Against Iron Neurotoxicity
Neurodegeneration in MS
Multiple Sclerosis (MS) is a chronic, inflammatory disease of the central nervous system where the aberrant immune system attacks the myelin and cause damage to the myelin sheath and axons. MS is also a neurodegenerative disease where prolonged and extensive damage results in the loss of axons and neurons. Neurodegeneration begins early in MS and continues with disease progression. It’s believed that progressive neurodegeneration is the primary contributor to the progression of disability in MS.
Targeting Neurodegeneration is an unmet need of MS patients
There is no cure for MS, however, there are a dozen disease-modifying therapies (DMTs) available for Relapsing Remitting MS (RRMS) and one available for Primary Progressive MS (PPMS) and Secondary Progressive MS (SPMD). DMTs work primarily on modulating the immune system to dampen inflammation. They do not directly address the neurodegeneration component of the disease. As neurodegeneration drives the progression of disabilities in MS, this explains why current medications are not effective in stopping transition into secondary progressive MS and unable to stop progression of disability. Therefore, protecting neurons against damage to prevent or slow down neuronal loss and the progression of disability are unmet needs of MS patients. This need is especially urgent for MS patients with progressive type of MS, who have limited treatment options available for them.
Iron is required for many biological processes, including the formation of myelin by oligodendrocytes. However, iron, as a transition metal, can change between ferrous and ferric forms, with a strong capacity to generate oxidative stress. Oxidative stress is a key driver of neuronal damage. In homeostasis, Iron is managed and regulated by a range of mechanisms. Inflammation alters the regulatory mechanism that keeps iron in check and exacerbates abnormal iron accumulation. If unbuffered, the extracellular ferrous iron becomes a mediator of cell injury.
Iron accumulation is detected in several brain regions of MS individuals via MRI and the histological stain. This accumulation is believed to be due to the liberation of iron from damaged, iron-rich oligodendrocytes and myelin. Abnormal iron deposition in the deep gray matter is found from the early stages of MS, including clinically isolated syndrome (CIS). Iron accumulation in the central nervous system is progressively elevated with advancing disease, is associated with the accrual of disability, and corresponds to brain areas with neuronal degeneration and demyelination.
We have extracted natural compounds from hibiscus sabdariffa (HS) with potent antioxidant and neuroprotective properties. Those compounds protected neurons against iron neurotoxicity in vitro and significantly reduced disease severity in an animal model for MS (Experimental Autoimmune Encephalomyelitis). We aim to harness the neuroprotective potential of those compounds for the development of therapeutics for neurodegenerative conditions.