Multiple sclerosis (MS):

Multiple sclerosis (MS) affects more than 2 million people worldwide and is the most common non-traumatic cause of disability primarily amongst American and European adults. It is a multifocal CNS pathology constituting two distinct clinical phases corresponding to inter-related pathological processes: focal inflammation that drives activity during the relapse-remitting stage and neurodegeneration that underlies progressive disease characterized by accumulating fixed disability. Although important advances in treatment to reduce relapse rate have been made in the past two decades, no treatments are available for patients with neurodegenerative MS. There is therefore a significant unmet clinical lacuna for the development of neuroprotective treatments. The development of new therapeutic strategies is necessary to reduce the worldwide social and economic impact of neurodegenerative diseases, which produces high rates of morbidity.

MS causes the removal of fatty myelin sheath from axons of the brain and spinal cord resulting reduced communication among nerve cells. Clinically MS is classified into: Primary progressive MS (PPMS), Relapsing remitting MS (RRMS), Secondary progressive MS (SPMS) and progressive relapsing MS. About 90% of the MS is relapsing-remitting type, which is characterized by periodic attacks (relapses), followed by partial or complete recovery (remissions).It is also common to have a progressive phase of the disease and a large study showed that around 80% of cases followed by chronic progression within 20 years. Primary progressive multiple sclerosis is the prototype neurodegenerative disease. Autoimmunity plays an important role in the disease outcome and body's own immune system attacks on the myelin sheath causing the damage. Several genetic factors including HLA-DR15, HLA-A*02 and HLA-DRB1*1501 are documented to relate with MS. So during inflammatory stage, the immune system gets activated and nerves get demyelinated while during remission stage, immune attack subsides, and the resident oligiodendrocytes remyelinate. There is also evidence of cerebral flow insufficiency into the gray matter in MS suggesting harbinger of neurodegeneration.

The registered clinical studies we are conducting are designed to provide us with a large amount of rigorously collected data so that we can better understand the clinical benefit of patients treated with stem cells.
The following clinical studies are registered through The National Institutes of Health:

1. A Study of Allogenic Human UC-MSC and Liberation Therapy (When Associated With CCSVI) in Patients with RRMS

2. A Study of Autologous Bone Marrow-Derived Mononuclear Stem Cells (BM-MNC) and Liberation Therapy (When Associated With CCSVI) in Patients with RRMS

Nervous system has limited regenerative potential. Stem cells derived from adult source, as well as placental tissues have been successfully probed to generate tissues of the nervous system during disease conditions. The rationale for use of adult stem cells as a treatment for neurological diseases such as multiple sclerosis arose from the hope that they had the capacity to foster repair of the CNS through tissue integration and differentiation into neural cells. Mesenchymal stromal cells (MSCs) are multi-potent cells that have the capability of differentiating into adipogenic, osteogenic, chondrogenic and neural cells. With these multiple capabilities, MSCs have been highly regarded as an effective transplantable cell source for regenerative medicine. Evidence from preclinical studies suggested that mesenchymal stem cells (MSCs), a subset of adult progenitor cells, are an effective therapy in preclinical animal models of neurological diseases such as experimental autoimmune encephalomyelitis, a model for multiple sclerosis, and stroke. In experimental autoimmune encephalomyelitis, intravenous injection of MSCs ameliorates clinical course and decreases demyelination, immune infiltrates, and axonal loss. Surprisingly, these effects do not require full CNS engraftment by MSCs, but rely on the capacity of MSCs to inhibit pathogenic immune responses and release neuroprotective and pro-oligodendrogenic molecules favouring tissue repair. These results led to the conclusion that therapeutic use of MSCs should initially focus on individuals with multiple sclerosis and persistent inflammation. Small clinical studies in different neurological diseases have suggested that MSCs are safe.

In our present study, we want to evaluate the safety and efficacy of autologous bone marrow derived stem cells or allogeneic mesenchymal stem cells after super selective intravenous and intrathecal administration in patients with Relapsing Remitting Multiple Sclerosis.
Assessment of treatment safetywill be based on incidence of any treatment emergent/treatment associated adverse events prior to discharge and at 1, 3, 6 and 12 months post treatment.

• Clinical evaluations, including EDSS and 29-item Multiple Sclerosis Impact Scale (MSIS-29) will be performed at baseline before stem cell mobilization, prior to discharge at 1, 3, 6 and 12 months after stem cell therapy.

• The MS Functional Composite (MSFC) consists of the (a) Timed 25-Foot Walk, (b) 9 Hole Peg Test, and (c) Paced Auditory Serial Addition Test will be performed at baseline before stem cell mobilization and at 12 months after stem cell therapy.

• Gadolinium enhanced MRI scans of the brain will be performed at baseline before therapy and then 12 months after stem cell therapy. Follow-up scans will be performed on the same type of scanner used at baseline. Scans will be analyzed centrally. The ‘baseline MRI scan’ will be the reference for brain volume changes.

We will be treating your MS from either mononuclear fraction stem cells derived from the bone marrow or cord tissue derived mesenchymal stem cells. Bone marrow autologous stem cells treatment can be done either in Trinidad or India and cord tissue derived mesenchymal stem cells will be used if the treatment is planned in Trinidad.

We will be doing internal jugular catheterization and super selective intravenous injection of either bone marrow derived mononuclear cells or cord tissue derived mesenchymal stem cells along with liberation procedure (when associated with CCSVI). This dose is followed by intrathecal administration of bone marrow derived mononuclear cells or cord tissue derived mesenchymal stem cells.

The treatment length would be as follows:Two infusions, 1st would be jugular vein angioplasty along with stem cell infusion, and 2nd will be lumbar puncture infusion, 7 days apart with follow-ups of another 7 days as direct observation before the discharge.

Our staff members will follow you up in accordance to the study protocols. Each study protocol will be discussed with you. We will also collaborate with your neurologist to monitor your disease status and also provide you with assistance to conduct MRI scans in your home country. Our medical staff will be monitoring you 1,3,6 and 12 months after treatment.