Biology subjects

Daadi, M. M.

Publications and source records attributed to Daadi, M. M..

3 recordsLinked to original sources

bioRxiv2026

Regenerative Neural Stem Cell Therapy Improves Multidomain Neurological Deficits after Traumatic Brain Injury in Nonhuman Primates

Traumatic brain injury (TBI) produces persistent multidomain disability spanning motor, cognitive, emotional and sleep-wake function, with no approved restorative therapy. Here, we tested pd.S6.133.hNSC, a cryopreserved, GMP-like human neural stem cell (hNSC) product derived from Shef-6 and FACS-sorted on CD133+/CD34-, in a randomized dose-ranging study in common marmosets subjected to controlled cortical impact (n = 18). Seven weeks after injury, animals received MRI-guided stereotactic transplantation into perilesional cortex bilaterally under tacrolimus immunosuppression, with either vehicle or pd.S6.133.hNSC at 1 million (1e6) or 5 million (5e6) cell dose. At 3 months post-transplantation, 5e6 dosage improved executive and problem-solving performances (Object Retrieval Task with Barrier Detour), gait dynamics (CatWalk assay), anxiety-like behavior (Human Intruder Test), and actigraphy-derived sleep-wake and circadian rhythm measures relative to vehicle and 1e6 dose. Longitudinal 7T MRI demonstrated a dose-dependent reduction in lesion volume and preservation of corpus callosum white matter volume in the 5e6 group. Transplantation was well tolerated, with no observed adverse events across 1,197 cumulative post-transplant animal-days. Histopathology at 3 months post-transplantation in NHPs showed engraftment without tumor formation or abnormal tissue overgrowth. These findings support the safety and multidomain efficacy of a cryopreserved hNSC product in a nonhuman primate TBI model and inform translational development toward first-in-human testing with clinically aligned endpoints.

neuroscience↗

bioRxiv2025

Human-specific features of the cerebellum and ZP2-regulated synapse development

Understanding the unique features of the human brain compared to non-human primates has long intrigued humankind. The cerebellum refines motor coordination and cognitive functions, contributing to the evolutionary development of human adaptability and dexterity. To identify shared and divergent features across primates, we conducted single-nucleus transcriptomic and chromatin accessibility profiling of the adult cerebellar cortex in humans, chimpanzees, macaques, and marmosets. We revealed human-specific transcriptomic and regulatory features, particularly those involved in synaptogenesis. Notably, we identified an enrichment of the sperm receptor zona pellucida glycoprotein 2 (ZP2) and its potential interactors, known for their roles in gamete interaction, in human granule cells. Experimental data show that ZP2 expression in human granule cells is induced by pontine mossy fibers, reducing synaptic proteins at pontocerebellar glomerular synapses, and decreasing cerebellar neuron electrophysiological activity. This unexpected co-option of ZP2 in human-specific synapse regulation provides insights into the evolutionary specialization of the human cerebellum.

neuroscience↗

bioRxiv2021

Dopamine D3 Receptor Ligand Suppresses the Expression of Levodopa-Induced Dyskinesia in Nonhuman Primate Model of Parkinson's Disease

Parkinsons disease (PD) is a complex multisystem, chronic and so far incurable disease with significant unmet medical needs. The incidence of PD increases with aging and the expected burden will continue to escalate with our aging population. Since its discovery in the 1961 levodopa remains the gold standard pharmacotherapy for PD. However, the progressive nature of the neurodegenerative process in and beyond the nigrostriatal system causes a multitude of side effects, including levodopa-induced dyskinesia within 5 years of therapy. Attenuating dyskinesia has been a significant challenge in the clinical management of PD. We report on a small molecule that eliminates the expression of levodopa-induced dyskinesia and significantly improves PD-like symptoms. The lead compound PD13R we discovered is a dopamine D3 receptor partial agonist with high affinity and selectivity, orally active and with desirable drug-like properties. Future studies are aimed at developing this lead compound for treating PD patients with dyskinesia.

neuroscience↗