Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia
Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia
Brain lesions in the adult have dramatic consequences, because the spontaneous capacity of
 the brain to functionally recover is limited. Besides existing rehabilitative therapeutic
 approaches (e.g. physiotherapy), several lines of research aim at developing treatments to
 promote and refine brain plasticity to enhance functional recovery following brain injury.

 This pilot clinical study aims at enrolling subjects victim of a stroke with neuronal
 destruction leading to a disabling motor deficit. Usually these patients benefit from
 intensive neurorehabilitation which allows them to progress up to a certain point but when
 their recovery plateau is reached; current medicine is disarmed and no effective treatment
 allows, to date, to improve further their performance. This monocentric pilot study aims at
 evaluating the feasibility and safety of Autologous Neural Cell Ecosystems (ANCE), which is a
 cortical autograft intended to be used on stroke patients, for the replacement of motor
 neurons destroyed during an ischemic stroke.
Using neural grafts to restore function after lesions of the central nervous system is a
 challenging strategy. Most of the transplantation experience acquired the last decades was
 focused on fetal neuronal grafts. However, despite the great enthusiasm generated by this
 approach, ethical controversies, immune rejection, and lack of fetal donors remain a major
 problem. Therefore, autotransplantation of adult brain cells represents an attractive
 restoration alternative to bypass the caveats of fetal grafting.

 The optimization of the procedure to obtain ANCE, a cortical autograft obtained from cortical
 biopsy, was first successfully demonstrated in producing long-term primary culture of adult
 human brain cells from temporal lobe tissues obtained from epilepsy and trauma neurosurgical
 patients. ANCE has been characterized as an ecosystem of autologous neural cells in
 suspension, composed of several cell types: astrocytes, proliferative progenitors and
 quiescent progenitors.

 The production of ANCE has been implemented to prepare long-term primary culture from primate
 cortical biopsies. This allowed assessing the feasibility of autotransplantation from brain
 biopsy to reimplantation of cultured brain cells in a non-human primate model of motor cortex
 lesion. On the same model of cerebral cortex lesion in nonhuman primates, further study
 demonstrated, by quantitative behavioral evidence, the beneficial outcome of cell therapy
 following injury of the cerebral cortex.

 Based on the encouraging results from past experiences on non-human primate model of motor
 cortex lesion, this monocentric pilot study aims at evaluating the feasibility and safety of
 ANCE (Autologous Neural Cell Ecosystems), which is cortical autograft intended to be used on
 stroke patients, for the replacement of motor neurons destroyed during an ischemic stroke.
Inclusion Criteria:

 -  Be between 18 and 75 years old.

 -  Victim of a first ischemic stroke in superficial Sylvian territory with at least
 frontal damage.

 -  Cerebral ischemic lesion demonstrated by MRI.

 -  Stroke older than one year.

 -  Presence of a motor hemi-syndrome with at least one involvement of the upper limb.

 -  Stable neurological deficit in motor function of the limb greater than two months
 apart before enrolling the patient in the study.

 -  Woman of childbearing potential with a negative blood pregnancy test before the biopsy
 and using a reliable method of contraception during the study.

 -  Patient capable of discernment and of giving informed consent himself.

 -  Absence of other serious pathologies or comorbidities.

 Exclusion Criteria:

 -  Brain lesions or a history of stroke or brain hemorrhage.

 -  Signs of peripheral neurological damage, such as radicular or trunk involvement

 -  History of spinal cord problems.

 -  History of neurosurgical intervention in the brain.

 -  surgical intervention contraindications.

 -  Anticoagulation, if it cannot be interrupted one week before and one week after each
 of the 2 brain surgeries.

 -  Coagulation disorders.

 -  Treatment of botulinum toxin during the last 3 months before inclusion.

 -  Seizures or anti-epileptic treatment.

 -  Global cognitive disorders, such as degenerative or vascular dementia.

 -  High blood pressure difficult to control.

 -  Alcohol or drug abuse.

 -  Known neoplasia.

 -  Inability to understand or cooperate in the study.

 -  MRI contraindication

 -  Pregnancy

 -  Penicillin intolerance or allergy