First-in-human Phase 1/2a Study of Intracerebral Transplantation using Embryonic-derived Neural Stem Cells (NR1) for Chronic Ischemic Stroke

Saturday, May 4, 2024

2:37 PM – 2:43 PM CT

Location: S403ab

Presenting Author(s)

Gary K. Steinberg, MD, PhD

Professor
Stanford University School of Medicine
Stanford, California, United States

Co-Author(s)

AB

Anthony Bet, MBA

Clinical Manager
Stanford University, United States
MC

Maria Coburn, BS

Clinical Operations Manager
Stanford University, United States
RD

Robert Diaz, PhD

Life Science Research Assistant
Stanford University, United States
SH

Summer Han, PhD

Associate Professor (Research) Neurosurgery and Medicine
Stanford University, United States
KM

Kathy McDonald, BS

Clinical Research Coordinator
Stanford University, United States
FQ

FeiFei Qin, MPH

Biostatician
Stanford University, United States
CS

Cindy Samos, BA

Project Manager
Stanford University, United States
NS

Neil Schwartz, MD, PhD

Clinical Professor Neurology
Stanford University, United States
Gary K. Steinberg, MD, PhD

Professor
Stanford University School of Medicine
Stanford, California, United States
ET

Elizabeth Tong, MD

Clinical Assistant Professor
Stanford University, United States
KT

Kirk Trisler, PhD

Consultant
Stanford University, United States
JW

Judy Weissinger, MD

Consultant
Stanford University, United States
JW

Jennifer Williams, BS

Senior Occupational Therapist
Stanford University, United States

Disclosure(s):

Gary K. Steinberg, MD, PhD: Carl Zeiss Meditech AG: Consultant (Ongoing); Peter Lazic, US: Royalty Recipient (Ongoing); SanBio: Consultant (Ongoing); Surgical Theater: Consultant (Ongoing)

Introduction: No treatment exists to restore function in chronic stroke patients. Several prior intracerebral stem cell trials were promising, but are not being further developed.

Objective
NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models, and expanded to GMP cryopreserved Cell Lots (P18). The safety & efficacy of NR1 intracerebral transplantation in chronic stroke patients was assessed (NCT04631406).

Methods: Inclusion: 18-75 yo; 6-60 mos post-ischemic MCA stroke; mRS 3-4. Subjects transplanted with 2.5M, 5M, 10M or 20M cells. Primary Outcomes: Adverse events 0-6 mos; Change in Fugl-Meyer (FM) total motor score (max 100) at 6 & 12 months. Other outcomes: Gait Speed, Barthel Index, NIHSS, mRS, MRI DTI, FLAIR, Resting State fMRI and FDG PET.

Results: 14 patients were transplanted. Adverse events included headache and worsened speech, all resolving spontaneously. All 13 pts with f/u ≥1 mos demonstrated improved total FM motor and BI. At 6 mos, 7/12 subjects & at 12 mos 5/7 showed clinically meaningful recovery in FM total (≥10 pts), & patients increased 9.7 points (SEM 1.4) for total FM motor, 7.9 points (SEM 2.5) for BI, while gait improved 9.2 m/s (SEM 4.5.) Linear regression showed mean improvement in total FM motor, UE motor and LE motor score at 12 mos (p=0.0001, p=0.008, p= < 0.0001), with significant differences in total FM motor and BI at mos 6 (p < 0.05).
11/14 pts demonstrated new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which in prior studies was highly correlated with sustained neurologic recovery. Resting state fMRI showed improved functional brain connectivity in sensorimotor network, both ipsilesionally & contralesionally. DTI demonstrated increased integrity of the ipsilesional CS tract in the cerebral peduncle. FDG PET showed increased activity in ipsilesional motor cortex & contralateral cerebellum.

Conclusion : Intraparenchymal transplantation of NR1 cells in chronic stroke patients appears safe and well tolerated. Results suggest improved motor function starting at 1 mos and increasing to 12 mos post-implant.