Neural Stem Cells Show Early Promise in Phase 1 Trial as Treatment for Parkinson’s

Patients with moderate-to-severe Parkinson’s disease who received human neural stem cells in their brain as part of a Phase 1 trial are performing better at six months than they were at the start of the study.

Also, all patients are meeting the trial’s primary goal of safety, according to a news release from International Stem Cell Corporation, or ISCO, a clinical-stage biotech based in California.

“We are already seeing some positive efficacy results six months post-transplantation in this 12-month study,” Russell Kern, PhD, ISCO’s executive vice president and chief scientific officer, said in the press release. “While the relatively small sample size makes it difficult to observe statistically significant differences, the interim efficacy results are very encouraging.”

The Phase 1 study (NCT02452723), which is still recruiting participants, aims to demonstrate the safety and tolerability of International Stem Cell’s human parthenogenetic neural stem cells (ISC-hpNSC) as a potential therapy for Parkinson’s disease.

Patients will receive a specific dose of ISC-hpNSC – from 30 to 70 million neural stem cells – injected directly into the striatum and substantia nigra regions of the brain.

They will then be carefully monitored for 12 months at specified time-points. The effects of the therapy will be evaluated using several neurological tests, including the Unified Parkinson Disease Rating Scale (UPDRS).

PET scans will be conducted at the start of the study and at six and 12 months after the stem cell transplant. Patients will be followed for five additional years to monitor the treatment’s safety and disease progression.

Using animal models of Parkinson’s disease, researchers showed that injecting ISC-hpNSC was safe and improved the animal’s motor symptoms, increased their dopamine levels, and rescued the number of dopaminergic neurons compared to controls.

Now, researchers hope that a single transplant of ISC-hpNSC into the brain of Parkinson’s patients can increase the population of dopaminergic neurons and halt further neuronal destruction.

Six months after receiving 30 million ISC-hpNSCs, patients in the first trial group showed a 24 percent reduction in their OFF time – a period when levodopa therapy begins to fail and symptoms return. The therapy also extended levodopa’s period of action without dyskinesia – known as ON time – by 19 percent.

All patients were seen to have an improved mood at six months, with an average increase of 35 percent in the Beck Depression Inventory and 33 percent in the Parkinson’s Disease Quality of Life Score-39 (PDQ-39). Also, patients had either retained or improved their cognitive abilities, with an average improvement of 14 percent in the Cognitive Impairment dimension of PDQ-39.

Conducting daily routine activities was also easier for these patients, who had average improvements of 22 percent in Activities of Daily Living and 15 percent in Mobility dimensions of PDQ-39.

The Bodily Discomfort dimension of PDQ-39 also improved on average by 12 percent.

Meanwhile, patients experienced a 53 percent decrease in their impulsive and compulsive disorders.

The therapy was found to be safe, without any serious adverse events, including the risk for tumors, cysts, enhanced inflammation or infection, meeting the trial’s primary goal.

“The first dose tested was used to determine the safety and tolerability of ISC-hpNSC therapy and is below the optimal therapeutic dose established in our preclinical studies,” Kern said. “We are anticipating strong results in the second cohort (receiving a higher dose of cells) in which two patients have been treated already.”

These interim Phase 1 trial results are building a strong foundation to lead to Phase 2 clinical trials in Parkinson’s and traumatic brain injury, “which are some of the biggest current unmet medical needs,” Kern said.