Approval Granted for Stem Cell Treatment for ALS

The advance enables the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia.

Neuralstem, Inc. (Rockville, MD, USA) updated the progress of its ongoing phase I safety trial of the company’s spinal cord stem cells in the treatment of amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease) at Emory University (Atlanta, GA, USA;). The company announced that, after reviewing safety data from the first 12 patients, the US Food and Drug Administration (FDA) has granted approval for the trial to advance to transplanting patients in the cervical (upper back) region. Until now, patients have received injections in the lumbar (lower back) region only. Earlier in the summer of 2011, the trial’s safety monitoring board unanimously approved moving to the cervical injection phase. The trial will now advance to the final two cohorts of patients with ALS, all of whom will be transplanted in the cervical region of the spine.

“The goal of our cell therapy program is to create therapies that will slow down, stabilize, or reverse, functional deficits in central nervous system [CNS] diseases,” said Karl Johe, PhD, Neuralstem chairman and chief scientific officer. “By moving the cell delivery to cervical spinal cord--the first time the FDA has approved intraspinal injections in this region--we will demonstrate that we can deliver our cells safely and routinely to all parts of the spinal cord.”

The trial is under the direction of lead investigator, Eva Feldman, MD, PhD, director of the University of Michigan (U-M) Alfred Taubman Medical Research Institute (Ann Arbor, MI, USA) and director of research of the ALS Clinic at the University of Michigan Health System, and Jonathan D. Glass, MD, director of the Emory ALS Center. The surgeries are performed by Emory Neurosurgeon, Nicholas M. Boulis, MD.

In a joint statement, the three doctors concluded, “We have successfully treated 12 ALS patients with unilateral or bilateral intraspinal injections of neural stem cells. All of the patients tolerated the procedure without major surgical complications, and there are no indications to date that the stem cells themselves are either toxic or injurious to the spinal cord. Our quantitative clinical assessments showed no evidence of acceleration of disease following stem cell injections, meeting our stated goal of proving safety for this phase I trial. We have cautious optimism that a few of the patients may have slowed in their progression of lower extremity weakness, and one patient may have improved.”

Prolongation of life for patients with ALS will need therapeutic intervention at the level of the cervical spinal motor neurons affecting respiratory function, the investigators reported. “To reach this ultimate goal we plan to move to injections into the cervical spinal cord, which is the next stage of this phase I trial.”

“This is a major milestone for Neuralstem,” said Richard Garr, Neuralstem CEO. Demonstrating the feasibility and safety of transplanting our cells in the upper regions of the spinal cord will have important ramifications for our spinal cord injury program as well as ALS.”

The phase I trial to evaluate the safety of Neuralstem’s spinal cord neural stem cells and intraspinal transplantation technique in ALS patients has been ongoing since January 2010. The trial is designed to enroll up to 18 patients. All of the first 12 patients have been transplanted in the lumbar (lower back) region of the spine. The trial will now progress to the last six patients. The first three of these will receive unilateral injections in the cervical region of the spine. The next three will receive bilateral injections in the cervical region.

Neuralstem is conducting the ongoing FDA-approved phase I safety clinical trial for ALS, which has been awarded orphan status designation by the FDA. In addition to ALS, the company is also targeting major central nervous system disorders with its cell therapy platform, including spinal cord injury, ischemic spastic paraplegia, chronic stroke, and Huntington’s disease. The company has submitted an IND (investigational new drug) application to the FDA for a phase I safety trial in chronic spinal cord injury.

Neuralstem also has the ability to generate stable human neural stem cell lines suitable for the systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may trigger the brain’s capacity to generate new neurons, perhaps reversing the pathologies of some central nervous system disorders. Neuralstem’s first small molecule compound, NSI-189, is currently in a phase I FDA-approved safety trial in major depressive disorder. The phase Ib portion of the trial, in depressed patients, is expected to commence later in 2011. Additional indications for the technology could include schizophrenia, bipolar disorder, and Alzheimer’s disease.

Related Links:
Neuralstem
Emory University
University of Michigan Alfred Taubman Medical Research Institute