Abstract
Objective: Evaluate the safety and functional activity of human pluripotent stem cell derived neural stem cells (ISC-hpNSC) transplanted into the striatum and substantia nigra of patients with Parkinson’s disease (PD).
Background: Extensive preclinical studies have demonstrated that intranigrostriatal transplantation of cGMP manufactured ISC-hpNSC is safe, well tolerated at high doses and does not induce systemic toxicity or tumors. ISC-hpNSC provides neurotrophic support, immunomodulation and cell replacement which lead to increased dopamine levels and improvement in neurological scores in preclinical PD models. Based on these results, the Australian TGA granted approval to conduct a First-In-Human study to evaluate the safety and functional activity of ISC-hpNSC in PD patients (ClinicalTrials.gov: NCT02452723), making it the world’s first pluripotent stem cell based therapy for PD.
Design/Methods: In this single arm, open label, dose escalating Phase I study, 12 patients, divided into 3 cohorts of 4, are injected with 30, 50 or 70 million ISC-hpNSC. Patients receive stereotactic bilateral injections of 7 cell deposits per hemisphere into the caudate nucleus, putamen and substantia nigra. Patients are evaluated for 12 months with a 5 year long-term follow-up. The primary endpoint is to assess the incidence of treatment-emergent adverse events. Secondary endpoints evaluate clinical improvement compared to baseline using UPDRS, PDQ-39, BDI, CGI, QUIP-RS, AIMS, MOCA, 18F-dopa PET and MRI.
Results: The first patient of the first cohort was successfully transplanted with 30 million ISC-hpNSC. Delivery of the cells went according to plan without any complications or safety issues associated with the administration procedure or immunosuppressive regimen. Interim safety and efficacy data of the rest of the patients of the first cohort receiving 30 million ISC-hpNSC will be presented.
Conclusions: This First-In-Human study suggests that transplantation of ISC-hpNSC is safe and has the potential to slow down disease progression.
Disclosure: Dr. Kern has received personal compensation as an employee of International Stem Cell Corporation. Dr. Garitaonandia has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Gonzalez has received personal compensation for activities with the Iternational Stem Cell Corporation as an employee. Dr. Sherman has received personal compensation for activities with International Stem Cell Corporation as an employee. Dr. Semechkin received compensation for activities with International Stem Cell Corporation as an employee. Dr. Snyder has nothing to disclose. Dr. Shahrul has received personal compensation for activities with International Stem Cell Corporation. Dr. Nair has received personal compensation for activities with International Stem Cell Corporation. Dr. Evans has received personal compensation for activities with Boehringer Ingelheim and Novartis as an advisory board member and from International Stem Cell Corporation.
Letters: Rapid online correspondence
REQUIREMENTS
If you are uploading a letter concerning an article:
You must have updated your disclosures within six months: http://submit.neurology.org
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Use of Whole-Genome Sequencing for Mitochondrial Disease Diagnosis
Dr. Robert Pitceathly and Dr. William Macken