2 Burst results for "Predisposition Syndrome"
"predisposition syndrome" Discussed on The Readout Loud
"Two thousand eighteen and a refocusing attention on whether there's a causal link with bluebirds gene therapy while bluebird investigates there's rising concern that these cancer cases could have a broader impact across the gene therapy field. We're going to discuss some of the implications of that and one under appreciated aspect of gene therapy with an expert later on in the show but before we do adam. Can you tell us what we know. So far about any link between bluebirds gene therapy and these cases of cancer. Yeah you know. We don't have much definitive information right now. Because bluebird has only learned about the two new cancer cases and is still investigating them. But here's what we do know. So one person who received bluebirds gene therapy five years ago and again. This person received that gene therapy because he had sickle cell disease up but that patient was recently diagnosed with a form of leukemia. Now the second case involved a person who received bluebird therapy more recently but then rather quickly was diagnosed with mild as plastic syndrome or md s. And that's a cancer like disease. That could also progress to leukemia now. According to bloomberg there is no definitive evidence collected yet which points to its gene therapy as the cause of these cancers but at the same time the company can't disprove that link So now it's clinical. Trials have been suspended so maybe just step back for a moment and explain at least theoretically how gene therapy might cause cancer so let's step back even further and kind of go over what gene therapy is right. Gene therapy is a procedure in which a damaged disease causing gene is replaced with a healthy gene. That functioned normally now to do that. They use viruses. These viruses are engineered to be harmless. And they're used to deliver the healthy genetic material inpatients because viruses are very adept at infiltrating cells. Now however if that virus shuttles that genetic material into the wrong place. On a patient's chromosomes it could for instance switch on cancer causing gene or it could disable a gene that prevents cells from turning into cancer so the cancer risk associated with gene. Therapy is really small but still it's enough that companies put in place safety checks to make sure that these viruses don't miss the liver that genetic payload and still the these safeguards how are like. They're just not foolproof. So figuring out the root cause of these cancer cases we talked about is obviously deeply important. For bluebird in the short term but as mentioned earlier there are potential repercussions for the entire gene. Therapy field right. Yeah that's damian. So this bluebird gene therapy uses a particular type of viruses called a lengthy virus to deliver those healthy genes into patients. Now lentiviruses are particularly adept at integrating into the genome of target cells. Which makes them effective delivery vehicles for gene therapies that target cells that divide or turnover rapidly. So that's true with sickle cell disease for instance which involves red blood cells Now if these lundy viruses are found to carry an unacceptably high cancer risk you know. That's obviously a big problem. For bluebird but also for a host of the other companies that are developing gene. Therapies that utilize lenny viruses as delivery vehicles. So we should note that. It's entirely possible that these cases of cancer have nothing to do with the lenghty virus component of bluebirds gene therapy. And a rather stu random chance however it's also possible that the culprit is a decades old. Chemotherapy called butyl fan. That is used to prepare patients. For gene therapy. This is one of the more underappreciated in less discuss aspects of gene therapy so to help us understand what's going on with the situation. We're joined by dr shave. Sharma a bone marrow transplant expert at saint jude children's research hospital. Welcome to the podcast. Thank you so much damian and thank you for the opportunity to speak to all of you today. we'll maybe let's start with your thoughts on kind of the situation overall. When you saw the news what do you think might be going on. Here honestly was a shock to many in the community both providers what taking care of patients as well as the patients Off spectacle cell disease. Something that we all need to be aware of and should be obviously looking out for is that there may be multiple mechanisms which are involved are multiple risk factors which may be involved. I am aware that many in the field and lay public are definitely concerned that this could be related to lend viral vectors as we just talked about that is obviously a factor that is under investigation and a point of concern but lengthy viral vectors. Not unique to sickle cell gene therapy lengthy viral vectors off. Some kind have been used in over ma many hundred patients so far for multiple diseases. So that's one aspect that needs to be investigated but many people don't know that sickle cell disease by itself is a myeloid leukemia. predisposition syndrome. There was a study published a couple of years ago from california where they found that the risk of myeloid malignancies in patients with sickle cell disease was very high in fact it was almost four times higher than the general population and patients of had severe sickle cell disease. And then of course. There is the question of exposure to milo toxic agents such as butyl fan which was discovered to be the case in the previous patient that was described almost two years ago so i wanted to zoom in on the fan aspect in particular. I think people might be surprised to learn that. Chemotherapy is a necessary step in the gene therapy treatment process. These patients are seeking treatment for an inherited disease like sickle cell disease. They don't have cancer. So why are they. Getting chemotherapy damian. That's a very good question in fact that's something that i'm asked all the time. When i i meet with patients who are want to undergo either transplant gene therapy. You know people normally assume that. Chemotherapy is only used to treat cancer. But that's not absolutely true. We do use milo toxic. Our agents are drugs which are which stem cells in order to create space in the bone marrow so that then we can put new stem cells. Either from somebody else as happens in the case of aboard marrow transplant or genetically modified stem cells from the patients themselves. Back into their bone marrow. So right now. Chemotherapy is an essential part of just gene therapy. But all types of transplants that we are doing for inherited disorders of the hemorrhoids system. Not just tickled disease. But palestinia certain bone marrow failure syndromes immunodeficiencies et cetera. Is there an established link between the use of fan and an increase risk with so-called secondary cancers even even years later so we know from you know giving chemotherapy to patients Over the last several years that data is a data connection of some milo toxic agents and development of second cancers down the line what i mean by second cancer as most of the times..
"predisposition syndrome" Discussed on NEJM This Week - Audio Summaries
"Eight twelve or sixteen hours was associated with a significantly greater increase in platelet function than placebo as measured by multiple as-as taika gore reversal occurred within five minutes after the initiation of PB to four five two and was sustained for more than twenty hours. There was no evidence of a rebound in platelet activity after drug sensation adverse events related to the trial. Drug were limited mainly to issues involving the infusion site in healthy volunteers, the administration of PB to four five to a specific reversal agent for Takagi lower provided immediate and sustained reversal of the anti platelet effects of tycoon. Floor as measured by multiple essays. Ms ankle moham- are Toma of the liver and Deisler one syndrome by Maria up Alana's res from the Jewish General Hospital. Montreal MS Anka moham- are Toma of the liver NHL with a reported incidence of zero point seven cases per million population per year accounts for approximately ten percent of liver tumors in persons younger than twenty one years of age, and is the second most common benign liver tumor in children after he mentio- mo- children with M H L may present with an enlarging painless abdominal mass the tumor is characterized by primitive mic sword. Stromer with cystic -ly dilated bile. Ducts alterations involving chromosome nineteen q. One three are a recurrent underlying cause of 'em H. L? These alterations activate the chromosome nineteen micro Aren a cluster. Other cases remain unexplained. These authors described to children with M H ELS that harbored germline Deisler one pathogenic variance analysis of tumor tissue from one of the children revealed to Deisler one hits mutations in Deisler. One dysregulates micro are as mimicking the effect of the activation of the chromosome nineteen micro are in a cluster. These data suggest that M H L is a new pheno type of Deisler one syndrome. Deisler one syndrome is a tumor predisposition syndrome that features several disadvantage Unedic cystic conditions in young children, most notably plural. Pulmonary blast Oma and cystic Neff froma. Chronic kidney disease of unknown cause in agricultural communities. A review article by Richard Johnson from the university of Colorado Anschutz medical campus Aurora in recent years numerous cases of chronic kidney disease have emerged among agricultural workers as well as among others performing manual labor in various regions of the world, for example, during the nineteen nineties clinicians in Central America noted that a large number of young sugar. Cane workers were presenting with end stage kidney disease and early report on an upsurge in chronic kidney disease in Central America came from El Salvador in two thousand two one striking finding was that the patients once evaluated did not have any of the conditions known to cause end stage kidney disease, spates of disease have also been identified in Sri Lanka, India and other hot reach..