My project studies the cardiovascular abnormalities and their causes in Spinal Muscular Atrophy.
- 2019 - Present: PhD Integrative Physiology (University of Edinburgh)
- 2018 - 2019: MRes Biomedical Sciences (University of Edinburgh)
- 2015 - 2018: BSc Life Sciences (University of Mumbai)
Spinal Muscular Atrophy (SMA) is an infantile autosomal recessive motor neuron disorder caused by the deficiency of SMN protein.
Previous studies report that cardiovascular abnormalities were found to be evident in ~75% of type 1 SMA patients prior to their first sign of neuromuscular degeneration. Recently, the FDA has approved SMN enhancing therapeutics Spinraza and Zolgensma to treat SMA; however, these therapies have been aimed at improving the neuromuscular pathology, which is commonly seen in all patients as compared to the cardiac defects.
Reported cardiac defects include congenital heart defects like atrial and ventricular septal defects, hypoplastic left heart syndrome, dilated right ventricle. Structural defects like thinning of left ventricle (LV) and inter ventricular septum (IVS), vascular cardiomyopathy, fibrosis, cardiac rhythm disturbance, increased apoptosis, reduced microvasculature are reported in the disease models (Figure 1). Although ubiquitously expressed, the definitive functions of the SMN protein in the cardiac tissue and its mechanisms are still unknown. In summary, although traditionally classified as a motor neuron disease, in SMA there are also significant cardiac abnormalities. There is a wide gap in the occurrence and understanding of disease pathology in the cardiac tissue, which makes it further difficult to specify therapies for these tissues.
My project will provide new insights about the threshold requirement of SMN protein for efficient cardiac function; defects being caused due to a disturbance in the cardiac development or due to disease progression; the evolution of cardiac pathology over disease time course; the function of Smn protein in the heart; and to establish a therapeutic agent designed specifically for the recovery of the heart. With newly developing therapies and drugs, it is becoming increasingly important to study these defects and the probable outcomes if the cardiac defects are not rescued by the current approved therapeutics.