In this video, Pramod Mistry, MD, and other Yale experts explain how research into Gaucher Disease has not only improved our understanding of its mechanisms, but also led to important insights into common diseases such as cancer and neurodegenerative conditions.
gosh. A disease is a rare disease. It is due to an enzyme deficiency in the listener soames of cells which are garbage factory, if you like, that are involved in breaking down a lipid. And so if there is a deficiency of this enzyme, then the lipid builds up in the lizards soames and the cells get engorged with the lipid and these lipid filled cells which are prominently cells called the macrophages, collecting organs around the body such as the liver, the spleen, the bone marrow in the lungs and cause disease manifestations. There are two types of treatment. One is every two weeks having infusions of the enzyme. This treatment has been transformative in that it leads to extraordinary universal of disease in the liver and the spleen and the blood counts. But over time we've learned that 90% of the enzyme goes into the liver and the spleen. So other organs, if there is disease activity continue to progress despite treatment. And so this new treatment that we took a lead role in helping to develop uh and it is now approved by the FDA. It's a substrate inhibitor and it has resulted in very impressive an incremental responses compared to enzyme replacement therapy. And what we learned from that is that Gosh, a disease is more than just the macrophages. It is involving many other immune cells. And so that has led us on a path of extraordinary research where what we've learned is that this lipid is a very potent anti gin for the immune system, lipids are associated with inflammation and inflammation triggers the immune system and when the immune system is triggered and if it's triggered apparently it can give rise to all kinds of different cascades that can lead to fibrosis and cancer immune cells which interact with macrophages. Like for example take B cells or T cells. They also get affected and all of these cells if there is any dis regulation in these that can cause cancers and mostly myeloma in case of kosher disease. What we find is that if you reduce the substrate, if you reduce these lipids which are being accumulated in the kosher disease by giving substrate reduction therapy um that can actually reduce the formation of gamma apathy. What we've learned is that one third of multiple myeloma patients in the cancer center actually have the same mechanism for the development of multiple myeloma. So here is a rare disease that is illuminating a common disease. And I can tell you the same story with Parkinson disease. We are trying to see if certain lipid molecules that accumulating negotiates are actually increasing your risk for Parkinson by interacting with the protein called sina Cleon, which clumps in patients brains. So we think the lipids are triggers for cineplex clumping. The primary treatment. What caused your disease is enzyme infusions and substrate election therapy in and they cannot cross the blood brain barrier that's a major carrier right now there are clinical trials that are being held or at Yale. So these substrates can cross the blood brain barrier. What we are doing at Yale is doing whole genome sequencing in more than 500 patients with heart disease. It is the largest patient population that has ever been assembled with the horizon sequencing whole genome sequencing. You can look for this rare variants. We can really tell the potential functional relevance of each where parents. So they give us some information about the genes apart. Was involved in the culture disease ideology. In our program, we really have developed a culture of providing holistic care. So we want to provide uh science based, cutting edge therapies and apply the The most advanced technologies in the world to assess Gachet disease. But we don't want to forget that person behind it. I think that armed with the tools that we have in the 21st century, no patients should be an enigma. We should be able to get to the root cause of their ill health and fix it.
