20240407 USH India Meeting Transcript

This is the full transcript for the YouTube video https://www.youtube.com/watch?v=rRXw624v4dw


[Geri speaking] All right. So we can start. My name is Geri Rosario.  I am one of three ambassadors for India of the  

Usher Syndrome Coalition. So Usher Syndrome  Coalition is an international organization  

and there are more than 2,000 members

worldwide, families with Usher individuals with Usher children, adults who are members of the  Usher syndrome Coalition. And the goal of the  

Coalition is to connect those families with Usher  syndrome with information, with researchers such  

as Dr Kumar, and with each other and with the  rest of the community. So we are very lucky to  

have Dr Kumar here. He is from the Narayan [Narayana Nethralaya].  I'm sorry I am not, I cannot pronounce  

things properly. So I will let Dr Kumar introduce  the names himself. But he is in one of the top three  

hospitals here in India, top three eye hospitals  here in India. So without further ado, I'm going  

to give it over to Dr Kumar. Oh by the way,  I'm sorry, can I request everybody to mute  

yourself. Okay if you have any questions okay  maybe we can have a break for questions. It's  

up to Dr Kumar when he wants to give a break for  questions. okay clarifying questions and then the  

rest of the questions towards the end. We have about almost a little over an hour for this  

talk but we'll definitely have question question  and answer portion. And when you do have a question,  

first please identify yourself, say your name so  that the interpreters can also identify you to  

the rest of the attendees. All right. Thank  you so much. Dr Kumar.



[Dr Kumar speaking] Okay so thank you Geri for asking me to start with  the talk and Nancy from the Usher Coalition group  

for giving me this opportunity on this  evening Indian time. I will start with my  

talk. And I will introduce myself  once I start. Let me share my screen.

I have shared my screen and also I took a  point to check if everything is okay

there. I hope my screen is visible. Everything okay Geri?



[Geri speaking] it seems to be okay. All right. [The shared screen will not appear in this video. Only interpreters will appear.]



[Dr Kumar speaking] okay  so the talk that I'm going to give is on Usher syndrome. It will be an update on the genetics,  genetic counseling and therapies. And also very  

briefly touch upon on the clinical aspect  so that everybody is on the same page.

To introduce myself, I'm Kumaramanickavel. That's a long  name so the easy way to address me is by calling  

Kumar. And I worked and studied in India.  Did my MBBS. And after which I did my MD.  

Having finished my MD, I went to New Zealand  and worked with Dr Michael John Danton  

who was the leader of the Ocular Genome  Group in the University of Otago, New Zealand . 



[Geri speaking] Excuse me. I'm sorry to interrupt. Somebody  said that the audio is low. If you can please  

speak a little louder. Thank you.



 [Dr Kumar speaking] So I went  to New Zealand and I worked with Michael John Denton and his team. And over a period of  five years, we met almost about more than a  

half a dozen genes that cause various types of vision related diseases particularly affecting

retina. And one of them is RP 65 Gene  that has come into therapy today.  

So that was identified in 1996 and published  in 1997 in Nature Genetics. And then I  

was at the National Institute National  Institute of Health Institutes of Health  

in Bethesda in the US. And I work with Fielding Hejtmancik there, the ocular genome group. And I came back to India  

worked in Shankara Nethralaya Premier Eye Hospital in  Chennai Southern India which was headed by Dr SS  

Padanath. And I set up a Genome Department there and  also a Genetic Clinic in the same hospital.  

I left that hospital 2009 to start more such genetic  clinics and genetics departments and ocular research in  

India. And then move to Naranaya Nethralaya in Bangalore  where I still work. And I also help institutions  

in Asia and collaborate with groups in   in Hong Kong , China and few other places. 

So with that introduction, let me get back to my  talk. And today I'll talk about Usher syndrome. And  

we do see many of our patients and I will  use only the term subject and not patients  

hereafter. And these subjects come to us with  various ocular related diseases and have their  

own issues for which there isn't any kind of  a medical help. So there isn't a medical help, that  

doesn't mean that they don't have any solution.  When it come to these problems that they face in  

life where we try to give solutions in genetic  counseling. So before I get to that let me move  

on with my slide and I sort of divided my talk  and structured it in such a way that I talk about  

Usher syndrome first, then genetic counseling, and  how we help people not only in Usher syndrome in  

other conditions too. And then finally I'll come  to therapies and therapies is of a very high  

importance. And therefore I have made it as a  very brief talk because it's very technical to  

be given to a very lay audience and therefore  we'll discuss a lot about therapies in the question  

session. We have many sense organs which  is a very you know lay term right from our eyes,  

skin, tongue, nose, ears, and so on and each of these  areas of sensation we have nerve endings which  

we call as receptors. And these receptors help us  to you know have the taste of hearing or vision  

touch and so on. Now these receptors  are very important and the receptors  

that we have for the eye, particularly in the  retina, is the RODS and CONES. We'll come to that

subsequently. Now eye is a very dominant source  of source of sensory perception of the external  

environment. And we can appreciate various  kinds of colors as listed in the slide over here . 

And we have very high resolution using our eyes,  576 megapixels. And our eye muscles are very active  

muscles, are very you know dynamic in nature of all  the muscles that we have in a body and we use  

this the most. Okay now if you look at the  cross-section of the eye you take an eye as a  

ball and then you try to cut it across, this is  how your eye will look like. Starts with the cornea,  

and then you have the pupilary opening and then  you have the lens. Lens and cnea are transparent.  

So the light moves from the cornea to the lens  and through the eye and hits the the most  

posterior or back end of the eyeball, and reaches  the retina. And then the retina is stimulated and  

that information goes to the brain. I'll come to  that in detail in the subsequent slides. So when  

an opthalmologist looks into your eye, I'm not an  opthalmologist, I'm a geneticist. And therefore  

when an opthalmologist looks into your eye, this is  how your retina will look like. So when you look at  

look at the retina headon, then this is how it looks  like and you can see this structure, which is   

yolk-like in appearance. And that's where the arteries  and the veins get in and get out of the eye and  

supply the nutrition and remove the toxic products  and so on, depending on whether it's the artery or  

the vein. And to the left or to your right, you  can see that you have the slightly dark red  

portion which is called as the macula and this  macula contains most of the cones and these cones  

help us to read and look at in bright light, say  for example, sunlight, daylight and also appreciate  

colors. And this these cones are present in  the center part of the retina and the remaining  

part is fully filled up with rods. Okay rods  help us to see when the light is very less  

so it is it helps us to see the contours and the  shades that are there. But they can't appreciate

color. Now if you look at cut that  retina okay and then look at the   

rods and cones, right, they will appear like this,  If you magnify that. Okay. Now if you look at the  

retina per se, it has about 10 layers and each  of them are very critical in the visual function.  

And the most important part of the retinal  layers is the sensory perception layer of rods  

and cones. So rod looks like the way as you can see  here and the the cones look like this. So because  

of the shape, they have got the names and they have  two distinctive functions as I said. Dark vision  

or less light perception is by the rods and   daylight or color vision is by the cones. And they  

are in the center part of the eye. So therefore   when you have conditions like retinitis Pigmentosa, 

the rods are the first affected and therefore  since they are present in the periphery or in  

the sides of the retina, you will start to lose the  said the peripheral vision. Whereas when the cones are  

affected, for example, in Stargardt disease, when  you have reading disabilities and you know you  

can't see images very clearly, and the central  vision is lost. And that's the distinction between  

Rod degeneration and Co degeneration. So as  I mentioned, rods help you to have this black and  

white vision, and dim light. And cons help you with color  vision or bright light. And we have about 120  

million rods and 6 to7 million cones in each eye.  So that's the accountability of these rods and

cones. Somebody has to go on mute please.  Okay. Now when the light strikes the the retina,

particularly the rods and the cones  then there is a chemical reaction that is  

immediately triggered. And it's called  as a phototransduction pathway. And that  

happens in the neuro retina. And there are a  lot of end products out of this reaction. And  

that is completely cleared by the retinal  pigment epithelium where there's another reaction  

that takes place which is called as the visual  cycle. Okay phototransduction and visual cycle.  

So therefore when photo transduction happens,  we lose lot of these chemicals and these  

chemicals are recycled in the visual cycle  by the retinal pigment epithelium and they are again  

thrown back into the retina for recycling and  reuse. Okay why am I bringing this point is  

that there are more than about 300 to 350   proteins and structural and biochemical  

proteins and each of them is represented by a  gene. Okay so Rhodopsin is one gene that is present  

in the rods which is triggered by the photon.  And similarly there are another you know 349  

genes and proteins responsible proteins which  are involved in the photo transduction and visual  

cycle pathway. So therefore the conditions that affect  the retina or the retinal pigment epithelium in  

either the photo transction pathway or the visual  cycle are not easy to be solved. And therefore the  

therapies have become a very big challenge  in the field of medicine and particularly in

opthalmology. Now the second component of usher syndrome,  the first component is the visual component of  

the condition and the second component is the  hearing. So in the hearing, in the ear we have  

three parts. One is the external ear which you  can see here as the Ear Pinna and the Ear  

Canal and then you have the Ear Drum or the  Tympanic Membrane and the Tympanic Membrane vibrates as  

I'm talking to you and you're hearing my voice  as sound. And when the Tympanic Membrane is shaking there  

are three different very small bones attached  to it and that is present in the middle ear. 

and these bone, the last bone, the third bone of  that system is again connected to the inner  

inner ear. And in the inner ear, it is connected to  a a part called as cochlea. So it starts one bone  

starts at the as I can show you in the cursor here  starts at the Tympanic Membrane or the eardrum and  

then it goes and connects to the cochlea and this is  called as the Stapes which connects to the Cochlea.  

So Cochlea is something looks the shape is almost  like a snail and it has labyrinths and it has  

a fluid and that fluid is the cochlea fluid. And when  this Stapes is moving it starts to create a  

vibration and you have sensory nerves in the  cochlea. And these nerves start to move. The receptors  

start to move when the Staples starts to shake.  Okay now as far as the retina photo receptor and  

the hearing receptor, they have certain structures  which are hairlike structures, or ciliary structures  

which they are called. And the proteins that are  there in the eye ciliary structure and the hearing  

ciliary structure are similar in nature and that  is why when you have Usher syndrome, it has about  

nearly 14 to 16 genes that are positive of Usher  syndrome. Then if one mutation happens then it  

affects the ciliary part of the photo receptor as well  as the cochlea receptor. And therefore when you have  

one gene affected it it affects two parts of the  body and therefore people with Usher Syndrome have  

both visual as well as hearing conditions. Okay  right so if you ask a common man how do we see and  

how do we hear in sense in in in terms of a sense  of perception then always everybody says that I  

see with my eye and hear with my ear. Okay  in medical terms that is not right. Okay  

in in physiological terms, the eye and the ear are  tools and so is the tongue okay and every other  

sensory organ they are all tools that we use and  that tool helps us to perceive the information and  

once the information is perceived it's sent to our  brain. and the brain tries to get that information  

and try and analyzes it and then gives it as  vision, hearing, taste, smell and so on. okay so  

the region that helps us to see is actually  the back part of the brain which is called as  

the Occipital Lobe. So that's the region which helps us  to process the information that is provided by  

the eye. And the temporal lobe which is over here is  the region that perceives information or receives  

information from the ear cochlea and then interprets  that as sound. Okay. And the whole brain there is  

an region called as general interpretation area  that connects both the vision and the hearing  

and makes us to understand things. okay for example  we see the train for the first time in life and  

our mom or dad tells us that that's the train.  and when the train makes a sound then we connect  

that sound with the train. okay the sound with  the visual perception of train and anytime we hear  

the sound alone we know that it's a train. okay so  that kind of interpretation is done by the general  

interpretation area. and so it goes with taste. any  food a smell of the food you don't need to see it  

to tell what what food it is. so therefore the  brain is the chief organ of our all perceptions.  

okay sometimes when people get injured in the  Occipital Lobe they can become blind even if the  

even if the eye is perfectly normal. okay so we now  know that why people with Usher Syndrome have both  

hearing as well as vission related problems.  okay now since I told you about 350 different  

genes are involved in photo transduction as  well as visual pathway, you can compare it with  

a car. okay so when you put your key into the car  and then you try to start the car the ignition  

starts and then you have fire that comes out of  spark plug. and then you have the gas that gets  

into the engine. and then you have combustion  and the combustion creates a pressure, moves the  

piston in the engine, and the Piston moves the  the crank shaft, and that shaft moves the tire,  

and the tire starts to move as you accelerate, and  apply for the gear or it is an automatic gear and  

so on. So the point at which you put your car key  and start and to the point where your car starts  

to run, that can be more than you know couple of  hundred reactions that take place. Each and every  

step is very important. So therefore putting in  the key is equivalent to Photon striking your  

photo receptor. And then your visual perception  at the end is sensed and similar is the cars  

moving response. So therefore if your carburetor  doesn't work in your car and reactions you know  

one you put your key and everything will start to  you know fire and move but then in the carburetor  

component which can be the 75th step doesn't work  then the whole process stops at 74 okay it doesn't  

cross that and go to 350 in the eye. So what do  you do then. Then what you have to do is that  

you have to replace that 75th Gene okay by your  gene therapy or there are other therapies. We'll  

come to this at the end of the talk. So that is how  the the scientist and doctors are trying to solve  

the genetic diseases problem. Okay they're trying tto fix so that these pathways are completed and  

therefore at the end of it, the subject is able  to have or recover or rescue with their vision  

as well as hearing. Okay. So we'll talk about  that as we come to the end of our talk now.  

I have actually completed uh talking about what  is Usher syndrome. And then I will move on to the  

next part which is genetic counseling. I'm using  some of my patients data here. I have taken  

their permission but nevertheless I have kept it  very private. I have to keep my ethics. okay  

in not trying to review too much about what I'm  talking and telling about their condition over  

in an in an open talk. I we do use this data  a little more openly without revealing people's  

privacy okay or identity in our medical talks. But I  can't do that when I'm talking to sort of an Usher  

syndrome group. okay so some of my slides are  quite concealed. but then I have to use them when  

I give a talk and somebody wants to knowmore details  I will definitely reveal it but without revealing  

the privacy of my my subjects. okay so what you  see here is that of one of my very long  

time subject who's been with me for quite long  time. and he has the condition called as Usher  

syndrome as we are talking. And his retina is  what what I'm showing here with quite a lot of

pigmentation. And his daughter also picked up  some of the information of her is also here  

in the slides. and this is a bit about their  family tree and he and his daughter are affected  

in and others are not affected in his family.  and when we ran through some of the genes  

that cause Usher syndrome in his family, we found  that he has USH2A, a gene that is having variance  

and that is causing the condition. so there are two  variants in his family. and one of the variant is  

common between him and his daughter. and the other  variant are different between the father and the  

daughter. so I'm quite trying to help him to  get into the Usher Syndrome Natural Cause of  

the Disease Trial that is going on in the US.  And he's now enrolled into it and he's  

very much on therapy because of his natural  condition or background I would say. and he's  

more concerned about his daughter. okay so when  we do this genetic counseling, it is not only that we  

are just vomiting out the genetics to them and  we end up with that. That's not the way we do it  

in India. We get very close to them and we  are very empathetic and we try to explain to  

them each and every aspect of progress of  research and what is the current status. Okay  

so we talk about the genetics so that they know  why it just happened in them. and then we talk  

about a bit on the natural cause of the condition  and how it can lead and and proceed further. And  

after which we come to the genetics part and and  so on and so forth. Next to this stage there is

a stage where people get inquisitive about  getting married. okay that's going to be the next  

subject I'm going to talk about and for one of  the reasons why they come. So in India people  

come for four reasons. okay and I'm sure that is  the condition across the world. The first reason  

I think I have to go to my next slide but and  therefore it come why they come for counseling  

in the subsequent slides. So Usher syndrome as I  told you has more than a dozen genes involved . 

And you have you know USH gene which are  of different types. Okay and USH2a is one of  

the most common condition that we see in India  okay and across the world too. There is a catch  

in this gene. It's because it's a very big gene. Okay  so therefore when people do gene therapy. Briefly  

about gene therapy is that they take the gene  of interest and they pack it inside a virus. okay  

like the way covid gets into us. So what covid does is  that it has its own genome and then it sort of  

pushes itself into our cells. And then it gets  into our genetic machinery of the cell. And then  

it starts to reproduce in that machinery okay and  multiplies itself. And then then you know we get  

affected with cpvid and then we spread with coughing  and you know breathing along with the other people  

are not affected. So the virus from us sort of gets  transferred to the next individual and keeps on   

passing over from one to another and becoming  a a pandemic okay so that's the beauty of virus . 

So it can get into our system, multiply into in  our system, reproduce, and then they can get out and  

then go ahead. So scientists captured that ability  of the virus and therefore what they did was that  

instead of their genome, they they inserted our  genome into it, our Gene of Interest into it okay,  

not the entire genome, but our gene of interest. and  then they made that Gene in in that virus to be  

reproduced and now we have say for for example  Ush2a gene that is defective being produced. We  

can produce the right copy of the USH2a inside our  own cells. It can be the the photo receptor cells  

in the retina. Or it can be the cochlea cells in the  cochlea. Okay so cochlea gene or the protein in the in  

the receptor or in the cochlea. okay so therefore  that is how gene therapy works. But again packing  

a gene of that size is not easy. okay various  other conditions of retinal degenerations like   

RP65 which causes Leber congenital amaurosis, a very severe  condition, early onset in nature which does   

make a young child to lose vision. Whereas Ushers  is a very slow one, is late in onset in terms  

of vision problems. And it's not as severe.  okay it is slow and later in onset Usher

but then Leber congenital amaurosis is much earlier. So  therefore RP65 is comparatively a smaller gene. It can  

be packed inside one virus and that can be made to  be multiplied in a laboratory and then you can  

transport that, inject it into the retina. okay sub  retinum injection as it to set. Very small volume is  

enough to have millions of viruses of our interest.  And these viruses are basically adino- associated  

virus which is a common cold kind of virus. And  they are made very safe okay before they are  

made to be infected in the retina or injected into  retina. So Usher syndrome still struggle in terms of Gene  

Therapy. and now they are doing a gene therapy   in Europe. Okay there were two groups, one of which  

was in Netherlands called ProQR. Nancy knows them  better than I do. And they have moved that study  

which is an Exon Skipping Study. I'll tell you what  that is. And then another company called Stephen Bio  (??)

is now has now taken it over. So what they did was  that so when a gene, if you say a gene, the exact  

way to explain what a gene is is like having a  train with many compartments. okay that's that's  

how a gene is. And these compartments which we call  as exons are amino acids. And then from that exons'  

amino acid, we get the whole protein. So it can be  a redoxon protein. It can be insulin or it can be  

estrogen. Or it can be growth hormone. Okay so that  is how they are produced. So they are basically  

genes DNA which is translated into, sorry  transcribed into mRNA. okay a copy that comes from  

the nucleus into the cytoplasm of the cell. And  it's a transcribed copy. It's from a DNA to RNA.  

And this RNA is translated into a protein  as amino acids. Okay and they get out of the  

cell and do do the function or they could do  the function within the same tissue. Okay so  

these are like compartments and you can have  a wrong DNA copy in one of the compartment.  

The compartments are about 100 in in nature.  You can have the 15th compartment a mistake.  

Okay now in Exon Skipping, what they do is that  if you have a mistake in the 15th compartment  

they look at it in such a way that from the  14th compartment, instead of going to the 15th  

they jump straight to the 16th. okay so they make  a protein without that 14th compartment but still  

that protein will be fairly functional. That is  Exon skipping and this is something that ProQR  

has been doing in Usher syndrome particularly  in USH2a. And I think the pandemic came and  

created quite a lot of hardship and this  now is taken over by a French company called Sephen  

Bio (??). So therefore gene therapy is fairly a  successful way of treating people with genetic  

conditions. I'll come to that at the end of my  talk. I'll show your video to believe that okay  

of gene therapy. Now this is a slide showing that  in Usher syndrome this is the eye. And then you  

know the photo receptors are affected. and then  it's also the cochlea where you have another type of  

a cilia which is also affected. Okay now I'll go  into the genetic counseling per se of my talk.  

It's part of my title today. So patients come for  for four different reason, reasons I shown in boxes  

over here. So they come for clinical diagnosis  okay. So at times when your clinician is telling  

you to do a genetic test, you should ask why  should I do the test . Okay everybody should not  

get a genetic test done, until otherwise you fall  into these four categories as in this slide. Now  

when the clinical diagnosis is not clear say see  when you say Retinitis Pigmentosa, and when you say  

Usher syndrome. You know they don't sound the same.  okay because retinitis pigmentosa is meant also as a condition  

which affects the retina alone. But Usher syndrome  is a condition that affects not only the retina  

but also the cochlea. okay so when a condition affects  two different parts of the body, or more than two  

different parts of the body, multiple different  parts of the body then we call that a syndrome.  

Okay sometimes what can happen is the one  condition might be diagnosed because a person is  

a specialist in that okay. So somebody might have  Retinitis Pigmentosa with mild hearing difficulty and  

they can actually fairly hear and they start to  also adapt by having the ability to lip read. So  

an opthalmologist might easily miss the hearing  component and diagnose it as Retinitis Pigmentosa.  

Okay it's not uncommon to happen and can't blame  the clinician for that because in India they see  

60 patients in in one day. Okay and sometimes  more than that. Some of the senior Physicians  

so uh it is easy for them to miss such kind  of problem when when the subject is  

not telling you they have mild hearing issue. So  therefore when they do a genetic test they will  

know that it is you know USH2a or USH gene that is  causing the condition okay. And they can correct  

themselves. It's not an isolated problem but it's  a syndrome. And also knowing that what type of gene  

is affected whether it is autosomal dominant,  autosomal recessive, or X-linked recessive. They can  

predict the natural cause of the condition. Say in  autosomal recessive or X-linked recessive, the condition  

can be reiterating very quickly. So they have to be  sent for appropriate rehabilitation so that they  

able to cope with the situation much faster.  Autosomal dominant is generally much slower. Okay and  

not only that it has lot of implications about the  marriage and next child and so on. And therefore I  

move from the first box to the second box. So in  the second box, people come to us to know  

whether they can get married because they have  somebody with a genetic condition in the family.  

Or they have immediate relative like a brother  or sister affected. Will that cause any issue  

with them or they themselves might be affected and  therefore they can ask about can I get married and  

have normal children. and or they can come  and say look I I would rather prefer whom I  

should choose as my partner. Okay and and they  can be people belonging to a particular group.  

Okay or a community where a genetic condition  might be much more prevalent. Okay for example  

if you take in in the US sickle cell disease  is quite predominantly present in the American  

blacks. okay and therefore in New York it's mandatory  that they have to undergo genetic counseling  

because two people might be carriers of sickle cell  disease. And the the third reason why they  

come is that they have a previous child and or  they might have a family history and they would  

have been already married and therefore they come  for preconception counseling or prenatal genetic  

counseling. Okay so and there are many tests to be  done prenatally. And you can test them. I'll show you  

one of our patients in whom we did do prenatal  diagnosis. And the fourth reason is the the Usher  

syndrome 2A subject I showed earlier. People  come to know of research intervention , genetic

research, gene therapy, stem cell therapy, you  know for retinal implants, okay clinical trials

for a particular gene, and so on. So therefore they come  and want to know what gene it is okay.

So we clearly tell them this test will not give you any result  or benefit after knowing what Gene it is okay. So  

you know you have usher syndrome. Doing a genetic test  and knowing molecular diagnosis of which USH2a is  

not going to benefit okay. We don't do a genetic  test test to know molecularly what it is are only  

trying to recoin somebody's condition. So  otherwise the you know for the first three reasons  

when they come we straight away go ahead and do  the test okay. The fourth one we make them very  

clearly understand that it's not going to be of  any benefit doing this test because stem therapy and  

other things are not still in the pipeline of  describing practice. Okay right now let me go  

to I'm not going to go all of them I go to to the  second one straight away in a premarital situation  

I mask the slide the pedigree. So here's a girl  who you know mid 20s graduate who whose  

parents married consaguineously. They are uncle and niece which  is not uncommon in our country particularly in  

southern part of India where such blood related  marriages are not in common but that is you know  

dwindling very fast with education and knowledge  and awareness. And these parents are about  

you know close to 50 years of age. And therefore  half a century ago they got married consanguineously. And  

because of that she's affected. okay and she has  her own other sibling and affective. Now because  

she's a graduate she read somewhere and knew  that it's a genetic condition. It can recur in  

the family therefore came for counseling. We took  the pedigree. It was classical autosomal recessive  

inheritance and we told her clearly if you marry  outside your family, outside your community, then  

you your children won't be affected. But being a  graduate she put her foot down and said yes I know what  

you say but then I want to know exactly what  my Gene is and I want to know what the mutation  

is okay. So we did the test. And when we looked  at the gene we found a particular Gene which  

is a bit more common in India, to be positive  of Usher syndrome. So she had a gpr98 gene Exxon 70.  

This Exon 70 is a compartment I said where she had  a change from DNA letter C to T, glycine   

in the 4,777 region, became a termination which  means it stopped you know translating amino acid.  

And it was in two copies because her parents  were blood related. They gave the identical copy  

to her and she had Usher syndrome type 2C ___ when  classification of that variant was was pathogenic.  

And if somebody wants to know more about it, I  can I can talk in the question session what is  

pathogen or variant of unknown significance and  so on. Now so therefore it's same her pedigree  

and we told molecularly that see look you have  two copies wrong and when you get married to  

somebody who's not going to be related to you they  won't carry this copy but we'll check it before  

you you get married or after you get married. And  then we can be sure that he the other partner  

is not carrying it. And you will definitely give  one copy to the child and your partner will give  

one right copy. You give one wrong copy you'll give  one right copy. A child needs two wrong copies to  

have the condition. And therefore your child will  not be affected okay. I don't know whether she  

married or not but she was quite satisfied with  what we said okay. This was couple of years ago  

that this happened. Now this is something as solution we give  okay. Even many clinicians think that the moment  

somebody has a genetic condition that means that  you know nothing can be done. And therefore of  

course from treatment point point of view what  they say is right okay. Today there's nothing  

think that can be done. But tomorrow research  will definitely give you a a solution in terms  

of treatment. But today the genomic knowledge  can give you many solutions as I told you  

in trying to know what syndrome it is, the  first option. The second option has marriage  

options what can be the option that you  can choose okay. You have the power and think.  

You know unlike the way we do medical practice,  the the autonomy in the medical practice is with  

the medical doctor or the physician, because they  decide what test to be done, what surgery to be  

done. But in in genetic counseling, the autonomy  is with the subject and their family okay. They  

tell us what we should do as genetic counselors okay. We don't have that often use and that's how the  

guidelines are set. The American College of  Medical Genetics Guidelines and most of the other  

countries guidelines are set in such the way that in genomic practice, the autonomy is with the subject,  

in the family. Right. Now I'll move on to the  preconception and the family that we counseled. And of  

course these are not Usher syndrome okay. Previous  condition was Usher syndrome but not this one. So this was



[Geri speaking] Excuse me doctor. I'm sorry. Can we  stop for a while somewhere and have others  

asked questions? If that is possible? 



[Dr Kumar speaking] Yeah yeah  go ahead. I'm happy to stop and then you can they can ask questions and then I can continue  this again. Not an issue.



[Geri speaking] All right, because I'm I'm seeing some comments in the chat. I believe  some people were not able to follow properly.  

And also also just, okay somebody had  mentioned if if you can stop sharing the  

screen. If you don't have, if if you can  just talk through the topics because some  

people are not able to see the screen properly as  well as they're not able to see their interpreters  

properly, because the interpreters are now small sized.  



[Dr Kumar speaking] okay okay you can switch over  

that my screen to be a smaller screen and  then the Interpreter to be larger. And and I  

can take questions now. 



[Geri speaking] Unfortunately I cannot  control the size of the screen sharing.

Anybody has a comment?

Questions? If if none we might  be able to proceed. Let me a sk  

the ISL interpreters, do you need to switch?



[Interpreter  speaking] Yes now it's about 30 minutes so  we will switch. Arwa, just replace as  

a spotlight. 



[Geri speaking] Okay I will remove the spotlight from Arwa.



[Nancy speaking] And Geri, Yash, this is Nancy, Yash is is signing. It looks like he has a question okay.



[Geri speaking] Saurabh, can you see Yash?



[Interpreter speaking for Yash] So he have doubt that you have explained ____ everything but like in deaf  or in hearing.

There are some genetical issue or I want to ask that if a deaf person in a  deaf community. Okay he want to know about deaf community

and sign language like hearing  person have syndrome, Ush syndrome. You are talking  

about regarding to the hearing Community, right?  As any deaf person have faced this issue? Any deaf  person?



[Dr Kumar speaking] What issue? 



[Interpreter  speaking for Yash] Usher syndrome.



[Dr Kumar speaking] Of course actually.  It depends on where what kind of institution it is. If it's an authenic institution, people  come with vision problem. And then the hearing  

condition is diagnosed. Whereas if you're running  a hearing institute and the hearing issue is  

detected and they go to hearing institution and  then finally they know that it is Usher syndrome . 

Both ways it can happen. okay both conditions  don't happen at the same time. I've seen it with  

my subjects. So the vision problem can usually  it is later in onset. The hearing condition.



[Interpreter speaking for Yash] Okay for example in world and laboratory there  are there are a lot of ___ there are a lot of

like on visual in visual chemicals. 



[Dr Kumar speaking] You know your voice got lost in the middle. 



[Interpreter speaking] I'm audible?



[Dr Kumar speaking] yeah you're audible but your  voice got lost in the middle if you can repeat what you said that would be good.



[Interpreter speaking for Yash] okay he is asking you that how we can improve visual impairment. the basic question is how we can  improve any visual impairment in Usher syndrome.  



[Dr Kumar speaking] okay um see there are uh um visual Rehabilitation  programs. so what happens with uh visual perception  

loss is that as I was talking I was telling  there are 120 million rods and uh 6 million  

cones in each eye. So when you start to lose the  rods you start to lose the peripheral vision  

and you start to lose the uh you know Twilight  Vision or uh low light vision. okay you get into  

a movie theater you find it difficult to adapt  and get into the seat in your the row that you're  

alerted. so therefore uh um this only also  start to lose the reading ability because  

the cones also start to deteriorate so when  the cones start to deteriorate uh or when the  

rods start to reduce in your peripheral vision is  getting reduced. then when the peripheral vision is getting  

you know tubular and tubular uh they can give you  certain glasses that will help to widen that view . 

okay that's the rehabilitation when your rods  are getting lost. whereas if your cones are lost  

and your reading ability is getting lesser and lesser, they try to give you um certain lens that will  

magnify or they can use certain um say devices  that helps to magnify uh if they are reading  

a book there can be some kind of a desktop  which will magnify or it can be your mobile  

phone that can magnify the letters so that  you can actually read better. okay so that is  

they try to rehabilitate people as they slowly  start to lose the rod or the cone vision. Okay uh that's  

a field by itself and most of the eye hospitals  in India do have those services of Visual  

Rehabilitation and usually the optometrist are the  people who deal with it and there are quite good  

devices wearable devices okay which you have very  good companies across the world uh which provide  

you with certain uh wearable device that you can  wear in your spectacles and they can widen your  

vision or they can magnify uh what you're seeing  and so on. okay so I hope I have answered that

question. Okay?



[Interpreter speaking for Yash] He is asking that when we getting elder so our vision  become weak right. so I I want to ask that how is  

it possible when I am in 80s or in '90s my vision  still stay strong. I can see clearly without any  

issue. How it can be done because you know now our  lifespan become less and our vision is not good  

in 21st century. so I wanted to know that how I can  improve my vision. And in in some deaf community  

people don't know about usher syndrome  because they are just staying at home. they don't  

know about vision impairment and all. okay there  is lack of uh accessibility so how we can sort it out? 



[Dr Kumar speaking] okay uh I'm not expert uh uh in hearing  disability per se okay but I know that if you  

take 100 people with hearing disability um only a  small section of people will have usher syndrome okay  

so sensory neural loss depthness um there are more  than 100 genes responsible causing uh defects in  

the cochlea particularly okay in the the inner ear and  Usher syndrome is a very small section of that. okay  

but Usher syndrome if you take in terms of visual  conditions Usher syndrome is quite a big group  

okay and therefore if you take curing per se um  there are genes that cause only hearing disability  

and those people will never get any visual  perception loss okay so you should not get  

confused between hearing everybody who  has a hearing problem will develop usher  

syndrome that's not the case. okay so  um there are there are several genes  

that causes uh hearing problems and they  don't cause vision related issues at all

okay yes some question from Divya I think right.



[Geri speaking] hello this is Geri. I think  we've we've lost uh the ASL interpreters . Who should I 



[ASL interpreter speaking] This is the interpreter  speaking. You have not lost us. I just   need you to spotlight Diane please. 


[Geri speaking] all right  all right got it.



[Dr Kumar speaking] I think Divya started off with some question. We can probably she had. 



[Interpreter speaking for Divya] yes Divya  does have a question. we're just waiting for  

her to be able to see the interpreters in  order to ask her question. Please just hold a moment.



[Geri speaking] Diane, you are spotlighted. [Interpreter speaking for Divya] Thank you. My question is um what is the future  generation of gene therapy look like as  

what what is the plan for the future generation  of gene therapy. 



[Dr Kumar speaking] okay um I've come to the the  

component I've not yet come to the component of  gene therapy. I'll finish my talk and then talk  

about it or do you want me to talk because it's a  a little premature of at the at this point of time  

I will complete hopefully another 5 seven minutes  um and then um shall I talk about that? Or do you  

want me to talk right now? 



[Aruna speaking] uh this is Divya's Mom.  okay Dr Kumar all right the problem with your in  

no way do I mean disrespect in any way okay this  is too scientific for the for everybody. Perhaps if  

you had uh done a small like a a presentation but  a uh a less scientific presentation for everybody  

and just points. Points is what we needed at this  time. so that we can grasp what you're trying to  

tell us okay and then ask proper questions. this  is too much too scientific. 



[Dr Kumar speaking] okay um I have not  

done too many uh you know talks to people uh  with the uh condition. I've done it in India.  

um this the first time I'm doing it online. I have  kept my talk very low tech. I have not kept it very  

high tech. in fact that's how I felt. all right um  otherwise it will be uh I don't know if it be if  

we don't use the medical terms and give a talk it  will not because I've been trained in US and in  

New Zealand, I can't give a very very superficial  talk. okay uh certainly we can if you feel that  

my talk is very scientific, you can note down  points and you can ask me those questions where  

I've dealt it very scientifically. I can make  it quite simple. in fact that's why I put a car  

engine as a similar and try to explain that. 



[Aruna speaking] the  other issue that we have with this presentation  

is that there's very little contrast. I mean  even slides for the slides I'm talking about  

the slides okay. um the the the thing is for a  de blind person they cannot see what's going on  

in your presentation. it's even hard for a normal  person like myself and my husband to see what's  

going on in your presentation. 



[Dr Kumar speaking] Okay I uh because  I have used images that we generally use in  

our talks and uh to get them into a contrast and  other things only people from your group can help  

me. Otherwise I I will not be able to appreciate  that. 



[Aruna speaking] right okay i' be more than happy to help in  

any way that we can uh but right now the slide  that you are showing right now I can barely  

see it. 



[Dr Kumar speaking] I have kept it deliberately like that. I  didn't tell that because of my my subject privacy  

I'm not revealing many things. okay I have both a  moral ethical and legal implication particularly  

this is online talk okay. so therefore I masked it  deliberately which I did tell in my talk. it's very  

difficult to _____ to show that. you understand  uh because this somebody's life and I can't talk  

openly about it. this is a problem that we face  in the field of medicine okay. so when we give  

a medical talk we always keep everything open. I  understand your point right now and that has been  

done deliberately. I did talk about this to Geri  that uh I have this issue because I'm talking to  

patient group and I have to be very careful.  in in fact she wanted a copy to be circulated  

I raised my concern because it is some information  that I I cannot reveal out because of my uh ethical  

restrictions. it just have to be done to restrict the uh  information. today's 



[Aruna speaking] and I'm not asking you to  

share any patient information. that's not what I'm  asking at all. I'm just like if you're if you're  

doing a presentation you can certainly take  out the information of the patient and still  

be able to share uh relevant. 



[Dr Kumar speaking] I'll give you an  example. okay uh when I when I was working in New  

Zealand uh we had a big family uh which we used  for our study. and we took all consent everything  

and clearly told them this we used uh in our  study and then uh when we published these were  

not digital days when we published in a hard  print their family uh they I we don't know how  

but they picked it up they found it in  the journal they came and discussed it with us.  

and since then we have been jumbling the pedigrees.  okay so that is why I masked the family tree completely  

l so that uh nothing uh you can identify who  it is so I don't know if uh my own patient  

is sitting in this meeting. you understand  these are tricky things that uh we have to  

be careful in our profession uh when we do um  discuss these things and I can't discuss very  

bluntly about the condition and the situation uh  without showing the uh responsible slide okay uh  

that is why these are tricky. I do understand  your point but um we are legally informed and  

we have to be ethiically careful about how we deal  with these things. so therefore we have issues on  

our side. and it's not that we are masking these  things deliberately. you should understand that.

okay and uh there are the rules of genetics is  much more stricter than the rules that we have in  

the field of 



[Interpreter speaking for Yash] sorry to interrupt. Yash here. Yash said  that he want to log off now because he have some  

urgent work so he don't need any ISL interpreter  now so he wanted us to be log off also. 



[Dr Kumar speaking] home please  

this telling to whom? 



[Interpreter speaking] he is telling to Geri that  now I'm going to log off so uh 



[Geri speaking] this is Geri.  

Saurabh and ISL interpreters, please stay  online so that you can continue signing and  

others who want to view this recording can  still avail of the op the the information.

um I would, is that okay Saurabh and Arwa? 



[Interpreter speaking] yes he said. 



[Geri speaking]  okay okay and and also for Diane and Jennifer,  

Aruna uh I know it's difficult for  Divya and um to to see the slides right now . 

Right now I am recording such that the slides  are separate from the interpretation. So if the  

recording uh is done properly you'll be able to  view the recording with just the interpreters  

on it without the slides. so I hope that that  will be some sort of a compromise . You may  

not be able to see the slides properly right  now and the interpreters might be small but  

once I have the recording you'll be able to see  the interpreters without the slides. 



[Aruna speaking] thank you  Geri. much appreciated.



 [Geri speaking] all right. 



[Interpreter speaking for Yash] thank you so  much. 



[Geri speaking] okay Saurabh and Arwa, please uh continue  

uh interpreting and uh Dr Kumar uh uh please  continue. 



[Dr Kumar speaking] Okay so Geri what I will do right now is  

that since uh the slides aren't taking uh you  know that important role in the talk uh since  

the audience has a a vision and hearing issue I  would rather say that I will hold back my slide  

from this uh point and only give the talk. and we  can have the interpreters uh much well blown up  

so that uh it makes much good sense. Will that be  okay? do you think? 



[Interpreter speaking] Geri, Saurabh here please switch us. 

Arwa is going to interpret now. 



[Geri speaking] okay Saurabh. Yes Dr Kumar  uh yes if you can please

Dr Kumar if you can please uh unshare stop  sharing okay so now we have the interpreters  

bigger now. let before you continue let me first  spotlight the correct interpreter. okay just a

minute I'm spotlighting Arwa and I am  spotlighting uh Jennifer just a minute

all right is that better? Divya can you see

Properly?



 [Aruna speaking] yes.



 [Geri speaking] all right thank you Dr Kumar  you can continue. 



[Dr Kumar speaking] okay thank you Geri um so I  

was talking about uh the last um subject who has  Stargardt's disease and um he had reading disability and  

almost lost his um total vision. and I've seen him  from very young age uh for a couple of decades and  

he's been talking to me right from the premarital  stage onwards and now when he consulted me came  

to the preconceptional stage. so before getting  into the preconceptional stage we actually uh  

tested uh him and his wife for the ocular issue of  Stargardt's disease so he had a classical Stargardt's disease  

as described in the textbook that the cones are  completely lost and so are the rods at the end  

stage. but his wife was perfectly normal as far  as the vision is concerned and when we did counsel  

him premaritally. he is from Southern India and he chose  his partner from Northern India so therefore  

uh she was not related to his family in the first  place. she was not of his own community uh in the  

the second situation. and thirdly she was not  from the same geographical region. so he's from South  

and he she's from north of India. so we tested him  and then uh we found that uh from in genetics he  

had Gene called _____ in which two of his exons  is again a very large gene. exons 2747 there was a  

change and these ch changes were pathogenic in  nature and that was positive of the condition.  

okay so this we call as compound hetero____. now I'm  using few medical jargons here. okay I have used  

them to make others understand and not keep it  very simple at the same time not too scientific  

because you are people who could be a scientist  who could be an engineer. you could be a doctor . 

you can come up with ideas okay which we as  scientist or as doctors may not think okay. so  

your bright Idea you can discuss with a non  scientist or a doctor whom you're consulting  

and that can you know trigger and come out with  something you know novel. all right. that's the  

reason I kept my talk a little scientific in  nature. it is not just to uh use some medical  

jargons. all right so therefore he had a change in  the gene called as ABCA4 Gene which is one of  

the most common gene that causes Stargardt's  disease across the world. and so it is in India

now. we tested his wife okay and with my experience  with the family tree there was no connection  

between the uh male and the female in terms of  blood and also community and so on and with my own  

practice where we have not done genetic testing  almost 80% of my career I was very clear in my  

mind that his wife will not carry any change in  this ABCA4 gene, like her husband okay. but when  

we tested it so happened that she was carrying  a likely pathogenic variant which was a learning  

curve for me. Having been in this field of genetic  counseling for last 30 years uh I was taken aback.  

okay uh fortunately we did this test and when we  counselled um the uh affected person with Stargardt's  

disease was very clear that he wanted to test  her okay. and therefore when we tested we found  

she had a change. so now we have a situation where  the husband has two wrong copies. the wife has one  

wrong copy and she has one right copy okay. now the  options are only two. the fetus can pick either of  

one wrong copy of the father and one wrong copy  if it choses from the mother. it will be affected . 

whereas if it chooses the right copy it would not  be affected okay. there's a 50/50% chance of the  

child being affected with the same condition okay . so these are situations where not only the patient  

and the family but we as genetic counselors  also get equally tensed okay. so a prenatal  

test was done and when the prenatal test was done  fortunately the fetus picked uh the right copy  

from the mother okay. so in 15 weeks when we took  the sample by the 16th or 17th week of pregnancy  

we told that this child will not be affected.  this child is born. it's a female child about  

year and a half in the middle of pandemic it was  born. second pandemic wave. and the reason I brought  

this to discuss today is that this is one of the  solutions you can offer your patients and this was  

information in fact I gave this talk in the All  India Ophthalmic Society meeting in Culcatta last month. and  

this was well appreciated by the physicians. They  were totally unaware that we could do all this in  

India okay leave alone whether they can be done  or not. so therefore these are awareness thoughts  

that not only uh the physicians should know about  it but also public. and people who are affected  

should know so that they can talk and create  an awareness amongst their own community. now  

with that uh I come to the last part of my talk  which is the what are the types of therapies  

that people are looking at okay. now Usher syndrome  as I as I showed in one of the slide has about you  

know 16 genes that are responsible for having  Usher syndrome type 1, 2 and 3. okay now in  

uh the first Intervention which is called as DNA  interventions, you can replace the gene which is  

called a gene therapy or you can correct the DNA  letter change which is called as Gene editing or  

genome editing. and these these two techniques are  quite robustly done. and Gene replacement therapy  

is very successful as far as RP 65 is concerned.  and Usher syndrome, Stargardt's disease, ____ , various  

other conditions are already in clinical trials, if  I'm right okay. now that's about the gene therapy  

or DNA interventions which is the first uh type.  now in the second type there is something called  

as RNA interventions. again that is uh picking up  much more um speed and traction compared to DNA  

interventions because it's much more easier, less  expensive. so RNA interventions there are two types.  

one is called as Antisense Oligonucleotides Therapy and the  second one is called Translational ___ Through  

Drugs and so on. so both these techniques are uh  picking up, particularly the RNA interventions  

where they try to do what is called as RNA editing.  and that is much more effective and not too  

dangerous as the term called as the Off Target Issues  which is which is quite dangerous in in genome  

editing okay. so therefore one is DNA intervention  where we have two types - Gene replacement therapy  and

Gene editing. the second one is RNA interventions.  The main one is called as the antisense oligonucleotides   

type therapy or ASO therapy. and the next one is  called as the Cell Therapy. okay and the most   

common one used in that is the Stem Cell Therapy.  okay so in that there are different techniques  

involved where you can actually take a stem cell  from the same individual and then correct that  

with some kind of editing and put it back in the  individual. okay this is one of the safest one that  

you can do. or you can actually take a cell from  other individual and then you make it as a stem  

cell which is very oriented towards retinal cell  and then you can implant it. but then that would  

need uh imuno supression in the individual  because the cell is not of self origin. it is  

a foreign cell taken from another individual and  given into you and therefore it's equivalent to  

doing um transplant, kidney transplant or any  other liver transplante and so on. immunotherapy  

suppression um imuno supression is is mandatory in  such kind of therapy state. but again stem cell has  

not caught up at least to the best of my knowledge  like the way DNA intervention particularly gene  

therapy has caught up with. but again if you ask me  the cost and factors like that um gene therapy  

is very expensive. unaffordable in fact but um um  maybe Nancy can throw better light about it for  

an Indian audience. and stem cell therapy may be  much more cheap power uh but then still we have  

not seen it to be very useful in ophthalalmology. it's  much useful in in hematological disorders okay, at  

least that's the way the it's perceived in the  field of medicine. so that is about the therapy.  

and therefore I come to the end of my talk . I  spoke about Usher syndrome at the beginning and  

then I explained what it is in terms of uh its  effect in the retina and its effect in the cochlea. 

and then I did talk about genetic counseling  which is my field um that I work on today  

with my subjects. and in uh genetic counseling we  can help people in terms of diagnosis, or whether  

when they want to get married, when they want  to have children, or they want to know uh what  

kind of gene the condition belongs to. okay but  each time you do a genetic test doesn't mean  

it will result in a positive result. okay uh  the chances of you getting the right gene and  

the right variant will be around 60%. okay 40% of  times you'll be back to square one and therefore  

we don't recommend genetic test for everybody. so  there are therapies the very promising one is the  

DNA intervention. second RNA interventions and  early cell therapies okay. so that's how the field  

is right now. but having seen the field prepandemic  and post pandemic as somebody who's been in this  

field for more than three decades uh I can see  quite a lot of traction post pandemic. the pandemic  

did actually create a big obstacle in the field of  therapies but then um it has done good I would say.  

having gone to some other the meetings connected  with therapy uh since last two years after the  

pandemic I see that there's quite a lot of  traction in therapies. and hopefully in less  

than a decade there is you know quite a lot  of application and therapies that will uh  

be happening. again we have no idea what the  cost will be but certainly there will be uh  

sort of crossroad we have faced uh during pandemic  and a new pathway will be found or what we all  

see in this field. 



[Geri speaking] excuse me doctor. I'm sorry  to interrupt you but it's already uh at the end  

of our uh meeting time so I would like to request  you to wrap it up if possible in in a minute or so . 



[Dr Kumar speaking] I already finished. 



[Geri speaking] all right all right. um I  would like to open uh the floor to one or two  

more questions and after that. okay there's  a question. can you please share the number  

of people affected by Usher syndrome in Tamil  Nadu. that's one of the questions raised. 



[Dr Kumar speaking] well I  

have no idea either. nobody has that kind of data as  far as I know but if you ask me uh if in my own  

clinical practice uh how many Usher syndrome  do I see in a month uh compared to Retinitis  

Pigmentosa I've seen um three retinitis Pigmentosa  patients in a day when I was working in Sankara  

Nethralaya. I'll see at least one or two Usher syndrome  in a month. that's the difference in which I  

see. again these are not patients from Tamil Nadu. um  I don't think such data is ever published actually  

even for Retinitis Pigmentosa. they they would say that  it's about one in 4,000 who are infected with RP  

globally. it's a conservative estimate. but Usher syndrome  I don't think such kind of data is available for our

state. okay okay it's not a big …



 [Divya's Dad speaking] Dr Kumar this  Divya's Dad. okay is any in India anybody working  

on CRISPR Technology for Usher syndrome? 



[Dr Kumar speaking] not that  I know sir. not that I know because um CRISPR is  

basically genome editing. uh I don't think anywhere  in the world, Nancy might correct me if I'm wrong,  

anybody works with genome editing for Usher  syndrome. okay um because the problem with genome  

editing is that um it can't be, say if you take  stem cell. uh if you make stem cell then it can  

work for anybody with say Usher syndrome. okay it's  much more generic in nature but genome editing  

has to be personalized you know. I'll have a mutation  in say compartment 12. another person will have it  

in compartment 15. genome editing can't be the same  for both of us. okay it has to be personalized. and  

therefore I don't know if anybody is attempting.  I've been searching for this uh gene therapy in  

Usher syndrome quite extensively and Nancy  connected me with this uh Sepul Bio Group  (sepulbio.com).

thankful to her. um but I have I can find out and  tell you but at least uh at the clinical level I  

don't think anybody is working. I don't know in  the preclinical uh level if anyone is working  

on genome editing. but having said that genome  editing is the right way to correct uh a condition.  

because you're correcting the DNA letter and the  gene will start working. it's like putting back the  

carburetor. okay and it start the car will start  working. so um I don't know if anybody's working  

that is my I reply to you. but I can find out and  then uh inform Geri so that she can inform you.  



[Divya's Dad speaking] thank you so much. 



[Geri speaking] this is  Geri. it seems like Nancy wants to say something.  



[Dr Kumar speaking] yeah yeah sure. 



[Nancy speaking] yes first of all this is Nancy.  this is Nancy speaking. can everyone hear me? I'll  

look at the interpreters. okay they are signing  so I'm guessing that my audio is working. um Dr  

Kumar thank you so much for this uh presentation.  every time we hear more about the research I know  

for myself it sinks in a little bit more. um  I'll bring that car analogy uh around with me.  

today very helpful. um but uh there are a couple  of things. um I don't know of any uh CRISPR or  

any really large scale uh Gene Therapies that  are taking place in the community right now.  

in case individuals don't know we are having our  conference in July and our research presentations  

will be on July 20th. they will be available online.  so if anyone wants to um hear the latest updates  

on research um I'm sure Geri can send out the  link if you'd like to participate remotely and  

get those updates. uh number two uh the numbers  were asked about. uh we at the Coalition generally  

have taken estimates from researchers in various  uh countries, in various studies .and we kind of  

generously say that between one in 17,000 births  um would result in a child having Usher syndrome.  

um but again as Dr Kumar said it's really it's  really just a guess. it's just a stab in the dark  

because we don't have good numbers. and what does  help is the database that was referred to earlier  

which is called the USH Trust. U-S-H and the word  "trust". it is about a 10 question um uh survey or  

if you will, and the uh Usher syndrome Coalition  maintains basic information about individuals  

who have Usher syndrome worldwide. we have about  uh 2600 people in it right now from 74 countries.  

and this data is used when researchers ask us  if there are enough people to participate in a  

clinical trial because we do assist with  outreach and finding uh participants for  

clinical trials. so if you uh get into that uh  contact database you will be the first to know  

about research recruitment worldwide. um I just  wanted to give those two points for now thank

you. 



[Geri speaking] this is Geri. thank you Nancy. uh Lata has  her hand raised. uh and also uh I I'll  

have to say Lata that this this would be  the last question. 



[Lata speaking] can you hear me. 



[Geri speaking] yes  we can. 



[Lata speaking] okay Doctor my name is Lata. i want to have some  details about my son. he's around 50 and he has  

Ushers. and he lost his of course he is deaf. and he lost his vision almost completely around  

four years back. okay but uh since six months and  since September he's having a slight Improvement.  



[Dr Kumar speaking] improvement of vision or hearing? 



[Lata speaking] vision vision. and uh to the point that he can now recognize a  

few rupee notes. he can work on the mobile phone.  he can read the mobile phone actually messages.  

and so I just want to know whether it will  ever improve. this RP. will it ever improve? 



[Dr Kumar speaking] well  

basically um I have seen this and many people  have reported also with with our patients that  

we do see in our Clinic. uh there is always a  waxing and waning as far as vision is concerned.  

and again uh scientifically talking about it  they say that there are some growth factors  

in the retina. and therefore uh certain parts  of the retina gets revived. uh and therefore the  

photo receptors become active. um since you said  this, um you kindly I would suggest you probe more  

with your son. uh if there was any kind of  lifestyle change that he adopted. 



[Lata speaking] no absolutely  

none. absolutely none. 



[Dr Kumar speaking] you better check it out okay. 



[Lata speaking]  yes because he's living with me so  

I know that. 



[Dr Kumar speaking] it could be something with diet it  could be you know some kind of Lifestyle practice.  

waking up or going to bed. or you know walking in  the streets. and eating a particular food that is  …



[Lata speaking] no no no no nothing of that. absolutely no change. I  know that. 



[Dr Kumar speaking] no there must be something otherwise  

this won't happen Madam so can you check with him. okay it can be uh some fear that he must  

have know gotten over of and therefore um it could  be certainly something very important. because when  

you tell these things to scientist and uh patients  I mean to doctors then they can work from that. all  

right so therefore uh you know when I do have some  of my patients who have reported such things and  

I've probed into them and um you might find  something. it might be some tablet that they  

would have started or they would have stopped.  okay either one could actually result in this  

kind of change. so certainly the I have seen  some people completely losing vision one morning. they  

give me a call saying they can't see anything. and  then they regain it after a couple of days. okay  

uh these are very difficult to explain. but again  it could be something with growth factors in the  

retina and retina. but that's a good news actually. 



[Lata speaking] okay  thank you very much thank you very much. 



[Divya's Dad speaking] I just  

last question to Dr Kumar. just quick. is  L-Histidin Supplement helps for the Usher syndrome?  



[Dr Kumar speaking] I'm not sure sir. i'm uh uh I'm not sure. there are  few studies which are related to amino acid   

replacement and few drugs also uh which they  do recommend. I've seen and some clinical trials  

on the drugs are also going on with the ____ uh clinical trials um but I can find out. um  

both the questions you asked today. one is genome  editing in Usher. and I whether it's preclinical  

or self study I will let you know. and also  about this L-Histidine. okay know so that you get

feedback. 



[Geri speaking] all right this is Geri. thank you so much  Dr Kumar. uh we are 15 minutes over but uh thank  

you so much for uh all the information. I know we  struggled uh trying to understand the interpreters  

as well as the slides. but I think the question and  answer at at the end um that was that was worth it.  

uh one thing I need to mention also with uh Lata's  question about her son, uh her son had 17 years of  

treatment at Shreedareeyam as well as uh uh something  like a stem cell therapy which they thought uh did  

not work out so but that was uh a few years back.  whether that has anything to do with the sudden  

uh Improvement, even little bit of improvement  in his sight, um it it it's not clear here. but  

I just wanted to to mention that because uh as  a parent with a son with Usher I want to hear  

good news that vision can be you know improved.  but you are correct, we need to research what has  

been done to reverse this, what lifestyle changes  has been done. 



[Dr Kumar speaking] okay we will uh discuss about this  

if Madame Lata wishes along with Geri. we can follow up with that and I can interact one-on-one online  

and we can discuss because even the stem cell  therapy per se could have caused good or could  

have caused bad. and it would have waned away and the  vision could have come back. it's difficult to  

guess these things. but therefore uh uh you know  um it is something we have to discuss a lot

actually. 



[Lata speaking] excuse me yes any information I can  give you regarding Arun I can give. there's  

no problem. yes yes and I be happy to share  information and uh I think I'm hoping that  

there'll be some improvement also some more  Improvement. 



[Dr Kumar speaking] yeah I'll come back to you through   Geri. 



[Lata speaking] anytime doctor thank you very much  thank you appreciate.



 [Geri speaking] all right this is Geri. I  

will set up uh that meeting because I'm also  very interested. um yeah but uh I have to say  

that we need to end the meeting now. um I will  uh this uh talk is being recorded. I'm going to  

edit the captions and uh announce to the group  when it is available for for viewing. thank  

you so much everyone. um I have to say good  night now. bye bye bye bye thank you thank you


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