By Frances Bishopp

Staff Writer

MitoKor Inc., a privately held San Diego pharmacogenomics company, has completed a $16.1 million venture capital round of financing to support drug and diagnostic development programs based on the role of mitochondrial DNA mutations in various disorders, including Alzheimer's and Parkinson's diseases.

The financing was led by Domain Partners III L.P., of Princeton, N.J., and Biotechnology Investments Ltd., of London, and included existing investors: Alta Partners, of San Francisco, Forward Ventures, of San Diego, MDS Capital Corp., of Toronto, Biotechvest L.P., of Chicago, Sorrento Ventures, of San Diego, Sofinnova Ventures III, of San Francisco, and ThornerVentures, of San Francisco.

MitoKor, was founded in 1992 under the name of Applied Genetics Inc. Its core technology is based on the identification of specific alterations in mitochondrial DNA associated with late-onset degenerative diseases of neurological, psychiatric and metabolic importance.

The company also is developing transgenic animal models by inserting human mitochondria into mouse embryonic stem cells.

Called the bioenergetic engines of the cell, mitochondria are cellular organelles responsible for generating the energy needed to sustain life. A cell can contain up to 1,000 or more mitochondria, each with its own DNA (mitoDNA) inherited solely from the maternal line. MitoDNA is separate and distinct from nuclear DNA and is located in the cytoplasm of cells and not the nucleus.

MitoDNA carries information that is required to produce the enzymes necessary for energy metabolism. When mitochondria fail, progressive bioenergetic impairment ensues, followed by the production of toxic substances and abnormal regulation of intracellular ions.

In addition to funding MitoKor's main programs in Alzheimer's disease, Parkinson's disease and late-onset diabetes mellitus, the newly raised funds will be used for work in diagnostics and therapeutics to give the company a "much better balance sheet to work off of," Walter Moos, chairman and CEO of MitoKor, told BioWorld Today.

In the Alzheimer's program, Moos said, MitoKor is linking diagnostics and therapeutics together as "therametrics," where the diagnostics help in the process of choosing the patients most likely to respond to a treatment.

"We have found alterations in the mitochondrial DNA in patients with Alzheimer's, Parkinson's or late-onset diabetes, which we use to characterize the patients and monitor whether the drug is changing the genetic balance at all. We then use what we have learned through these genetic profiles to establish drug discovery assays," Moos said.

In the Alzheimer's program, Moos said, MitoKor has identified defects in Complex IV of the electron transport chain, which is involved in the production of energy for cells.

MitoKor has identified, in particular, alterations in the mitochondrial DNA that codes for proteins in Complex IV. With this mitoDNA, MitoKor has established a blood-based diagnostic test.

"We have also taken what we have learned from this to establish a series of different biochemical assays, in fact, cellular models of the disease, that show all of the hallmarks of Alzheimer's," Moos said.

MitoKor then screens for drugs and, according to Moos, the company has "some early hits." In the diagnostic area, he added, the company now has data on approximately 2,000 patients.

In the area of Parkinson's, MitoKor has traced alterations in the mitochondrial genome to those that code for proteins in Complex I. A link has been shown to the Complex I defect and MitoKor is currently beginning to set up models.

In late-onset diabetes, the company has traced alterations of mitochondrial DNA to Complex V and is developing diagnostics and therapeutics from that point. "We are looking for small molecules and the hope is that we could alter the balance of the different mitochondrial genomes to the healthier genomes," Moos said, "and, as a result, either delay the onset of these diseases or reverse them."

In May, 1996, MitoKor completed a $10.6 million venture capital financing. "We have many years of funding at this point," Moos said. *