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.