Iqra Mumal, MSc,  —

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.

Articles by Iqra Mumal

Anti-epileptic Keppra Could Be Candidate for Treatment of SMA, Study Finds

The anti-epileptic medicine Keppra (levetiracetam) may have a neuroprotective effect for spinal muscular atrophy (SMA), according to a recent study. The study, “The Protective Effects of Levetiracetam on a Human iPSCs‑Derived Spinal Muscular Atrophy Model,” was published in the journal Neurochemical Research. Spinal muscular atrophy (SMA) is characterized…

Motor Neuron Death in SMA Linked to Abnormal RNA Editing of 2 Proteins, Study Suggests

Motor neuron death in patients with spinal muscular atrophy is related to abnormal RNA editing of two specific proteins, which leads to the activation of a key cell death pathway and neurodegeneration, a study suggests. Genes, which are composed of DNA sequences, are transcribed into molecules called RNA. In turn, RNA molecules are used as templates to make proteins, which carry out various functions in a cell. SMA is a neurodegenerative disease characterized by widespread RNA dysfunction, leading to the abnormal production of various proteins. RNA dysfunction in SMA patients is the result of a mutation in the gene that provides instructions to make the survival motor neuron protein, which is a major regulator of RNA splicing. RNA splicing is a process by which RNA molecules are edited to produce the final RNA product. When an RNA molecule is initially made, it is composed of alternating regions known as exons or introns. Through the use of RNA splicing, the intros of the RNA molecules are cut out and the exons are joined together. These exons are a vital part of the RNA molecule that actually contain the instructions used to make the protein. A deficiency in SMN leads to significant RNA dysfunction. One of the hallmarks of SMA is the progressive loss of spinal motor neurons, and researchers have been trying to understand the cause behind the excessive death of these motor neurons in patients. Studies using mouse models of SMA have shown that motor neuron death can be attributed to the p53-dependent pathway, which is activated by high levels of a protein called p53. The role of p53 in cells is to stop them from dividing and trigger the pathways that result in cell death. The molecular mechanisms that link a deficiency in the SMN protein to p53 activation and motor neuron death in SMA are currently unknown. Normally, p53 expression is kept at low levels in the cell by Mdm2 and Mdm4, proteins that negatively regulate p53. Therefore, researchers hypothesized that p53 activation in SMA involves a dysregulation of Mdm2 and Mdm4 due to abnormal RNA splicing caused by an SMN deficiency. Using both cellular and animal models, researchers in this study showed that a deficiency in the SMN protein “disrupts the balance between inclusion and exclusion of key regulatory exons in Mdm2 and Mdm4.” Specifically, they observed that exon 3 of Mdm2 and exon 7 of Mdm4 are not included in the final RNA molecules for these proteins in SMN-deficient cells. This dysfunction in RNA splicing activity causes problems in the biological activity of Mdm2 and Mdm4, and p53 becomes active. In fact, prior studies have shown that irregular RNA splicing of these specific exons is associated with an increase in p53 activity. Therefore, researchers conclude that their findings mechanistically link dysregulation of alternative splicing induced by SMN deficiency with motor neuron death, the key hallmark of SMA.

Researchers Identify Ways to Measure SBMA Patients’ Swallowing Difficulties

Japanese researchers have identified ways to measure the swallowing difficulties of people with spinal and bulbar muscular atrophy, or SBMA. Two ways in particular could be useful in clinical trials, they said. One is the amount of swallowing residue left in the pharynx — the area in the back of the throat. Another is using the penetration–aspiration scale, which measures how far residue enters the airways and how much a person can expel back out. Hallmarks of SBMA include muscle atrophy, weakness, speech problems and dysphagia, or difficulty swallowing. SBMA progresses slowly, so it takes about 10 years for swallowing difficulties to develop. Doctors use the presence of the difficulties to predict patients' disease outcomes. But until now, there have been no reliable ways of measuring how prevalent the different kinds of swallowing problems are with these patients. Researchers at Nagoya University Graduate School of Medicine hoped to rectify this. They used X-rays to do a swallowing study in 111 SBMA patients and 53 healthy controls. The goal was to learn more about the different kinds of swallowing difficulties and possible ways to treat them that could be tested in clinical trials. The team studied patients' swallowing with a videofluoroscope. Patients drank 3 milliliters of a 40 barium sulfate solution that would show up on X-rays, revealing swallowing patterns. Researchers used videotape to record the patterns. An analysis of more than 40 patients showed three common swallowing abnormalities. One was leaving swallowing residue behind the base of the tongue. Another was residue entering the nasal passage. And still another was patients being unable to move their tongue well enough while swallowing. Another finding was that four swallowing abnormality patterns were much worse in SBMA patients than in healthy controls. One was swallowing residue entering the pharynx. Another was residue staying in the mouth. Still another was patients having to swallow several times. And the other was penetration-aspiration scores. The bottom line, researchers said, was that the most common SBMA swallowing difficulties were  impaired tongue movement and residue going into nasal passages, followed by residue in the pharynx. They concluded that residue in the pharynx and penetration–aspiration scale scores could be useful ways of measuring swallowing difficulties in clinical trials, although they noted that videofluoroscopy has limitations.