UCSD Trial Recruits for Chronic Cervical SCI Trial

Posted by Sam Maddox in Research News on April 12, 2017 # Research

A team at the University of California San Diego (UCSD) has begun recruiting participants with chronic cervical spinal cord injuries for a clinical trial of neural stem cells.

The trial, sponsored by the Germantown, MD company Neuralstem, follows an earlier Phase I safety trial of the same stem cell line – called NSI-566 – in patients with thoracic injuries. Patients each got six injections for a total of 1.2 million stem cells. That study, which began in 2014, has not been reported in the medical literature but Joseph Ciacci, M.D., the UCSD neurosurgeon who did the implants, presented Phase I safety data in October 2015. He said there had been no serious adverse events and implantation of stem cells in four spinal cord injury patients. Said the company, “The cells have been safe and well-tolerated.”

We reported on the first Neuralstem SCI trial several times, beginning with very encouraging preclinical animal studies from the Mark Tuszynski lab at UCSD. In a 2012 UCSD study, the 566 cell line was transplanted into rats, which recovered significant locomotor function and movement in all lower extremity joints. The study reported that the transplanted neural stem cells became neurons and spawned multiple axons, some extending over 17 spinal segments above and below the level of spinal cord lesion.

From the Tuszynski lab: “… early-stage neurons can overcome the inhibitory milieu of the injured adult spinal cord to mount remarkable axonal growth, resulting in formation of new relay circuits that significantly improve function. These therapeutic properties extend across stem cell sources and species.”

A secondary outcome objective for the SCI thoracic study sought to evaluate whether NSI-566 transplantation could improve motor and sensory scores, bowel and bladder function, and pain reduction. No such details have been revealed.

The 566 cell line, developed from an eight-week human fetal spinal cord, has also been tested in 30 patients with ALS. Those trials results were reported at the American Neurological Association annual meeting in September 2015. Said the company: “Cell transplantation was safe and well-tolerated throughout the escalating doses, reaching a maximum tolerated dose of 16 million cells via 20 bilateral injections. Further, there appeared to be no acceleration in disease progression due to the therapeutic intervention.”

Neuralstem stated last year that a larger, controlled Phase II ALS trial would commence; that has not happened and the company has not indicated when it might.

I spoke with Ciacci today. Because of the apparent safety of the first SCI trial, he said the company was encouraged and confident that its 566 line would be safe in C5 – C7 patients, between one and two years post injury. He acknowledged that because of specific nerve function in the cervical spine area, this area is different than the thoracic spine. “There may be a higher risk,” he said, “but from a technical standpoint, we are confident. There is no reason to suspect that the cells themselves will create any problems.”

What are the 566 cells doing once transplanted? “First, we want the cells to survive,” said Ciacci. “Then we think there is a combination of things that may encourage axonal growth. We think of it as bridging the gap. The cells stimulate the cellular environment, and perhaps provide growth factors that enable axons to grow.”

Ciacci said it is important to initiate trials in the cervical area. “The way I think about it is, can you bring your hand to your face? The patient population we are targeting may have a hard time doing that. Regaining that hand function can be so, so significant for patients.” He noted that there is not a lot of distance nerves have to travel to possibly bring about recovery. “This could mean brushing teeth, feeding one’s self, getting a drink of water. It could allow patients to do a lot of things they couldn’t do before.”

Neuralstem has several other targets for its 566 cell line. Human trials have begun in China for ischemic stroke. Preclinical studies include multiple sclerosis, optic neuritis, brain injury, diabetic neuropathy, Parkinson’s Disease, Huntington’s disease and cerebral palsy. The big question may be, can the company outlast its cash burn long enough to pursue more trials. According to recent federal filings, there is about a year’s worth of money left.

For those interested in the UCSD, contact Ciacci’s office, 619-471-3698, or email Nikki Sidhu, his associate, c/o nksidhu@ucsd.edu

The following inclusion criteria were supplied by UCSD:

1) Have the ability to understand the requirements of the study, provide written informed consent, understand and provide written authorization for the use and disclosure of Protected Health Information (PHI) [per Health Insurance Portability and Accountability Act (HIPAA) Privacy Ruling] and comply with the study procedures

2) Men and women 18-65 years old

3) Women must have a negative serum pregnancy test and practice an acceptable method of contraception or be of non-childbearing potential (post-menopausal for at least 2 years or who have undergone hysterectomy or oophorectomy or surgical sterilization)

4) At least 1 year but no more than 2 years from time of injury at the time of surgery

5) SCI injury classified as AIS-A complete as confirmed by the PI and a Physical Medicine and Rehabilitation doctor or other SCI Medicine board certified physician based on a complete ISNC SCI examination

6) Neurologic level of injury:

a. Group A: within cord segments T2-T12;

b. Group B: injury within cord segments C5-C7

7) Confirmation of bone fusion by CT scan

8) Agree to the visit schedule as outlined in the informed consent

9) All required vaccinations current at the time of enrollment: tetanus/diptheria (TDAP), herpes zoster/shingles (Zoatavax®: within last 10 years and must be prior to surgery), pneumonia (Pneumovax®), seasonal/H1N1 flu vaccines (as appropriate for season). Any missing vaccination will be provided at the screening if consented by the otherwise eligible patient who will then be scheduled for surgery no less than 30 days post vaccination.

Researchers recommend that participants in the trial live within a 500-mile radius of San Diego, due to the intensive, 60-month follow-up schedule.