Neuralstem Inc., the tiny Rockville biotech whose human stem cells have helped paralyzed rats walk again, is poised to launch its first trials on severe spinal cord conditions in humans.
The 11-year-old company is finally readying for trials of its patented nerve stem cell products on the first three of its possible targets: traumatic spinal cord injury; another type of paralysis often associated with stroke; and amyotrophic lateral sclerosis, known as Lou Gehrig’s disease. There are no cures for the conditions.
In a study at Johns Hopkins, Neuralstem stem cells extended the life of rats with a form of ALS.
‘These stem cells not only survived in an extremely adverse Environment, but may have actually produced and delivered Motor Neuron growth factors, which promote growth and function, to the sick motor neurons,” said Vassillis E. Koliatsos, whose lab conducted the study.
Oddly, for a biotech at least, Neuralstem is not banking on a sea of ready cash to navigate through costly clinical trials, but on a boatload of confidence, built through methodical outsourcing.
The company has enough cash to complete only one of three planned clinical trials. Officials expect early results to attract a rush of investors to help it finish trials and market treatments.
‘‘Our plan does assume that we can help paralyzed people. It’s clear from a business point of view it will be no problem in raising additional funds after the first phase” of clinical trials, said Richard Garr, co-founder, president and CEO.
While other studies have reported only limited success with spinal cord-injured rats, ‘‘we made them walk again,” said Neuralstem’s scientific founder and chairman, Karl Johe. ‘‘We do expect the same thing in humans but it is more complicated.”
Such injuries in humans are more variable, but he would have expected the treatment to have worked for paralyzed actor Christopher Reeve.
Grafts of Neuralstem’s stem cells into 16 rats three weeks after they were paralyzed showed a ‘‘progressive recovery of ambulatory function” in studies at the University of California, San Diego. The results were reported in the journal Neuroscience in June.
The company’s first human trials on a neurological disease will be to treat ALS — Lou Gehrig’s disease — which weakens muscles from the loss of nerve cells in the brain and spinal cord, eventually leading to death.
But first, Neuralstem expects to file a new investigative drug application next month with the U.S. Food and Drug Administration for human trials of its spinal cord stem cell treatment for ischemic spastic Paraplegia. This paralysis results from blood shortage from the kind of stroke that can follow surgery or an injury such as a gunshot wound.
Garr anticipates filing a second application with the FDA next year for traumatic spinal cord injury.
‘A real dose,to real patients’
Garr and Johe think Neuralstem has two advantages.
First, the company has completed a massive scale-up of its stem cells at Charles River Laboratories in Wilmington, Mass.
Second, unlike phase 1 trials for drugs, the stem cell therapy will involve actual nerve-damaged patients, not healthy volunteers enrolled only to measure the treatment’s safety.
‘‘It will be a real dose, to real patients, given the first time. You can’t do this with healthy volunteers,” Garr said. Any effect of the therapy will be seen early in the trials.
Garr believes ‘‘without question” that the cells are beneficial to patients, but that the key to therapeutic success will be to find the optimal amounts and best way to administer the treatment in different types of patients.
Company officials also think they have cleared the major barrier of reproducibility, which Garr calls a primary reason for a lack of successful stem cell therapies.
Despite the promise reported in popular media, embryonic stem cells are notoriously difficult to reproduce, Garr said.
‘‘When you grow them up, you might not get the same thing,” he said.
Before scaling up the cells, Neuralstem created a robust and reproducible ‘‘super clone” of cells that Johe discovered from fetal tissue when he worked at the National Institutes of Health a dozen years ago.
Little cash,high costs
The company’s latest financial figures appear to fall short of covering the usual expenses of clinical trials that can run in the hundreds of millions of dollars.
Neuralstem’s net loss for the nine-month period ended Sept. 30, was $4.2 million, with $306,000 in revenues. Assets totaled $5.3 million.
Almost all of its expenses have been covered by sales of stock. In the short history of stem cell companies, investors have been far from enthusiastic and Neuralstem’s stock has stayed largely under the Wall Street radar. Even after last week’s announcements that scientists converted skin cells into embryonic-like stem cells — a major breakthrough, according to some scientists — stocks of leading stem cell companies didn’t advance.
Manufacturing the company’s stem cell products may be much more expensive than most other drugs currently on the market, according to Neuralstem’s SEC filings.
One trial will cost from $100,000 to $150,000 per patient, or about $1.5 million for a phase 1 trial for 10 to 12 patients.
The company may issue more common and preferred stock and is actively seeking manufacturing and distribution partners.
It has retained Quintiles Inc. to help with regulatory compliance, applications and patient enrollment. Garr also expects to sign an overseas partner before the first trial to develop markets in Asia.