Genetics & parkinson's disease: Norman Fixel Foundation

Transcriot

5 oh well uh welcome um the time to kick off 0:12 thank you for coming to my little session I've got about 40 minutes and I hope to uh to make genetics 0:18 intelligible to to everyone um it's a difficult subject to uh for most 0:25 people to get their head around because uh it's pretty esoteric and most people didn't have much of an education in it 0:31 most of the neurologists I work with don't have much of an education in it either so um so don't don't be 0:38 intimidated by that um the reasons uh for studying it and so 0:46 please come on in here that's okay 0:52 um the reasons genetics are important aren't probably the reasons that you're 0:57 thinking about you might be thinking about personalized medicine you might be thinking about 1:02 why me why did I get Parkinson's disease you might be thinking about prognosis 1:09 you know more of my life look like in 10 years time if I know about my genetic 1:15 predispositions to this disease um right now we really can't tell you 1:21 many of the answers to those questions um what's important about Denise the Parkinson's disease is is that it paves 1:29 the foundation for the future in terms of developing Therapeutics in terms of 1:34 developing medications that was slow or prevent the disease from from getting 1:41 any worse or prevent it from occurring in the first place so my uh my passion 1:47 for Parkinson's these areas to predict and prevent I've been uh working in this field it's 1:53 been very humbling and in the tonight surprise consensus is now for more than 25 years so um 2:01 in the beginning to give you some insight I'm going to take you through a little story of of a particular 2:06 uh trip that I've had the journey one of my Journeys from vacancies in the in the beginning people serve as 2:14 a waste of time there is no heritability in Parkinson's disease it's very low 2:19 um you don't see Parkinson's disease really very often from families 2:25 but nevertheless everything in biology has a genetic basis any biological organism has a genetic 2:32 blueprint of his life and it's uh 2:38 everything else in in I don't know it's it's one form of truth if you like it's it's uh it's bedrock 2:45 and upon that uh those particular discoveries you can you 2:51 can basically identify targets for uh for disease for disease intervention and 2:56 for diagnosis so I'm taking a little journey a lot of story and and tell everybody about it 3:03 on the slide is a family that I was introduced to in 1997. 3:09 I was working at Mayo Foundation at the time and um I went to see uh Manfred munter he was a 3:18 neural neurologist who's the chair of Neurology and mayor of Scottsdale and Manfred and you know I was a newbie I 3:25 was a fellow green is grass really think about what am I going to work on for the 3:30 rest of my career my background is in the genetics of complex traits so what I 3:36 do is study the genetic etiology of people who seem to have 3:41 no genetic family history I actually worked on cognitive dysfunction in the 3:46 context of trisomy 21 context of down syndrome for my thesis 3:52 it's very different I worked on statistical genetics so when I came to Mayo I was looking 3:58 around and thinking to myself I was I came there to work on Alzheimer's disease and um 4:05 and I realized that the field was very crowded there was a lot of very senior people there who are very eminent and 4:11 working on on Alzheimer's disease and there really wasn't room for me it's a um anyway I went out to Mayo Scottsdale 4:17 and I met Manfred and he introduced me to a paper that he'd been working on for the last 15 20 years on the family that 4:24 he'd been working on for like 20 30 years this life it's named after him it was named the Spellman munta Kendrick he 4:30 inherited it in a sense from his his predecessor and um 4:36 and he was writing up a paper a biochemical paper at the time on four brains four autopsies that had come from 4:42 this particular family no one had figured out what was wrong this patient 4:48 and you might notice that she has a masked face is holding the baby in a kind of strange 4:53 way she's got a little bit of kind of dystonic posturing in one arm 4:59 she came to Mayo in in 1924. she has young onset Parkinson's disease 5:06 and almost every Gene in Parkinson's disease that matters you know from a clinical trial 5:12 perspective was identified in patients with young onset Parkinson's decision 5:17 most of them we know now are for the family history of the condition that may 5:24 not be obvious it may not be immediately apparent gene mutations have to be what we call 5:29 penetrant they have to manifest and even the invitations of the penetrants have 5:36 uh well has to be greater than 50 maybe greater than 70 to be able to see it manifest in a kind of mendelian sense so 5:43 this may not make no sense you might remember Mendel and his Peas I don't know his basic genetics Mendel 5:50 came up with the idea that genetic traits can be passed down from one generation to another there's dominant 5:56 traits from recessive traits and you can see these patterns in some families but that's only for really really penetrant 6:03 causes of disease and that's incredibly rare in in most disorders let alone Parkinson's disease it's incredibly rare 6:10 to find families with PD so first question you might have you know if I have a genetic risk factor 6:16 for Parkinson's Disease what's the likelihood I'm going to pass that down to my kids and they're going to manifest the disease that's what a lot of people 6:23 have concerned about worried about um the likelihood of that is very very low very low not I wouldn't be concerned 6:31 ab