Pediatric Grand Rounds (CME): Beyond Blood: Transplant and Gene-Edited Cell Therapy for Neurodegenerative Disease in Children

Beyond Blood: Transplant and Gene-Edited Cell Therapy for Neurodegenerative Disease in Children

PRESENTER:
Natalia Gomez-Ospina, MD, PhD
Assistant Professor of Pediatrics, Medical Genetics
Stanford School of Medicine

 

SESSION DESCRIPTION
Allogeneic hematopoietic stem cell transplantation is standard of care for a small number of neurodegenerative inherited disorders — metachromatic leukodystrophy, Krabbe disease, X-linked adrenoleukodystrophy, and severe MPS type 1 — yet outcomes remain disappointing for most patients. Donor-derived cells repopulate the CNS slowly and incompletely, so neurologic decline often outpaces engraftment, while myeloablative conditioning and graft-versus-host disease impose morbidity that narrows the risk-benefit window. With newborn screening now detecting many of these disorders before symptom onset, the principal constraint on outcomes is no longer early diagnosis but the limitations of available therapy. This session reviews two developments that may substantially improve outcomes for these patients. The first is a conditioning strategy that pairs brain-penetrant chemotherapy with transient CSF1R inhibition, which in preclinical models achieves near-complete microglial replacement within weeks rather than months. The second is autologous transplantation of hematopoietic stem cells gene-edited at the CCR5 safe harbor to secrete supraphysiologic enzyme, eliminating the need for a matched donor and the risk of GVHD. Data will be presented across MPS type 1, Gaucher disease, and Friedreich’s ataxia, including evidence that engrafted myeloid cells benefit surrounding tissue not only through enzyme cross-correction but also by transferring intact mitochondria, with improvements in both neurologic and cardiac endpoints. The session closes with the manufacturing, genotoxicity, and regulatory requirements that stand between these results and first-in-human trials.

 

EDUCATION GOALS

• Describe the current indications for hematopoietic stem cell transplantation in inherited neurodegenerative disease and the clinical factors — delayed CNS engraftment, conditioning-related toxicity, and graft-versus-host disease — that limit its benefit in rapidly progressive disorders.
• Differentiate the mechanisms by which engrafted donor myeloid cells correct disease in the CNS and other tissues, and apply this understanding to anticipate which disorders and which patients are most likely to benefit.
• Assess the preclinical efficacy and safety evidence for autologous hematopoietic stem cell products in lysosomal storage disorders, and identify their implications for patient counseling, timing of referral, and future trial eligibility.
   

LOCATION (in-person)
Center for Academic Medicine
Grand Rounds Room
453 Quarry Road, 
Palo Alto, CA 94304

 

ZOOM INFORMATION
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CME ACCREDITATION
This session is eligible for CME credit. To claim CME credit, text code to (844) 560-1904 to confirm attendance. A new code will be provided at beginning of the session.