Canada Talks Pharma | 084

Welcome to another episode of Biotechnology Focus radio – I am your host Michelle Currie. This week I will share with you an interesting article that I came across and then we will move on to the foremost part of the episode with Vatche Bartekian, here to tell us about his upcoming conference.      It was a work in progress, but after eight long years neuroscientists at the University of Montreal discovered a molecular mechanism that helps make sense of how Lou Gehrig’s disease, or amyotrophic lateral sclerosis (ALS), works.  This discovery could lead to a valuable new treatment in the fight to cure this crippling disease.  Amyotrophic Lateral Sclerosis is a disease that gradually paralyzes people because the brain is no longer able to communicate with the muscles of the body that we are typically able to move at will. Over time, as the muscles of the body break down, someone living with ALS will lose the ability to walk, talk, eat, swallow, and eventually breathe.  While studies such as this do not immediately give rise to new treatments for people living with ALS, they do deepen our understanding of the disease. ALS is very complicated; many cellular functions get mis-regulated. This type of work provides important information for future drug targets and the development of biomarkers aimed at detecting the disease more rapidly and following its progression.  The research began eight years ago when Jade Emmanuelle Deshaies, a research associate in neurosciences at the u of m and her supervisor, associate professor of neurosciences Christine Vande Velde, started investigating what happens to various molecules when TDP-43, a protein that binds the ‘messengers’ in the cell known collectively as RNA and that is central to ALS pathology, is removed from the nucleus.  In molecular biology, genes encode RNA and the RNA then gets translated into proteins. There are many different versions of RNA, each encoding many different versions of a protein. TDP-43, for one, binds RNA and can change how it is spliced – in a sequence of ABCD, for example, or of ABCEFG – a process called alternative splicing. Another RNA binding protein is hnRNP A1, and it gets spliced into two variants, both regulated by TDP-43. This is important because TDP-43 is known to be a major component of non-living substances in the cell called cytoplasmic inclusions that are seen in over 97 per cent of ALS cases.  The data they have show that when TDP-43 is either not there at all, or is just absent from the nucleus, you can change the splicing pattern of hnRNP A1. The big picture is that there is a much more broad spectrum of RNA metabolism mis-regulation than what was previously thought. And with that, there is more understanding of what’s going wrong, and given this new knowledge, they can potentially develop a therapy that targets this mechanism.  There is also development that parallels this research in spinal muscular atrophy (SMA) – another motor neuron disease. Scientists know that hnRNP A1 plays a role in its progress, controlling the splicing of an important gene called SMN, survival motor neuron. Vande Velde and her team don’t yet know whether or not the new splice variant they discovered changes SMN levels or function, but they point to a new drug therapy announced last year for SMA that does target the splicing of SMN by hnRNP A1.  The most amount of ALS research is done in Quebec than any other province. As Deshaies sums it up, “Science is rarely straightforward. It often takes a winding road before leading to explanations and true understanding of what we observe.”  Well that wraps up another episode of Biotechnology Focus radio. I want to thank  Vatche Bartekian again for discussing his upcoming conference with us, and thank you all for listening! From my desk to yours – this is Michelle Currie.