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Transcript of Ohio Gathering
Rachelle Swafford's Memorial and Brad Welling, MD, PhD Presentation at theOct 8, 2011
The content of Dr. Welling's presentation at the Ohio Gathering is a discussion for general information only
& should not be considered medical advice. Patients and families need to consult individually with qualified health care professionals
regarding their own specific treatment plans.
None of the drugs mentioned in this presentation are approved by the FDA for the treatment of NF2.
This transcript was produced from the Computer Assisted Realtime Translation (CART) and is not a verbatim record and has not been proofread. The following transcript is provided as a courtesy rough draft y Professional Reports, Inc.
Part 1: Rachelle Swafford's Memorial
Part 2: Presenter - Dr. Brad Welling
Rachelle Swafford's Memorial
Gladys Bell:
Good morning, everyone. I have never used C.A.R.T., so I am a little nervous about that. But we are here this morning for a memorial for our crew member, Rachelle Swafford. Her love of the Crew is filling this room. As well as her understanding and her appreciation of the importance of what the Crew does. The fact that we reaped strength and Encouragement. Her love is in testimony by the presence of her family here today.
You know, we have many new Crew members here. It's marvelous to see this group! We become quickly attached in this group, for those of you who are new, because when you start any relationship, you start conversation by common ground. You find what you have in common and you begin conversation, and you become truthful with one another. That deepens your relationship.
We can never say to any member of this family, Deb, Ray, Danielle, or Bryan, that we understand how they feel. No one can ever understand how one individual feels in loss. But if there is one thing that everyone in this room has in common, we understand loss. All kinds of losses. Not just life, but abilities, socialization, possessions, friends. So we in this room have a lot in common.
There's a question that's asked many times: Is your glass half empty or half full?
Today we are here not to mourn, but to celebrate the life of Rachelle Swafford. Because the spirit never dies. Her spirit is in each one of her family members. Her spirit is filling this room, and that's why we are all here.
So we are in celebration here today. And it's because of the celebration of that life and all that Rachelle meant to each and every one of us.
And my husband and I didn't know Rachelle as well as most of you in this room, but in the absence of Paul Mendelson, who was to present this memorial, we were asked to fill in. But because we are attached to the Crew, we understand. And we have become attached to this family. Whenever we suffer loss, most of the time we go home. We go to our family to restore, to heal. And we are so thankful for you being here today to help us heal. When one feels something, everyone else feels something. When you stub your toe, the rest of the body responds. My husband uses that when he is in Bible study a lot, as far as members of the body. When one member of the body hurts, the rest of the body comes to rescue. We hold it. We rest it. We come to the rescue of that body part. Thank you for coming to our rescue today to help us heal.
There is a popular poem that most of you are probably familiar with, because most of you are on the internet a lot. But I want to read a portion of this because it's so eloquently talks about what we are celebrating today. The poem was written by a woman named Linda ELLIS. And she is talking about a friend who attended a memorial service.
And as he spoke about his friend, he said, "What matters most of all was the dash between those years of birth and going home. For that dash represents all the time that she has been alive on earth. And now only those who loved her know what that little line is worth. For it matters not how much we own, the cars, the house, the cash. What matters is how we live and love, and how we spend our days. It's called The Dash."
And it's a very moving poem. But the question is, how do we spend our dash. Those of us that are here, we have an opportunity to rearrange some of the things that consists of our "dash."
Today we are celebrating the dash of Rachelle Swafford, and she is very much alive in this room today. There are a number of things that I could share. There were some things that were going to be written ` that I was going to read. But I am only going to read one. And all of you can read all of them. They will be in this room a little later on.
Something that was written regarding Rachelle: "I have never met anyone who loved the Crew more than Rachelle. She was a motivating force in keeping people interacting and involved with each other. She was also relentless in her pursuit of making sure all her Crewmates were taken care of at the Ohio Gathering. Back in 2007, we had our first themed Gathering, which was a beach tropical theme. Rachelle eagerly volunteered to put together the Saturday evening activity. I remember getting regular email updates with her planning efforts, and with gift items she had selected to distribute. But the most important thing to her was making sure everyone was included, no Crewmate was to be left behind. It was her way of giving back to the people she cared about. We miss you, girl. We miss your laughter, enthusiasm, smile. And the way you showed us how to love. And encouraged others. Your memory will always be a part of the Ohio Gathering."
There are two things we want to present this morning, and my time is almost up. But first of all, these red roses are for you, Deb. We are going to leave them there until the doctor gets finished. But we have two books that contain a lot of love from a lot of Crew members. And these are messages that were written to you and to Ray. One is for you, Deb and Ray, and one is for you Danielle and Bryan. I am going to hand them to you, but they have to stay in the room because people want to add support to it. So I am going to bring these to you. These are for you and represent lots and lots of love! You know, as we become Crew members, you never part with this company, regardless of` what happens in your family. You are always a member of the Crew. And you will never be parted from membership in the Crew.
I have a small little poem written by Helen Steiner Rice I am going to read. Then I will ask my husband to come up so we can have prayer. But the poem is called "Memories are a Treasure." And I adapted one word here so that it would be appropriate for today.
But it reads:
"Memories are a treasure. Time cannot take away. So may you be surrounded by happy ones today. May all the love and tenderness of past years well spent come back today to fill your heart with beauty and content. You know, tears are fine. They are going to come for a long, long time."
But today we celebrate the life of Rachelle Swafford, and we will forever have her spirit living in our memory. Clay?
Clay Bell:
Can we bow our heads in prayer.
Father, we thank you for the strength. We are so grateful for the price you paid to set us free. We come this morning to gather as one family to honor you and bless you, encourage and inspire each other. We ask you to give us the strength to go through what we are going through here and bring back to us the remembrance of our sister. Help us, oh, God, to strengthen each other. We thank you for this gathering this morning. We ask God to continue to guide our mind and remember the peace we had with her. Help us to continue to go on in THY name. We ask blessings upon the family and encourage their hearts and their minds, oh, God. Let them know that we lift them and are here and will always be here as a family. Thank you. We ask you in these blessings made in Jesus Christ, we pray, amen.
Gladys Bell:
We have one announcement that we need to make. There has been collected a contribution to the Children's Tumor Foundation that will be sent in Rachelle's memory in the amount of $250. Phyllis?
Presenter - Dr. Brad Welling
Introduction
Phyllis:
First of all, thank you so much for coming. We come from California, Texas, Utah, New York, Georgia. I am not going to name them all. It would take too long. Thank you for the sacrifices you made to be here, to be away from your families, the financial sacrifices. We appreciate all that. But it's a special time, and it's a special place that we are all here. You don't have to worry about, "I can't hear" or "I stumble." I fell almost twice this weekend myself. But before we start, I want to thank some people for coming. Number one, Dr. Welling. I am going to say a few personal things. He is a great man! He is dedicated to the NF2. He does drug research. He wants our lives to be better. He cares about the quality of our lives. He is a patient- oriented physician.
I will tell one story that will prove this point a million times over. I had brain surgery in January. About a month later, I developed spinal fluid. Steve called Dr. Welling. To make a long story short, Dr. Welling, he was in Phoenix at the time. They actually admitted me to the hospital. And that afternoon, Dr. Welling walks in my room. He got off the airplane, came straight to Ohio State Hospital to see me. He didn't even go home. I know some of you are patients of Dr. Welling. We all have our own stories to tell about what a great physician he is, and caring wonderful man. t's a privilege and honor that he takes care of us the way he does. Thank you so much.
Next is Andrea Crago. She is from PRI, Professional Reporters, Inc. She makes this possible for us. We all would be staring at each other, making funny faces. She brings the world of speech, so we can take advantage of the great things we will "hear" this morning.
Dr. Welling, he got back at 1 a.m. this morning from Europe. He is with us here this morning. We appreciate that. I want to thank the volunteers that helped out this weekend. It's a big event. I couldn't have done this without this person taking over and that person taking over. Thank you for all your help.
Doctor Welling:
Thank you, Phyllis, for that kind introduction. Well, with I want to thank Phyllis and Steve for inviting me again this year. It's very kind of them. And thank all of you for being here also. I consider it a great honor to be asked to speak to this group. I also want to thank Shawn who I have put on the hot seat to help with my projector. It's not able to project. Should we go back to the other screen?
So I came back late last night and went to get the projector from my office this morning, and somebody had taken it. So I don't know where my projector is. I thought I would buy one at Wal-Mart because I know they carry projectors. I went there this morning. They said, oh, we have them online but don't keep them in the store! So I got the largest monitor I could find, and this is it. So I apologize for that. I am going to use this monitor and Andrea can move to the big screen if she wants to. Can you see this all right?
I am just going to take a few minutes and first do what Phyllis asked me to do, which was to talk about some of the places that I have had a chance to see as a result of our work in NF2. And I have some slides on my little MacIntosh after-wards, if you want to see pictures. We had an international conference in Rome and also an international conference in one of the other places we visited, which is escaping me right now, in Barcelona, Spain, where we presented some of our research on NF2. I have some beautiful pictures of those places on my Mac.
And I thought I would summarize some of the things that have happened in our research in the last year. Not just in our research, but a few other people's research. And I think then we could have questions and answers a little bit. To complicate things, I have a friend's wedding this morning that I am going to. So I'll try not to spend too long. We will get right to the point here.
The Process of Research
I think that you're all painfully aware of how long it takes us as researchers to get from an idea to a treatment. We start out at this end where we do testing of cells in a petri dish. Then we move to the next stage, which is to test drugs and animals. From animals, we go to preclinical trials, which means we give the drugs to patients, if they are good in animals. When we give them to patients, we have to make sure they are safe for patients to take and make sure they can get to where the tumors are. Then if they are safe and patients can take them, then we move them into patients who have NF2.
We do small scale studies first. If they look encouraging, we do larger scale studies. Finally we get to clinical trials. Hopefully we are partnering with some of the pharmacy companies who are trying to help us in this effort, and eventually we get new treatments.
If that sounds like a long passageway, it is. I think all of you would agree it takes much longer, and it's much more difficult than we would like it to be. However, it doesn't mean we don't keep trying and we don't keep working on it. We do.
Research for NF2
The gene for NF2 was discovered in 1993. It took us 18 years, so this last year, before we actually started clinical trials. But in this past year, there are five clinical trials going on with NF2. I am sure you are aware. I know some of you have participated in some of them and are participating. That's very encouraging to me. It's taken a long time to get clinical trials, but at least now we are trying some new medical treatments for NF2.
One of the studies, which I won't talk about is Lapatnib. It's one study that we have ongoing right now. There are a couple of other drugs that I want to mention to you that are follow-up from some of the drugs we talked about before.
But just one more time line for drug development I want to show you so you won't think we are all asleep in the laboratory or in the clinic, but I won't go through this in detail.
The animal testing phase of discovering a new drug takes from 6 to 10 years. The clinical testing takes a combined average of between 5 and 7 years. So the total time for a drug to come to our minds and finally get to the patient is around 15-17 years. We are always trying to develop faster ways of testing and doing things.
One of the little mechanisms that we are using right now to try to speed up the process is to do what's called Phase 0 Trial. Which means we give patients a drug before they have surgery, and then we take out their tumors and look in the tumor and see, first of all, if it got the drug and second of all, is it having any influence on the outcome of the tumor? And that way we take a small number of patients and see if we can prove the principle that at least our drug is getting into the tumor and maybe having an effect that is beneficial.
We are in the middle of one Phase 0 study with a patent, while we are also looking at moving to a second. A new drug that's shown very good results so far.
The international conference on Vestibular Schwannomas was held this year in Los Angeles. And we were invited to have a panel of physicians who are interested in finding new treatments for Schwannomas there. We invited Dr. Blakely from Johns Hopkins to be on the panel and Dr. Plotkin to be on the panel. Most of you who follow literature know them, they are very well regarded in this area.
So the three of us gave an update on current medical treatments for NF2, and I talked mostly about two drugs that have been under development at Ohio State. I spoke to this group before about a couple of those drugs. There are certainly a number of obstacles we have to think about, challenges when thinking about drug development. First of all, even though a lot of you have NF2 friends, when we look at all the patients with NF2, we don't have large numbers of patients that can be involved in studies. It's not like Breast Cancer or Prostate Cancer. We have to choose carefully when we select drugs. Even though there are many candidate drug, most of them come from treatments of other types of Cancer. They may or may not have a profile that's acceptable for human treatment. Also we don't necessarily know that even if a drug works in a mouse, that it's going to work well in humans.
Pharmaceutical companies are cautious about investing in drugs that could only be used for NF2, because it costs them about $12 to $14 million to develop the new drug and it's only for a small group of people. So it's good in a way that many of the pathways involved in NF2 are shared with other Cancers. But the drugs that are acceptable to NF2, are drugs acceptable to people with Cancer in general.
We have to have drugs that are well tolerated. Unfortunately, there is a high rate of failure of the drugs. Even when we get one through all the steps I just mentioned, only less than 10 percent actually get approved by the FDA for the indication that they are being tested for.
So I mentioned the time requirements. It's very time consuming to get through all these processes, as far as getting through time regulations, legal agreements, and getting funding to research is difficult. We live in a very strapped economy where research funding at the NIH, in the areas where we seek funding, is less than 10% of the grants that get funded.
We need to constantly balance that commitment to safety with the patients' outcome. We have to be thoughtful about the approach we take for each drug. We need to carefully choose what end points we use.
For example, in NF2, unlike other Cancers, if we could prove that we have a drug that just stopped the tumors from growing, that would be very helpful. Most clinical trials have to show that the tumors shrink substantially in order for the FDA to approve them. In fact, one of the credible trials we are starting, we will have to likely show the tumors shrink to get the FDA to approve it.
However, I am going to argue and say, if we can just stop the tumors from growing, that would be very, very helpful. Also if we could show that it stopped the hearing loss that's associated with these tumors, that would also be very helpful.
We also need to look for a drug that has sustainability of treatment, meaning we can give it over a long period of time without adverse side effects.
And also last but not least, the cost is very prohibitive for some patients and their insurance companies. So if we could find a drug that was an acceptable cost, it would be a big advantage. That's one of the reasons I am interested in trying to find a naturally occurring compound that might be useful. We haven't found one yet, but we are working on that.
There are a number of different types of tumors that we are interested in targeting with NF2. Although I am talking mostly about Schwannomas today, I will talk a little bit about Meningiomas and other tumors associated to it. It would be great to find one drug that would target all the tumors.
The Bad News
First the bad news. You are the first group to see this, so I haven't published this yet. But we have looked at a number of different naturally-occurring elements that are being used by a number of patients with these tumors: Bio-30, Sulfolane, found in a number of vegetables, broccoli, for example; Resveratrol, and Curcumin.
When we put these drugs in purified concentrations into cell cultures against Schwannoma cells, it didn't do very well. It didn't kill the Schwannoma cells in culture at a level that we thought we could get them into the tumors. So that was looking at both Vestibular Schwannoma cells and Meningioma cells. I think it's useful to know what happened when it doesn't work as well. I don't think that these naturally-occurring elements show too much hope at this point, which is unfortunate. There are a number of others we are working on. We have 19 other naturally-occurring elements we screen. One looks like it shows some promise, and two others might have some promise. But we are still working on those.
The Good News
Now the good news. AR-42 is a drug that was developed at Ohio State. It was purchased by ARNO Therapeutics. We have shown in the preclinical trials really some encouraging findings. First let me say that this drug is also being used in another study at Ohio State, in a study that's working against Leukemias, multiple Myelomas and Lymphomas. Patients are taking AR-42 for those conditions now. The drug seems to be quite well tolerated.
Dr. Ching-Shih, synthesized this at Ohio State. It has been used in Prostate Cancer as well, but we are only studying it for our Cancers. ARNO, the drug company, is very excited about this. They are happy to see that our preclinical data is looking encouraging. This clinical trial started on our campus at Ohio State. This began last year, so it's early. We don't know how well it's working to help those Cancers. But we are also looking to get approved so we can try it in NF2 as well.
Now, this is an invivo study that I am showing a graph up here, a mouse study, where we take Schwannomas out of patients. Some of you may have donated already. We put them into our mice, and then we treat them with either no drug, or AR-42. And the blue line on the graph shows the growth of the tumors in mice that were treated with control, which is no drug. And then the black line shows the growth of the tumors that had AR-42. As you can see, there is almost no growth in those patients.
This is an MRI scan of a mouse. You have seen MRI scans of patients before. You can see the white mass is the tumor here. This upper mouse has a tumor that was not treated for 14, 25, or 33 days. And then down here is a tumor that was treated with AR-42, 14, 25, and 33 days. You can still see some tumor growth over that period of time, but much less than with the untreated.
Also as I mentioned, side effects are very important when looking at the tumors. We look at side effects in the mice, too, to see if they continue to gain weight. This graph shows a normal mouse control how they gain weight over a day-to-period. The AR-42 group takes a tiny dip at first. Right here. First couple of days they started to lose weight, and then got used to the drug, and their weight gain was similar to other mice.
So we are also, of course, interested in how this would work against meningiomas, because there are no known therapeutic effects of drugs for them. 80% of meningiomas are benign, some are malignant like Schwannomas, which is very rare. In NF2-associated meningiomas, all of them have NF2 mutations. People who don't have NF2, also have meningiomas, about half of them have NF2 mutation. We have taken cells from people with them, and some without, and some other cell Iines that have NF2 mutations. All have responded well to the AR-42. That's encouraging because a drug company would be more likely to fund this type of research if they thought it might have effectiveness against run of the mill meningiomas that are not just associated with NF2. It also gives them a bigger base of patients to test clinical trials with.
Here are some of our mice. We use a little trick when using the mice. We took a fluorescent floater gene to the NF2 gene. As the tumor grows, we can take a picture through their skin. This is a display of a mouse that was just injected at one month. You can see a tiny little bit of purple here. Two months, you could see the tumor is putting out more fluorescence. Two months, three months and four months. This is another way in a mouse we can check to see how fast the tumors are growing. The reason we use this instead of MRI scans is it's much less expensive. Even in mice, MRI's are expensive.
Study Results - AR-12 and AR-42
This is the result of our meningioma study. We treated them with two drugs. One was AR-42, and the other is AR-12, which is another drug that was developed at Ohio State. So in Line 1 is the mouse that was treated with the AR-42. You can see all the way through at prior treatment, there is a little bit of tumor starting. There is little bit of purple on each mouse. At 1 month you can see a tiny bit of tumor in the AR-42-treated mouse. The normal mouse, the mouse that was just treated with control, didn't get any drugs, in Lane 2. Let me just see if I can point out Line 2. Here you see a little tumor growing at 1 month, more tumor growth at 2 months, more at 3, 4, and 5. At 5 months the tumor that was untreated had the largest amount of growth. And the tumor that was treated with the AR-42 in Line 1 has almost no detectable growth.
The two tumors, in the mice here that were treated with AR-12, have reduced growth when compared to the control, but not as profound as it is in the group treated with AR-42. In other words, in our mice, it looks like AR-42 treats meningiomas as well as Schwannomas, which is encouraging to us.
This is the growth for Schwannoma cells. This shows that the AR-42 group are treated right along this line here, show no growth. The group treated with AR-12 shows intermediate growth. The group treated with normal diet showed the most growth over the 6-month study.
These are MRI's showing the same thing. The meningiomas are shown along here. See this white area next to the brain? This is where the meningioma is growing. And this is in the group that was treated with AR-12. This is the group treated with AR-42. So, again, you can see the cap of meningioma growth here and a little bit here.
The question is, what happens if you stop the drug after you treat them for a while, you stop the AR-42, what happens? In the short term follow-up, what we can see is that here was the tumor before. After six months of treatment, there was almost no tumor detectable. After another three months of follow-up, we can detect some growth tumor, but it's not very much, not like it was before. We are not really sure. We are still following the mice to see what they will do over the long term.
There is some evidence of suppression of growth, even after you stop the drug. Most likely what we will do in patients is that we will have a drug dose for induction, where we will try to get the tumors to stop growing or to shrink a bit. If that's effective, go to a lower dose maintenance to help continue the effect of the drug treatment.
So to summarize the zenografts, the tumors taken out of patients and put into mice. The AR-42 potentially inhibits the growth of benign meningioma Xenografts. Xenograft is taking the tumor tissue out of humans and putting them into mice. Some of you have experience with Lapatnib. I won't talk about them too much. These are studies ongoing. I don't have too many answers. Because the studies are still underway.
Collaborators
Lastly, I put up a lot of people's names here who I have to acknowledge because they have had a lot of effect on this type of research. Certainly this is not research I do all on my own. Dr. CHEN is my collaborator who worked with me about 18 years. A number of these other folks are post doctors in our labs and fellows you have met from the office. Also we have a wonderful group of researchers at Ohio State who work with us in development of these drugs.
A number of collaborators that are around the country and around the world.
It takes a lot of funding support to do these kind of studies. It's very expensive. We are grateful to the NIH who has helped support this funding, as has the Department of Defense.
Hopes
I don't know if you can see this. This is one of our little guys who has inherited the NF2 gene. Although we are slow, at least we are making progress. By the time he starts developing tumors, maybe we will have options for him to treat them. I am glad he is wearing his Buckeye hat today. I hope the Buckeyes can pull it off.
Questions
Speaker:
With the mouse Xenograft, how do you prevent rejection to a foreign tissue? Secondly, AR-42, is something that is given to them as food?
Doctor Welling:
How do you prevent the mouse from rejecting the xenograft? We have to use immunocompromised mice. They don't have active immune systems so they don't reject the tumor.
The second one is, yes, we put the AR-42 in the mouse food. We do that so they don't have to have it intravenously. They put it in the food and they eat it.
Speaker:
You talk about what happens after you stop the treatment, with the drug. Two questions: What are the side effects of AR-42 and how long can you give it?
Doctor Welling:
I don't know that answer to the second question, because we haven't gone far enough in the clinical trials to know. The side effects that are being seen in the current trials that's being used at Ohio State for leukemias and myelomas, some of the patients get a drop in their platelet count. We have to watch for that.
One mouse had a drop in the platelet count. So we have to keep an eye out for loss of platelet function. But the patients in that study have a compromised bone marrow anyway because of their leukemias or myelomas. So they are probably more prone to get a platelet problem. A few patients had a little bit of nausea, but it wasn't much. We had one other side effect recently come up. I'm not sure I know too much about this side effect yet. It just was reported in the clinical trial going on where the patient had some double vision. They also had metastatic disease to their temporal bone from the myeloma. It might be they have a disease process causing the double vision and not the drug. But I don't know yet. So we have to be careful about that.
Speaker:
Is IV therapy like Avastin?
Doctor Welling:
No, it's oral.
Speaker:
When you mentioned that to get a drug approved by the FDA, it needs to show tumor reduction, but if you get a drug that would stop tumor growth, a lot of us would be happy. Is there anything that we can do to influence FDA, or is that a lost cause?
Doctor Welling:
I think -- that's a very good question, how can you help influencing the FDA so they would recognize that stopping tumor growth is a very important element. I think that what we can do is when we submit our protocols to the FDA, that we could have a letter of support from the NF2 Crew, or the Children's Tumor Foundation, to say that's a very important landmark for this disease process. The FDA is kind of stubborn, but they are not unreasonable. And so what I hope is that even if they say to us, in order for to us approve this drug, we have to show that it shrinks the tumor, I will still be able to measure if it stops the tumor growth. If that happens, then we may be able to get the drug to patients. Ideally, it would be great if it shrinks the tumors. If we can show it stops tumor growth, that would be an important enough finding to persuade the FDA that that's helpful.
Speaker:
With meningiomas and Schwannomas, or spinal tumors, is AR-42 helping?
Doctor Welling:
The question is does AR42 have any hope of shrinking spinal tumors? I would say many spinal tumors are Schwannomas and meningiomas. I would say, yes, there is hope. Fortunately, tumors tend to be less bothersome. I don't know about spinal tumors and we haven't studied them as much, but we will do that as we move forward with drug trials. I am hopeful that they will.
Speaker:
I want to ask you about the, you mentioned in the interview about how it's promising, the Herb, Honokiol?
Doctor Welling:
We have not done any studies on Honokiol yet. Some of my friends in Korea have been testing it. The studies that I have seen on that herb from Korea are quite preliminary. But they were presented a year and a half ago in Las Vegas. I know doctors who are working on it in Korea. We hope to do some testing on that drug also in some of our mice models. But we have not done that yet. So I don't know the answer to your question.
Speaker:
One other question. I read about the research by Dr. Lee, and it inhibits the growth of Meningiomas, from broccoli. Have you heard of that?
Doctor Welling:
Yes. I have heard of the research done on Boswellia, 5-Loxin. We have not done any ourselves, and I don't know if it's been replicated by others yet. I wish I had more information on it, but I don't yet.
Steve:
How do you MRI a mouse?
Doctor Welling:
You tell them, hold still!
Steve:
Is it a special MRI machine? Or in a human machine?
Doctor Welling:
Actually, what we do, you put them into a little roll, looks like a toilet paper roll. You put the nose in there and put an anesthetic gas in the other end so they go to sleep for the MRI, and you stick them in there. It's a small animal MRI machine. That way they hold still.
Speaker:
You may have touched a little on it, the orphan drug laws, do they help get drugs on the market quicker?
Doctor Welling:
Do orphan drug laws help us in terms of research? They do. NF2 qualifies as an orphan disease. It's right on the borderline. But there are few enough NF2 patients to qualify as an orphan disease. There is a section that concentrates on orphan diseases. So they were a potential source of funding for these type of research projects we are working on. Unfortunately, they don't have a lot of money. But it is an avenue that we pursue, because orphan diseases need a little extra help.
Speaker:
With the AR-42 studies with the immune-suppressed mice, so wouldn't that compromise some of the side effects?
Doctor Welling:
That's possible. In fact, the question is, if you have an immune-suppressed mouse that has no active imune system, would that change what their side effects are with AR-42?
That's a good question. And it might. Taking that same idea one step further, we are treating patients with tumors with AR-42 and looking at their side effects and saying, are these the same side effects that patients with NF2 are going to have? We don't know. We are pretending that they are the same side effects because so far they have been not too bad. And we are hoping that the FDA will allow us to move from a phase zero study that we show the tumor gets drug concentration and then move to a phase II study where we can show its effectiveness at stopping tumor growth. They might ask us the same question, how do you know the side effects are in patients with NF2? We have only tested it in other patients. We might have to answer that question. We might have to give it with patients with NF2 to see how effective it is. So it's not a perfect model, you're right.
Speaker:
If you were to remove a meningioma from a patient at Ohio State University, are you able to apply this AR-42 to that tumor?
Doctor Welling:
The answer is yes. That's what we have been doing.
Speaker:
The human tumor?
Doctor Welling:
Yes. That's the data I showed you on the mice. They are tissues from human donors.
Speaker:
It wouldn't be a mouse a tumor?
Doctor Welling:
We have done that. We have taken meningioma cell lines and injected it in there and taken human meningiomas and put them in mice. Let me just check what time it is. How about we take two more questions. Is that okay?
Speaker:
Do you collaborate with any other doctors or hospitals like LA, Miami, New York, Houston, anywhere?
Doctor Welling:
We do. The question is do we collaborate with other centers? The current studies we are doing on Lapatnib is done with the Institute of Los Angeles, Johns Hopkins in Baltimore, and New York University in New York. And on this AR-42 clinical trial that we are proposing, we have six other centers around the country that would be involved with us. We hope to make it so the patients could get to the places more easily so they don't have to travel all the way to Columbus, Ohio, if you are from Los Angeles or someplace else.
Speaker:
You mentioned a medication called Curcumin. How present in Turmeric is it?
Doctor Welling:
That's a good question. We talked about the drug derived from Turmeric. What's the concentration or how much? One of the problems that we get into with over- the-counter type of natural aide, sometimes the concentration varies dramatically from preparation to preparation because it's not controlled by the FDA. Also, the amount that gets absorbed in the body is quite variable. Often, there are a number of human agents in the naturally occurring compound. If you take one of the agents derived from bees wax, it depends on where the bees have been, what pollens they have collected, from Brazil, China, India, they have different components. It's 100 and some odd different components in the pollen that you get. When we study the mice, we try to narrow it down to the things that are most accurate and study those. Your question is a very important one because many things that people take over the counter have quite variable concentrations of the drug in them, not just that one. The bioavailability of taking those things by mouth is reduced in a number of them. When we take the concentrated form and put it right in a petri dish with our cells, it's not very effective. That's not too encouraging for that. Last question?
Speaker:
Are tumors fed by the blood supply? Can that just be cut off and the tumor would stop growing?
Doctor Welling:
Certainly stopping the blood flow to a tumor is a good thing. In fact, that's how we think Avastin works. It's a drug that attacks blood vessels. So we think Avastin helps to cut down the blood supply of the tumor. We have seen that and a couple of you have been on it. It's been encouraging. We don't know yet the long term outcome because we don't think that kills the tumor cells necessarily. But it may slow them down or stop them from growing. Who knows, maybe it does kill some of the tumor cells. That's one pathway to attack tumors, is to try to cut off its blood supply. Actually, radiation treatment to the tumors also probably does the same thing. When we take the tumor cells and put them in the petri dish and radiate them, it takes about a 22 grade to kill the tumor cells. When we give it to patients, we give it at 12-13 grade. We are not likely killing tumor cells with radiation, but killing blood vessel- type cells to stop the tumor growth. I would love to stay and talk to you all day. But I don't w not to miss my friend's wedding. I apologize for taking so long this morning to get things set up. One last question, all right. Is there one more? Okay, good. Thank you very much for your attention! Next year, if Phyllis invites me back, I am going to show you my slides of the trip I took to the Mediterranean.
Phyllis:
Always invited! Thank you, Dr. Welling. We will see you back here at 1:00 for the movie. Thank you everyone and we'll see you again.