An Alternative Novel Therapy for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: Adult Autologous Telomerase-Positive Stem Cells

Abstract

Chronic inflammatory demyelinating polyneuropathy, e.g., chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), is a rare autoimmune mediated peripheral neuropathy. CIDP is defined as symptomology of greater than two months duration and electro diagnostic evidence of peripheral nerve demyelination. The estimated overall prevalence of CIDP is 4.8 to 8.9 cases per 100,000 people. Symptomology includes motor, sensory, and autonomic involvement resulting in symmetrical proximal and distal muscle weakness, loss of strength, areflexia of greater than eight weeks duration, numbness, weakness, sensory ataxia, paresthesia, decreased peripheral temperature, and gait disorder. As CIDP progresses there is axonal loss within mixed peripheral nerves secondary to demyelination, which is associated with a poor prognosis. Autoantibodies identified for CIDP thus far include contactin-1 (CNTN1), contactin-associated protein-1 (Caspr1), contactin-2 (CNTN2), neurofascin-155 (Nfasc-155), neurofascin-140/186(Nfasc-140/186), LM1, gliomedin, and vinculin. Another marker of CIDP is sphingomyelin protein in the cerebral spinal fluid. Potential treatment options for CIDP are first-line therapies, such as corticosteroids, plasma exchange, and/or immunoglobulins. If patients are refractory to first-line treatments to halt progression of the disease, then second-line therapies, such as chemotherapeutic drugs, immunosuppressive drugs, and/or immunomodulatory drugs, are utilized. Lastly, if first- and second-line therapies fail, novel unconventional therapies have been utilized, such as high-dose cyclophosphamide to eradicate a defective immune system containing CIDP-associated autoantibodies to nodal and par anodal proteins. This is then followed with either autologous or HLA-matched allogeneic hematopoietic stem cell transplantation (HSCT) with the intent to replace the defective immune system with a normal immune system absent of CIDP-associated autoantibodies. Whatever therapeutic treatment regimen(s) is/are utilized, maintenance treatments are required for years to maintain stasis in individuals with CIDP. Unfortunately, while first-line, second-line, and/or HSCT treatments may halt the progression of the CIDP and maintain individuals in stasis, they do little to restore neurophysiological function to the individual. We proposed an alternative unconventional therapy to treat CIDP, the use of adult autologous adult telomerase positive stem cells to halt progression of the disease and restore (neuro-) physiological function to the tissues. This hypothesis was based on previous clinical studies utilizing telomerase positive stem cells with Parkinson disease, Alzheimer’s disease, age- related dry macular degeneration, traumatic blindness, traumatic spinal cord injury, myocardial infarction, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, celiac disease, systemic lupus erythematosus, and osteoarthritis. Within this small cohort (n=3) clinical study, there were no adverse events reported for any participant treated. While there was no direct proof that the autologous telomerase positive stem cells contributed to the results seen in two of these participants, there was indirect proof for restoration of neurophysiological functions. This was demonstrated with respect to return of motor, sensory, and autonomic functions, e.g., increased strength, return of sensory input, return of reflexes, loss of numbness, increased blood flow, normal body temperature in extremities, and normal gait. Indirectly, this suggested that autologous telomerase positive stem cells are safe and demonstrate a 66% efficacy with respect to halting progression of chronic inflammatory demyelinating polyneuropathy and restoration of neurophysiological functions.