The frequency of exact diagnosis and confirmation of hereditary ataxias has risen in tandem with advances in genetic testing that define the different types and the locus of genotype variation, abnormalities within chromosomes and proteins. Mutational analysis can correlate with apoptosis, necrosis or degeneration of neurons in the cerebellum, brain stem, or spinal cord. The rate and quantity of atrophy and degeneration of neurons differ with the various types of hereditary ataxia and patients' ages. The pathological neuronal loss results in loss of cerebellospinal tracts and functional disorders. The physical manifestations translating to functional disability include unsteadiness in walking, wide-based steps, inability to heel walk, unsteadiness in standing or sitting, dependence on a walking frame, walking aid or wheel-chair, dysarthria and dysphagia. Despite genotypic variability, the phenotypic symptoms among patients are mostly similar, only differing in ages of onset or rates of progression. According to the iconography records of the FRDA subjects in this study, the onset of cerebellar atrophy is approximately five years before symptoms appear and the progression is in direct proportion to the atrophy ratio of cerebellum and spinal cord. Patients eventually develop severe functional impairment of swallowing, loss of locomotor capacity and even death due to respiratory muscle paralysis or pulmonary infection.
Prior studies attempt to treat neurodegenerative diseases with human embryonic olfactory ensheathing cell  and neural stem cell [17, 23] transplantation. However, there are no publications documenting systematic study of hereditary ataxia treatment with CBMCs. Based on our clinical experience, the short-term effect of CBMC transplantation combined with rehabilitation training on equilibrium function treating hereditary ataxia was significant. After receiving one treatment course, the patients were evaluated by physicians and therapists using BBS, a validated functional scale that measures the ability to walk, balance while standing and other activities of daily living for ataxia patients .
The average duration of symptoms of the subjects enrolled was over 10 years, and therefore, most received equilibrium function training without significant improvements prior to CBMC treatment. One of the patients with SCA6 who needed complete support while walking and had abnormal Romberg sign (+), heel-knee-tibia test (+) and heel test (+) at baseline, subjectively felt marked improvements immediately after the CBMC transplantation and could objectively walk without support. He also finished the heel test after three CBMC transplantations. In addition, this subject's condition remained stable three years after the treatment according to the follow up examinations.
One family from Saskatchewan, Canada had 32 individuals with confirmed SCA2 from 80 tested family members spanning four generations. Sixteen members of the family had already expired directly from the disease or complications stemming from it. Six male siblings or children from this family participated in the trial. The symptoms in the third generation were relatively mild and all were able to move with support. However, in the fourth generation, symptoms started by age 16 years old. Moreover, all signs and symptoms continued to progress. By age 19, when one fourth generation family member participated, he had already lost his ability to walk. After one course of treatment, his BBS score rose from 26/56 to 43/56. Unfortunately, because of geographical distance, it was impossible to provide long-term follow-up details on all patients who received the treatment.
The interval between baseline and post-treatment of serum IgG, IgA, IgM, C3, C4 and T cell subsets tests, as per protocol, was about a month. IgG, IgA, total T cells and CD3+CD4 T cells decreased significantly after treatment (P < 0.01). Although there are numerous proportioned mechanisms of action, one possibility is that CBMCs exercise broad inhibitory action on cellular and humoral immunity. One limitation of the study was that some patients received treatment with CBMC for 20 days in total, whereas others received up to 42 days in total. There were no significant differences in immunological profiles or clinical responses between the 20 to 42 day treatment groups, however this is a question that may be addressed in future studies.
Cord blood derived cells are being investigated in a myriad of preclinical disease models [18, 19, 24, 25]. The safety of CBMC transplantation has been investigated in several human clinical trials with neurodegenerative conditions and has not revealed any severe adverse events, immune reactivity or Graft-versus-host-disease [16, 26, 27]. The potential concern regarding GVHD induced by allogeneic cord blood administered in absence of immune suppression is mitigated by the fact that hundreds of administrations of allogeneic lymphocytes have been performed in women with recurrent spontaneous abortions as a method of immune modulation, without GVHD being observed . Mechanism studies suggest that multi-potent cells in the heterogeneous CBMC population may not only differentiate into osteoblasts, chondroblasts, adipocytes and neurons and astrocytes to act as a cell replacement source, but also produce antioxidants, several neurotrophic and angiogenic factors and modulate immune and inflammatory reaction [19, 28, 29]. Intravenously administered CBMCs enter brain, survive, migrate, improve functional recovery and reduce infarct volume in the middle cerebral artery occlusion rat stroke model through the action of anti-inflammatory, neuroprotection and neovascularization [30, 31]. Cord blood stem cells infusion into the systemic circulation of G93A mice, an amyotrophic lateral sclerosis (ALS) model, delayed disease progression for 2-3 weeks and increased lifespan of diseased mice by providing cell replacement and protection of motor neurons . Transplantation of hUCB cells into the spinal cord injury (SCI) rats most likely inhibits the apoptotic cascade which is followed by axonal remyelination, regeneration of the damaged neural tissues, potential restoration of blood flow to the damaged area by neovascularization, and modulation of the immune/inflammatory response to the injury [33, 34]. Accordingly, these multiple restorative and protective effects from CBMC grafts may act in harmony to exert therapeutic benefits for hereditary ataxias, but the exact mechanism of action still remains unconfirmed.