natural treatment for vertigo disease disease

(music) (phone rings) woman: hello? oh, hi mom. hearing, even more than seeing,connects us to others. it helps us navigate business and social pathways. so when we begin to lose our hearing, we may feel ourselves becoming isolated. (dr. hume) particularly the people that we see in our clinic, a lot of them are older people;

when they begin to lose their hearing, it really means that they have problems in interacting with their family and their friends. (dr. hume) hi, mrs. willmer, how are you? as a doctor, cliff hume treats patients with hearing loss at the university of washington medical center. he sees a lot of them. (dr. hume) there's a huge number of people. in the united states, there areprobably 25 million people

with hearing loss. most of those are adults, and obviously as you get older it becomes more and more common. as a researcher at the university of washington medical center, dr. hume looks for new and better treatments for hearing loss. (dr. hume) the technology we have now is imperfect. it doesn't recover normal hearing. hearing loss is something that affects a huge number of people. we certainly think that there'sa lot of room for improvement.

for example, hearing aids don't correct hearing as consistently as glasses correct vision. (dr. hume) as people lose their hearing, a lot of the hearing loss is caused by damage to the inner ear. so not only is the sound, for example, not loud enough; it's also distorted. and as much as hearing aids can make sound louder and have abilities to focus sound that's coming in,

and help with background noise with sophisticated filtering mechanisms and so forth, they can't really make the sound clearer. and so our hope is that a more biological approach to repairing the part of the inner ear that's damaged will eventually be a better way to recover hearing that's not only louder but clearer and reproduces the type of hearing that we associate with normal hearing. this is how hearing works.

(dr. hume) this is a model or cutaway of the human ear. and we can divide it into three different parts: we have the outer ear; the middle ear, which is kind of the space between the ear drum; and the inner ear, which is in this area in here where the hearing nerve comes in. and so if we look at it in stages, this obviously is the outside, the pinna or the auricle here; the ear canal; so the soundcomes in through the ear canal,

and this would be like a cross section through your head like that. it would come in this way. the sound then vibrates the ear drum-- and this actually comes out, you can see what the ear drum looks like. so the sound hits the eardrum and then the vibration's transmitted through the chain of the three hearing bones. and two of these are here.

the malleus is the first one--or the hammer-- is the one that's kind of imbedded in the ear drum, you can see it sort of through the ear drum here. that hooks onto the incus, or the anvil, which is this one, which has a very long kind of extension here. and then that, which would be where the inner ear sets in here, would vibrate onto the stapes bone, or the stirrup bone, as the final one which would sit right in here.

and then that sets up the fluid vibrations that stimulate those hair cells. that's kind of the process by which the sound gets to the inner ear. after the sound goes through the chain of hearing bones to the inner ear, the real work of hearing begins. the stapesvibrates the that vibrationpasses up which looks alittle like a

along the cochlea arethousands of very which arearranged in very according to thefrequency of sound high frequencysounds are at the biggest partof the cochlea, its length to thelower frequencies the nerves thatconnect to the are in themiddle of (dr. hume) when the hair cells are stimulated

by the vibration in that fluid, only the hair cells that are inthe right part of the cochlea, only the ones that respond to the correct frequency that's coming in, those stimulate the hearing nerve; goes to the central part of the hearing nerve here; and then that comes out throughthe central connection of the hearing nerve that comes out through here and then goes to the base of the brain. disease,aging,

and someantibiotics by damaging theauditory nerve, the tiny haircells of the in humans, thatprocess is but through earlier research, including work done at the university of washington medical center, we know that fish and birds do regenerate those hair cells. (dr. hume) so that was a prettyamazing discovery at that point, because until then we didn't realize that there was

potentially a model system where we could study how those hair cells might regenerate and re-form that very specific pattern of cells that's responsible for hearing,and then get connected up to the brain so that they restore hearing. the question now is, can that process be made to happen in other animals? can the hair cells of the inner ear be regenerated and reconnected to the brain

through the auditory nerve? in mammals, hair cells are formed and connected as the embryo develops, but not after birth. research on that development process, as well as on hair cell regeneration in mature birds and fish, is encouraging. (dr. hume) initially,experiments in a culture system showed that it was possible to make new hair cells in a mammalian inner ear, in a culture system.

and so that's really encouraging to us to keep following on this work. and that's the work they're conducting in dr. hume's lab. it begins with making viruses, which will be used to transform cells in the inner ear. the way to construct the viruses was developed through research in another university of washington medical center lab. viruses are an effective way to reach the cells

and deliver genetic material which will stimulate the regeneration of hair cells. (dr. hume) if we look at the sites that are damaged, with hearing loss, one of the central findings is the loss of those sensory hair cells. and so if we wanted to replace those, or regenerate those, we need a way to try and either get new cells in, new hair cells, or to make new hair cells in the location where they should be.

and then the next step would be to get them connected up to the brain. unfortunately, the ear is embedded in this dense bone, and it's not easy to get to, so that we have limited ways of getting there in a way that's very efficient. and so we've tried a number ofother ways in a culture system, again, that were not very successful. but viruses have the advantage that they can, in many situations, very efficiently transfer

genetic material into different types of cells. and we can target different types of cells, whether it's in the inner ear or other parts of the body, by modifying the virus. and depending on the type of virus, they can be modified in such a way that they are extremely safe. (debra bratt) i made some plasma dna and i'm going to digest it to see if i made the correct construct. (dr. hume) debbie's focusing on trying to do

the molecular biology, basically, in trying to construct these various viruses that we want to test. and so that involves making the dna preparations and then trying to piece together the bits that control where the viruses-- what types of cells they infect, where they make the genes we put into them, where they make these proteins. and then verifying that everything is put together

the way we want, as well as making sure that those things are safe. (ming xiao) we're going to do the transfection with different kinds of animal virus. (dr. hume) ming just started working with me recently. her main project is to kind of take these constructs that we put together that debbie's been working on and then turn those into virus. so we start off with basically

a piece of dna that's not a virus. what we have to do then is to transfer that into a system where we can actually make the virus that's infectious that we can then use to test in a culture system, or to inject into the ear and see if it recovers the kind of function that we want to test. that involves a lot of work in tissue culture, which basically means growing lines of cells

that we can use that help the virus to replicate. (dr. hume) hey, debbie, do you want to tell me how things went last week with those other clones you were working on? weekly lab meetings allow the group to share information and results, keeping everyone up to date. (dr. hume) this is great. i mean, we've been working on trying to get this to work for the past several months, and this is the first time that we've had

what look like cells that are making the virus using those more deleted adenoviruses, so... (debra bratt) that is great. (dr. hume) that's excellent. (debra bratt) now i'm going to be doing the lhx3 and the mmcp one. (dr. hume) lhx3 is one of these transcription factors that we think's important for hair cell differentiation during development, and so the whole goal

of these viruses is to try to take what we think are the components that regulatethe development of hair cells during embryogenesis, and then use those to make new hair cells in adult animals. once virus replication is successful, the next step involves combining the virus with rodent ear cells for more testing. the inner ears have to be dissected first. (dr. hume) so for our experiments,

what we use is the inner ear from a rodent. and earlier this morning, debbie started the procedure to isolate the tissue from the inner ear. and in this dish, you can see there's some fluid to keep the tissue healthy. and we have the inner ear from a number of different rodents, and the next step, really, is to try and take thatapart into the components, so we have both the nerve part of the inner ear, as well as the hair cells, and then some of the other tissues

that kind of surround the inner ear and support that environment. and so what we're using this for, really, is a system to try to develop some viral vectors for a gene therapy that we'd like to use for treatment of some types of hearing loss. what i'm doing here is taking off this coil, which you can probably see on the video there. that coil has the hair cells and what's called

the stria vascularis that basically supports the health of the tissue and maintains the chemical balance in the inner ear. this kind of a coiled piece of tissue here has the hair cells on it. so it might be a little difficult to see on there, but this very thin wispy area here has all the hair cells. and this more kind ofcloudy-looking area right here, that's actually the cell bodies

or kind of the central part of the auditory nerve. and so during normal hearing, the hair cells that are in this region on this spiral stimulate the hearing nervethat's located along the inside of the spiral of the inner ear, and then that sends an electrical signal to the brain. can you actually see, debbie? (debra bratt) yeah. (dr. hume) so did you see what i did?

(debra bratt) yeah. i saw you took it... (dr. hume) you kind of grab it and then the spiral comes off, the stria should peel off. this, you can see, has a much more uniform kind of look to it, debbie, so that's the stria. this is the spiral, and you can see it's incredibly well organized. this spiral here, right here is the base, we call the base or the high-frequency part of the inner ear,

and it's wrapped around the auditory nerve. so in terms of the dissection, if you grab the core again, or the auditory nerve itself, and pull, it just unravels. if you look at the organ of corti, or the part with the hair cells, you can see very, very small detail with the rows of hair cells, and if you get the lighting right ...yeah, it's like a mosaic.

and you also can sometimes see little remnants of the auditory nerve, of the ganglion, sitting right in here. and so if you see that, you also know you've got it. finer dissection follows, toseparate the sensory epithelium from the structural parts of the coil. what's left contains the hair cells and neurons. (dr. hume) what i'm doing here is basically doing a finer level of dissection

to remove the organ of corti, or the part of the inner ear that has the hair cells. and so we remove that, along with the neurons that go out to the hair cells. and then remove some of the other tissues that normally surround the hair cells to maintain the chemical environment; remove all that, so that we can actually put them in the culture in a more isolated system.

and then we can test a number of different things. like for example, we can test some of the viruses that we've made, to see which cell types they're able to infect, and then look at the downstream effects of that, like whether or not we can cause formation of new cells that look like hair cells. again, the central question: can hair cells regenerate in mature mammals?

and if so, will those new cells be able to function, to restore hearing in a meaningful way? the next step in dr. hume's lab is to infect the very small parts of the ear with the virus then wait to see what happens. (dr. hume) one of the viruses we're testing makes a transcription factor; that means that it regulates the expression of other genes. and so we've put the gene for that transcription factor

into a virus that also makes cells green. so what we can do is look at cells that are infected with the virus, that we canidentify because they're green, and then see whether or notmaking that transcription factor changes the type of cells that they become. and because transcription factors really act to control a whole cascade of genes, they work sort of like a molecular switch. and so what we can do is, basically,

see if we can start this process in a single cell that will make it become a hair cell. a few days later, the process continues. (dr. hume) today the next step is to try and see, did the growth factors we add, did they basically make these little processes grow out the way they were supposed to? and to test that, what we do is actually label them with antibodies.

so we have some antibodies that recognize the neurons, and we basically add the antibodies; they bind to the process of the neuron. and we wash off the excess antibody, and then we detect what those processes look like by adding a fluorescent second antibody that binds to the first one and makes sort of a sandwich. and then we can use the fluorescence microscope to actually study the, what the shape of the neurons

is in culture, and then see; did those growth factors do what we wanted them to do? images from the fluorescence microscope show the results. (dr. hume) the hair cells in this case are labeled red, with an antibody that picks up protein that's only in hair cells. and then the nuclei of all the cells that are there, we can identify where all the cells are, with this blue label.

and so each one of these blue dots is where a cell is. and then the green in this case is actually a virus. so this is an adenovirus that makes a green protein, so it's fluorescent. and so all the cells that get infected turn green, and so we can actually see that these green cells are located right next to where the red ones are. once we've identified a virus that gives us the sort of pattern of expression we want,

that targets the cells we want,then we can go on and test that in an animal, and see whether or not it actually has the property we want. again, whether it's to retarget neurons or regenerate hair cells. this process will identify a virus that targets the cells that researchers want to affect. once that's done, the virus will be tested in a rodent to see if it will actually do what is hoped for,

which is regenerate hair cells in the inner ear. (dr.hume) and so in this case, we can see that we're targeting this group of cells here, that's right next to where the hair cells are. we hope they might have the best chance to have the biological properties that normal hair cells would have. someday, that could translate into giving humans the ability to regain their hearing by regenerating their own hair cells.

the work in dr. hume's lab, like other research always relates to improving patient care. (dr. hume) there's a strongconnection between the research and the people doing clinical work. most of the people who are clinicians here at the university have strong connections, either with doing research themselves, or with collaborations with basic research scientists working on related fields.

(clinician) okay, which arm would you like this done on? that one? okay. sherry willmer experienced the benefits of earlier research at the university of washington medical center when she received a cochlear implant here. she'd had hearing problems due to otosclerosis. (dr. hume) in otosclerosis, what happens is the final one of the hearing bones in the chain, the stapes or the stirrup bone, becomes fused,

so that it no longer vibrates. and so the sound basically dead ends at the stapes bone, it doesn't make it to the inner ear. and so the first step currentlyin treating that disease is to essentially bypass the stapes bone. so part of that bone is removed, either in surgery, using a drill or a laser, and then it's bypassed using a very small piston that kind of attaches to the next bone up in the chain of the hearing bones

and in many cases restores hearing almost 100 percent. so it's extremely successful in the early stages of the disease. but in a percentage of people who even have a successful result, over the intervening years as they get older, the disease can actually involve the inner ear. (dr. hume) let's just take a look at how your implant is doing. and that's what's happened to sherry willmer.

the disease severely affected her inner ear, and she became a candidate for a cochlear implant. (dr. hume) have you been having any problems at all, in terms of pain? (sherry willmer) no, not at all. it's been really easy. a cochlear implant changes the way an ear is stimulated to hear sound. it bypasses any remaining hair cells in the inner ear, sending an electronic signal straight to the hearing nerve.

(dr. hume) and there's anelectrode array that's inserted into the cochlea, the inner ear, and that stimulates the hearing nerve directly. so it doesn't require any sound input to the ear at all; the sound is all received by an external microphone and then translated into electronicsignals by a computer, essentially, and then that sends electronic impulses to the hearing nerve that then goes up to the brain. (dr. hume) i just want to take a look

at where the incision was... the university of washington medical center has a long connection to the development of cochlear implants, includingsome of the early design work. for sherry willmer, that research is changing her life now. it's worth the trip she makes from orcas island to seattle. (sherry willmer) just two weeks ago, i was outside and i heard this sound, and i didn't know what it was,

and i kept looking around, and it was a raven making a noise in the tree. and i was so thrilled that i heard... and i saw its beak moving so i knew that that's what it was. (dr. hume) at this point, what's the most difficult situation still for you? (sherry willmer) umm, a group... over four people in a room, when they all start talking, and i pick up everything. and i'm not used to that.

(dr. hume) and how about on the phone, are you doing better on the phone? (sherry willmer) the phone is difficult, and i'm practicing with it. but that's going to take a little longer. what i'm hearing is, i hear the phone ring, but i never used to. and then also i have a tea kettle, and it whistles, and i never used to hear it.

and i love hearing things like my footsteps. that's just fun. (dr. hume) yeah. (laughs) while cochlear implants are impressive, they do have limitations. they're not the same as the ear's own biological hearing process. (dr. hume) currently, cochlear implants have a limited number of electrodes, or places that they use to stimulate the hearing nerve. and so one idea, or one limitation of that,

is that they don't really reproduce the normal situation where there may be 4,000 different hair cells aligned along the axis of the cochlea in the inner ear that stimulate the hearing nerve. so we might be able to improve that connection between the cochlear implant and the hearing nerve. and that goes back to dr. hume's research goals: to improve the interaction between ear and implant, and someday to make the implants obsolete

by enabling the human ear to re-grow its own hair cells. (dr. hume) ideally what we'd like to be able to do is to try and restore the normal components of the ear that have been affected by whatever processes caused the hearing loss. so that could be loss of the hair cells or damage to the hearing nerve. and so one of the main projectsthat we're working on is trying to find a way to replacethose damaged hair cells

with ones that function in a more normal way. for patients, the benefit is clear: being able to regain lost hearing, and to hear sounds the way everyone else does, means reconnecting to the world. and cliff hume gets to experience the connection between treating patients todayand finding cures for tomorrow. it's a big part of why he chose the university of washington medical center.

(dr. hume) i really like what i do, because you have the possibility of really getting ideas from patients about what's frustrating them and take that back to the lab, and try to think of ways that you can really address those questions on a very basic level.