Autologous Fetal Tissue Transplant in Parkinson Disease Monkeys Improved Fine Motor Skills, Axon Growth

Parkinson disease (PD) monkeys who received autologous, not allogenic, fetal tissue transplantation exhibited extensive degeneration of dopamine (DA) neuron axon growth and behavioral improvement. These findings were published in Nature Medicine.

Male rhesus macaques had hemiparkinsonism induced by unilateral intracarotid artery injection. They received tissue transplantation (allogenic: n=5; autologous: n=5) derived from dermal fibroblasts with mouse embryonic fibroblast cultures. Behavior was assessed for 8 parkinsonian motor signs captured on video recordings and fine-motor skills were assessed by a food retrieval task. DA neurons and brain health were assessed by magnetic resonance and positron emission tomography (PET) imaging.

Macaques underwent PD induction during ages 5-9 years, 1-3 years prior to cell transplantation. All monkeys exhibited bradykinesia, gait and postural imbalances, slight tremors, and gross motor skill impairments. PET scans indicated all monkeys had >90% unilateral binding potential loss of [¹¹C]DTBZ in putamen and ipsilateral caudate.

Allogenic transplants comprised ~5.5-6 million cells and autologous transplants ~11-22 million cells, such that the number of transplanted DA neurons was similar.

During the 24 months after transplant, the autologous recipients exhibited recovery by means of increased number and speed of movements. These monkeys were able to grasp treats, gait became more natural, climbing more quick, and posture less hunched. The clinical rating scale (CRS) improvement was between 40%-60% among the autologous transplant recipients.

During PET scans, autologous recipients had 366% binding potential increases in ipsilateral putamen (P =.007) and 200% in the caudate (P =.055). The allogenic recipients had 60.9% (P =.25) and 66.7% (P =.64) increases, respectively. In the putamen and caudate of autologous transplant recipients, the graft volumes were measured as 491.5±123.0 mm³ and 158.3±52.5 mm³, respectively. No grafts were detected by PET among the allogenic cohort.

The stained brain biopsy samples indicated allogenic grafts had a clear boundary between donor and host tissues, whereas the autologous grafts often merged with host tissues. The number of TH⁺ cells were 9.11±5.85×10⁴ and 0.61±0.70×10⁴ cells among autologous and allogenic grafts, respectively and maximal distribution of TH⁺ fibers were 222.44±38.75 mm³ and 1.24±0.28 mm³, respectively.

Motor behavioral scores correlated with fine-motor skill (r, -0.7823; P =.022) and CRS (r, 0.7498; P =.03) evaluations and CRS recovery ratio correlated with the putamen (r, 0.7498; P =.03). Total surviving TH⁺ cells correlated with the putamen (r, 0.8170; P =.013), CRS (r, -0.9341; P <.0001), and CRS recovery rate (r, 0.9137; P =.0015).

This study may have been limited by the choice to not compare recovery after transplantation between groups. It remains unclear to which extent the recovery after autologous graft was superior compared with allogenic transplant.

The study authors concluded that with an attempt to mimic future clinical application of stem cell grafts for the treatment of PD, allogenic transplant had fewer beneficial outcomes as observed with autologous transplant.

Disclosure: An author declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Tao Y, Vermilyea SC, Zammit M, et al. Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys. Nat Med. Published online March 1, 2021. doi:10.1038/s41591-021-01257-1