Dr. Alireza Minagar on Multiple Sclerosis- Exploring Neuroinflammation and Remyelination
Multiple Sclerosis is a neurodegenerative disorder that affects over one million individuals in the USA alone. Thanks to newer modalities and improved technology, more patients are being accurately diagnosed, with the MS society estimating 200 new diagnoses weekly. Dr. Alireza Minagar claims that extensive research has gone into understanding the immune mediated aspect of the disorder; however, neurodegeneration and remyelination being heavily overlooked. Dr. Alireza Minagar’s works in Shreveport, Louisiana have reflected these studies at work.
As a board-certified Neurologist specializing in Multiple Sclerosis and Neuroimmunology, Dr. Minagar has helped publish hundreds of research articles, and has written and edited multiple textbooks including, Multiple Sclerosis: A Mechanistic View, and Neuroinflammation. In these works, he takes an in-depth look at the pathophysiology behind MS and other neuroinflammatory disorders, and helps readers gain a more sufficient understanding of the processes involved and hopes to bring to light the many novel treatment options that could be available.
Multiple Sclerosis is defined as an autoimmune and neurodegenerative disorder in which the body’s immune system attacks the central nervous system (brain, spinal cord, and optic nerves).
The disease attacks myelin- white matter that helps insulate nerves. As a result, the usual flow of nerve impulses along nerve fibers are interrupted or distorted.
Demyelination and inflammation caused by the immune system can lead to neuronal degeneration. Symptoms vary from individual to individual; however, common signs include numbness or weakness in the limbs, typically occurring on one side of the body, tremors, and a lack of coordination. Individuals diagnosed with MS also have an increased chance of developing optic neuritis (ON) which can lead to eventual blindness.
MS is generally diagnosed further down its course as many patients present non-specific symptoms initially. They are later diagnosed by MRI where white matter lesions will be seen in the brain, or in the spinal cord. Dr. Alireza Minagar believes that while immune mediated treatments have been the mainstay of MS management. Research in remyelination and neuroregeneration will give novel treatment options to patients that may be equally, if not more effective.
Dr. Alireza Minagar comments that while the exact cause of MS is not known, it is caused by various genetic and environmental factors, ultimately dependent on neuroinflammation and neurodegeneration. The underlying pathophysiology of MS he explains is due to the activation of a patients immune system against the central nervous system and its own antigens (autoantigens), that causes a breakdown of the blood brain barrier to leukocytes and allows for them to attack the CNS.
He explains that the inciting factor for this cascade is also unknown but thought to be due to exposure or infection with viruses that carry antigens similar to those found in myelin, in what is called the molecular mimicry hypothesis. Once the autoreactive T-lymphocytes pass through the blood-brain-barrier, it is thought that further recruitment of inflammatory cytokines/markers occurs as more antigens are identified in the nervous system. IL-17, a proinflammatory cytokine, has been researched for its role in inflammation, and it has been found that immunosuppressive therapy, such as the use of INF-beta, has helped to reduce the levels of these inflammatory cytokines, helping prevent clinical features of MS.
One of the hallmarks of MS is demyelination that is caused by the immune system, and it is also the cause of progressive axonal injury, which eventually leads to long-term disability. Remyelination on the other hand is the repair of myelin, and it is thought that if therapeutic research is done on supporting this endogenous repair system, or mimicking remyelination, a significant number of patients with MS could be helped.
Remyelination is not something new but is rather a natural process that occurs during or after myelin sheath damage, and it has been found that it occurs in a similar manner to regular physiological development, but unfortunately, research is lacking into why this process fails in those with MS. Dr. Alireza Minagar has postulated that growth factors such as PDGF and EGF along with neurotrophins such as NT-3 and NRG1 drive the differentiation of progenitor stem cells into oligodendrocytes, especially in areas that are myelin deficient.
As new research regarding remyelination and neuroinflammation comes to light, researchers work hard to use this information to create new therapeutic options. For example, cell-based therapy that would supply exogenous support for remyelination, allow for the neutralization of differentiation inhibitors, or directly support endogenous remyelination and oligodendrogenesis.
Dr. Alireza Minagar has looked into novel therapies that are being researched in this field and has found that many existing drugs are being looked at to be repurposed to be used for myelin repair, such as clemastine, benztropine, and quetiapine, an H1 receptor block, muscarinic receptor antagonist, and neuroleptic respectively. Teriflunomide which is currently used as an immunomodulatory drug, has also been looked at for its use in promoting oligodendrocyte progenitor cell (OPC) differentiation.
Anti-LINGO1 is another novel drug treatment that is aimed at antagonizes and down regulates LINGO1, a transmembrane protein that has been found to negatively impact the natural remyelination process, while recently an OPC surface receptor, M3R has been looked at as it has been found to cause delayed differentiation of OPCs and inhibiting remyelination. With increased research, Dr. Alireza Minagar hopes that more novel treatment options will become available in the future in the hopes of decreasing the number of people suffering from MS.