S4, E09: SCA3: A Family Affair

Greg Klassen (00:03):
There are real people on the other end of this disease. You guys have the knowledge and the brain power that I don't have that can make these solutions, these cures possible. You're affecting real people. Go forth and make sure that your diligence cures people.

Todd Poley (00:56):
Rare disease treatment is a growing area of focus for drug developers, but currently, only 10% of these conditions have an available treatment approved by the FDA. Patients with these diseases often have cognitive or physical impairments that limit their mobility and in turn their ability to participate in clinical trials. And of the 7,000 known rare diseases in the world, 80% are genetic meaning for a subset of these patients, their conditions run in family. For those who have witnessed grandparents and parents struggle with the disease and who have children with the same condition, participation in a clinical trial may be the key to not only alleviating their suffering, but that of their loved ones as well. I'm Todd Poley, and in this episode of Vital Science, we speak with Cure Rare Disease board member Greg Klassen. Greg talks with us about his struggles with Spinocerebellar Ataxia Type 3 or SCA3, a rare inherited form of ataxia. We hear from Greg on how the disease has impacted his family, including his son, Jeff, and the novel ASO treatment that has sparked optimism for the future of SCA3.

Gina Mullane (02:07):
Welcome, Greg. We're honored to have you on Vital Science today.

Greg Klassen (02:11):
Thank you. It's an honor to be here and I'm looking forward to the interview.

Gina Mullane (02:18):
So Greg, both you and your son Jeff, are living with a rare disease known as Spinocerebeller Ataxia Type 3 or SCA3. When did you and Jeff first receive this diagnosis?

Greg Klassen (02:33):
Well, for me, I saw my great-grandmother, my grandfather walking with a cane, and then I saw my father stumbling around. I can remember him walking down on a pier with his grandson, my son, and thinking, "Oh my goodness, I hope they stay on the pier." And then years later when I was training for marathon, actually I was stumbling and I couldn't figure that out. And so for me, the diagnosis or the finding out of SCA3 was a very slow and natural process that... It was 2005 when I could, I mean in my own mind said, "Man, I must have this disease because I'm stumbling so much." I will say that Jeff's story is more dramatic. I'll leave it for him to tell that story.

Gina Mullane (03:47):
How old were you in 2003?

Greg Klassen (03:50):
I was, so let's see, about 40 some years old.

Gina Mullane (03:56):
And to have this run in your family with your grandfather, your father, yourself and your son, all affected by this disease, how has this impacted your role as a patient advocate?

Greg Klassen (04:09):
Wow, good question. To me, I mean, my son is asymptomatic. He has done the DNA testing, seeing that my sister has the disease as well. And to me, I mean they are both asymptomatic, my son and sister. And if my experience somehow can be used so that they never have to experience these symptoms. That's how it's affected me. I mean, I've just going into hyperdrive in terms of reaching out and making research possible.

Gina Mullane (05:02):
I'd love to dive into that a little bit. I know you work closely with Cure Rare Disease and we've spoken about that organization in our podcast before. I understand you are passionately leading the way toward a cure for SCA3, for your family and for the world, for everyone actually. Can you tell us about your role within that organization, Cure Rare Disease?

Greg Klassen (05:28):
Yeah, so I am both on the board of directors for Cure Rare Disease as well as the SCA3 Guinea pig. The current plans are to do an ASO injection in 2024, and I am just trying to stabilize my current position because again, ASO will just stop the disease. It doesn't change my symptoms or reverse my symptoms. But hopefully my family can benefit from that, the experience. The giving... But anyway, I'll leave it at that. Sorry.

Gina Mullane (06:28):
Yeah, no, I appreciate that. I was also wondering, do you see these efforts toward pioneering a cure for SCA3? Does it link up with any other rare diseases or is it really-

Greg Klassen (06:43):
Oh. It is very similar to Huntington's Disease in that there is what they call in the industry a CAG repeat that I'm sure all the Charles River folks will know about. Vital Science will know about, that when that repeat increases, in my case, it impacts the cerebellum. But the same disease processes present for Huntington's Disease, I think Parkinson's disease and so many other genetic diseases, I do hope that what they find in SCA3 will help those diseases as well.

Gina Mullane (07:45):
So I understand that it's a rare inherited form of ataxia that affects the central nervous system and was hoping you could tell us a little bit more about the characteristics and the symptoms of the disease so that we can understand it a little bit more?

Greg Klassen (08:03):
Yeah. So SCA3 affects the cerebellum. And the cerebellum is the coordinator of all your functions, your visual system, your vestibular system, and it comes together and controls, gait, and the fine motor skills, speech. As you can tell, my speech is somewhat distorted from the disease as well as swallowing and a whole bunch of other things like that. In addition, it affects your mood and your mood swings. One of the things that is most traumatic about this disease is the mood swings and the effects that has on your family. In my case, splintering my family, because it's hard to live with the guy that has SCA3. I can be happy. And then as my son says, I can come in a room and just kill the mood of a room by my mood all because this crazy SCA3 disease.

Gina Mullane (09:42):
That has to be challenging. And you mentioned that Jeff is asymptomatic. What is the probability that things will stay like that for him?

Greg Klassen (09:54):
I mean, almost 0%. He will... He's just doing everything he can to prevent this because this disease is not something you want to fool around with. I mean, it messes with your head and it does so many... I mean, the cerebellum is so important in controlling your and mood, your swallowing, your gait. I mean typing on a keyboard is very much cerebellar and all that. And so he's just doing what he can to keep the symptoms at bay. I mean, he fights this disease by fasting. By incredibly... I mean he does no sugar in his diet and no processed food, but he will have symptoms eventually unless there is a cure.

Todd Poley (11:14):
There are less than 50,000 people in the US living with SCA3. So far, scientists have discovered 40 different types of SCA. All types have similar causes and symptoms. With SCA3, also known as Machado-Joseph disease being the most common. Caused by an inherited gene mutation. Some types occur because a segment of DNA abnormally repeats several times. It is typically diagnosed when a patient begins exhibiting symptoms. These may include problems stumbling and other problems with balance or coordination, involuntary eye movement, slurred speech, and learning disabilities. Most SCA types can be confirmed through genetic testing. Let's hear more from Gina and Greg on when misdiagnosis is likely to occur.

Gina Mullane (12:03):
You mentioned SCA and Huntington's can have similar symptoms and are caused by the same DNA patterns. Is misdiagnosis common?

Greg Klassen (12:12):
It does happen. There are a whole bunch of people that do not know, there's Scott type or SCA3 type, or even that it's SCA3. There's something called Friedreich ataxia that they don't... it's not genetic that they found. I mean, there is no treatment so misdiagnosis doesn't carry with the burden of not getting your treatments. But I'm sure there are other people that, I mean, they just look at you and think that you're drunk or somehow out of it. If you don't know you have the disease and the mood swings you don't know where that's coming from. So diagnosis helps.

Gina Mullane (13:21):
So in what ways is the rare disease community helping to build awareness and help people become more informed about this condition?

Greg Klassen (13:30):
So you might be aware that the NFL just added the word ataxia to their concussion protocol because of the Miami quarterback who got up and stumbled around. That is not hereditary ataxia. But nevertheless, the world was introduced to the term ataxia, which I thought was good. The Cure Rare Disease is constantly doing videos and other kinds of social media to make people aware. There's a foundation called the National Ataxia Foundation that does a good job in letting other people know what ataxia is. And there are some celebrities I understand, that have come down with this rare disease that are using their status to let people know that this is a disease that needs treatment.

Gina Mullane (14:57):
And as I think we all know, it's costly and lengthy to develop treatments, and sometimes that can create a barrier to access for people to get access. How can we make therapies like this as they become developed and become available more accessible to patients who need them?

Greg Klassen (15:21):
Let's not let treatment for the masses stop us from finding a treatment. Let's find the treatment and then worry about making it accessible.

Gina Mullane (15:38):
Great point.

Greg Klassen (15:38):
That's my thoughts.

Gina Mullane (15:41):
So I know you and your family are working with Cure Rare Disease to raise funds and develop a treatment. How is this collaboration working and how do you think it will help to expedite development of a treatment?

Greg Klassen (15:56):
Yeah, so as you and your community know, the medical science community is a vast community. There's no way that I alone could navigate the scientists, the doctors, and other researchers that administer the thing. The FDA. All the testing that goes into that. CRD is critical in bringing all those components together and the collaboration needed to make a cure possible.

Gina Mullane (16:39):
It sounds like a really powerful partnership, collaboration going on.

Greg Klassen (16:44):
Yes.

Gina Mullane (16:45):
You mentioned antisense oligonucleotides or ASO as a potential therapy or treatment in 2024 that you're looking toward, and can you tell us a little bit about that specific approach and what's involved in that?

Greg Klassen (17:03):
Yeah, so ASO, as your community will undoubtedly know targets the RNA, which in time... It's not like targeting the DNA, which once you target is good for lifetime. The RNA regenerates itself over time. So the ASO targets the RNA, but it is still considered a gene therapy because it cures the disease. The ASO targets the RNA, which generates the protein that in my case, is toxic to the cerebellum. So by changing my DNA, the theory is that I won't generate this toxic protein. So that's on the technical side.

Todd Poley (18:16):
Cure Rare Disease is in the midst of preclinical testing for its SCA3, ASO therapy. Because ASOs are a novel technology, they require some unique considerations in the preclinical phase. For example, one point that could be unique to an ASO is that time in blood can be relatively brief hours to a few days, whereas the effects in cells can be long-lasting days to weeks or even months. This is one reason tissue analysis is often included in ASO programs. Example, tissues include liver, kidney, spleen, lungs, and heart. As these tissues are known to accumulate ASOs or are often noted in toxicology studies, this data can provide further information on the potential effects in patients. Let's hear from Greg on what participation in this clinical trial could mean for him, his family, and the future of SCA3.

Gina Mullane (19:15):
It must be very exciting to see the progress being made in developing this ASO treatment. What would finding a cure to SCA3 mean for you personally?

Greg Klassen (19:26):
For me, a cure is well to stop SCA3 in its tracks, but leave me with my speech the way it is, my swallowing, which I choke on and my mood fluctuations. But for my children and all those that are not yet symptomatic, I mean, this could be the cure that... Excuse me. I mean, they may never have to experience the symptoms that I have. And that would just be so wonderful, if my life somehow could be used in a way to stop this disease from the family, ravaging mood swings, the gait issues. That would be what a cure looks like. I mean, that to me is the future. It's not me. It's for my children and all those that are asymptomatic. I'm sorry.

Gina Mullane (20:48):
Don't be sorry. It certainly brings meaning to the work that we do every day in our jobs as being part of the research community and stories like yours and the passion that you are putting toward this and the emotion that you're feeling now. It really does motivate us every day to work harder and do better. So thank you so much for sharing and being so honest. To me, you're putting forth an incredible legacy for not only your family but the whole community and you're brave to share this and to motivate us all. So thank you for that. What more would you like to share? Is there anything else from your perspective that you think is important for us to know in the research community about the disease, your experience? Anything else about the development process of bringing a cure forward?

Greg Klassen (22:04):
There are real people on the other end of this disease. You guys have the knowledge and the brain power that I don't have that can make these solutions, these cures possible. You're affecting real people. Go forth and make sure that your diligence cures people.

Gina Mullane (22:48):
Thank you so much, Greg, for being here today on Vital Science. It was a pleasure speaking with you.

Greg Klassen (22:53):
Gina, thank you for the interview. You did a fine job asking questions. Thank you so much.

Todd Poley (23:04):
Greg Klassen is a board member at Cure Rare Disease. Looking ahead to our July episode of Vital Science, we'll speak with one of our in-house regulatory experts on the recently passed FDA Modernization Act and its implications on preclinical testing. Did you know that Charles River has a sister podcast, Eureka's Sounds of Science? This monthly podcast shares scientific, patient and advocacy perspectives on trending issues in the drug development industry. You can subscribe to Vital Science and Sounds of Science on Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Until then, thanks for listening.