An Irvine company could be the first to win federal approval for clinical trials.

COLIN STEWART
Innovation Register columnist

A tiny start-up company in Irvine has a shot at becoming the first to gain federal approval to test an embryonic stem cell treatment in humans.

Two degenerative nerve diseases are the first targets for California Stem Cell Inc.'s therapies. They are ALS, or Lou Gehrig's Disease, which kills adults, and SMA, a fatal disease affecting newborns.

The company hopes to win Food and Drug Administration approval next year to begin clinical trials for both sets of patients.

"Stem cells have the potential to treat every single human disease, but there's a lot that's over-pitched out there," UC-Irvine neurobiologist Hans S. Keirstead told a gathering last week at Bio, aconvention of biotech researchers in San Diego. "What's most difficult is to differentiate the tangibles from a whole bunch of hopeful beginnings."

As chairman of the scientific advisory board at CSC, Keirstead emphasizes the importance of stem-cell companies keeping their focus narrow, setting up operations with an eye to FDA requirements, and using techniques that can be easily geared up for large-scale cell manufacturing.

Founded in 2005 in Irvine right next to UCI, the company followed those guidelines as it laid the groundwork for FDA applications it hopes to file by early 2009 for clinical trials of both ALS and SMA therapies.

Although it's small, CSC has scientific clout. Keirstead helps guide the company in addition to his work in the UCI department of anatomy and neurobiology, the Reeve-Irvine spinal cord injury research center and the Gross Stem Cell Research Center. Also on the scientific advisory panel with him are seven other stem-cell experts from UCI, Johns Hopkins University, the University of Utah, the Burnham Institute, and Ohio State.

They represent a branch of stem-cell research that has been slowed by moral qualms about the need to destroy an early-stage human embryo to extract stem cells, which can grow into any type of cell in the human body.

So far, only one embryonic stem cell company, Geron Corp. of Menlo Park, has filed an FDA application for clinical trials. Geron is pursuing stem-cell-based treatments for spinal cord injuries.

CSC cultivates embryonic stem cells so they grow into billions of nerve cells that could replace defective cells in ALS and SMA patients.

Those stem cells originated from newly fertilized eggs that were discarded by a fertility clinic after the egg donors no longer needed or wanted them, said Chris N. Airriess, the company's chief operating officer.

From a business viewpoint, stem cells' flexibility has a downside.

In theory, these cells from the earliest stages of human development can be coaxed to grow into various types of healthy tissue that could replace any diseased cells – from head to foot, from pancreas to heart to spinal cord.

In practice, however, stem cells' flexibility can be a distraction. Doctors and patients want specific cures, not a stem-cell line with unlimited, unrealized potential.

Investors want results, not a role in a quest for the "future of medicine," biotech analyst Reni Benjamin of the Rodman & Renshaw investment bank told the Bio gathering.

That lesson was important to CSC as a privately owned start-up with just 10 employees.

THERAPY FOR INFANTS

Aiming for quick results, CSC's first focus is on growing cells to treat the devastating genetic disorder Type 1 SMA, or spinal muscular Atrophy.

Affecting fewer than 1,000 infants per year in the United States, the genetic disease causes Motor neurons to degenerate, leaving the baby unable to control its muscles and eventually unable to breathe. Few children with Type 1 SMA live more than a year or two.

"Seeing a one-year-old in a stroller that looks like a stretcher and connected to a Ventilator really opens your eyes fully on why we're doing this," Airriess said. "There's a great opportunity that stem-cell-based motor Neuron treatment will work for them."

The company has already demonstrated in laboratory animals that the treatment leads to regrowth of nerve cells from the spinal cord into the muscles, Airriess said. Beyond that, an independent six-month safety study is under way to make sure that the planned injections wouldn't be toxic or painful, spread uncontrolled, or cause cancer.

The support group Families of Spinal Muscular Atrophy raised $500,000 to pay for the ongoing safety study, he said.

In business terms, Type 1 Infantile SMA represents a $25-million-a-year market, he said.

THERAPY FOR ADULT WITH ALS

Beyond SMA, the company is preparing a treatment for the much better known degenerative disease ALS, amyotrophic lateral sclerosis, also known as Lou Gehrig's Disease.

"ALS is the big major target we're going after," Airriess said.

The disease affects motor neurons that connect the brain, the spinal cord and the muscles, gradually causing loss of muscle control, paralysis and death, usually within a few years of the first diagnosis.

ALS affects an estimated 30,000 people in the U.S., including 5,000 to 10,000 new ALS patients per year. It's potentially a $1-billion-a-year market, Airriess said.

CSC is set up to make billions of motor neurons that could be used either to treat ALS patients directly through cell replacement or to help other researchers screen for new drugs to combat ALS.

FDA-mandated safety studies are already under way.

Important financial support for the company's work on ALS has come from the ALS Therapy Development Institute and the Muscular Dystrophy Association's ALS division. Both are headed by businessman Augie Nieto of Corona del Mar.

In addition, the ALS Association, a patient advocacy group based in Calabasas Hills, is working with the Belgian/English drug testing firm BioFocus DPI, which is searching for a drug to slow or halt the progress of ALS.

BioFocus DPI has contracted with CSC to provide it with billions of human motor neuron cells for use in the search. Payments for the research could total several million dollars if it goes as planned, according to Lucie Brujin, science director for the ALS Association.

Next, CSC says, its stem-cell therapies could be used to treat chronic spinal cord injury and, after that, various types of heart disease.

But those are what the company sees when it looks to the future.

For now, it's keeping its focus on its short-range targets – SMA and ALS.

"We're a small company, so we must keep our blinders on," Keirstead said.

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