed by JP Morgan).
Employees: 60.

Daniel S. Levine is a reporter for the San Francisco Business Times.