Really interested in the polypeptide vaccine. I did a little bit of my first postdoc on peptide vaccines for eliciting T cell responses, but this is really cool to go after innate responses using a cyclic structure.
If I can keep you interested, I will count that as a win! It's exciting to see the immune system becoming the forefront of medicine.
What are your general thoughts on these peptide treatments, are you bullish? I'm still worried that in a treatment scenario, peptides would have a poor PK.
To be honest, I drifted away from it a bit. We were working on peptides with altered amino acids to enhance bioavailability and stability (essentially making them more protease resistant). They were stable in vitro, but failed to generate much of an immune response in vivo, unfortunately.
My 12 year-old cat gets monoclonal antibody injections for her arthritis, which affects her lower back and elbows. The brand name is Solensia (frunevetmab), which is made specifically for cats. I inject it SQ once a month; she just had her fifth of sixth initial doses. She's been on twice-daily gabapentin for about two years and still gets that, but the Solensia seemed like it was having an effect by around the third month. She could never jump onto my office chair before, but now she does it regularly by shooting through the space between the armrest and the seat, and the office has a hard floor, which makes it even more impressive (to me). She's also able to jump onto my bed now, and previously required a ramp. She's not just barely making it onto those surfaces, either. Her movement is nearly normal. Her other new trick is to blast down the entire length of the house at at dead run. It's not the usual graceful cat motion, but it's pretty impressive for an arthritic old lady.
If you ask Wikipedia, frunevetmab "is a cat-specific monoclonal antibody (a type of protein) designed to recognize and attach to a protein called nerve growth factor that is involved in the regulation of pain. When frunevetmab binds to nerve growth factor, it prevents the pain signal from reaching the brain." That all leaves me none the wiser, but it's been moderately effective at making my cat more comfortable.
I'm happy to hear about the success your cat has had with the antiNGF treatment. mAbs (monoclonal antibodies) are a huge drug class for their ability to inhibitor other proteins (as you pointed out). I had heard about some antibodies being developed for arthritis, but hadn't fully read it into these. I also didn't realize that these had made their way into the vet space. I'm going to guess as some of these big name-brand drugs come off patent, we will continue to see more generics and biosimilars reaching pets.
I actually spent a chunk of time studying NGF. It's an interesting molecule. I hadn't realized that there were pain drugs directed towards its inhibition, but it makes sense! Above all else, it's fantastic that it's helping increase your cats quality of life. When I studied NGF, we were interested in it's upregulation of neuron pain receptors and sensitization of existing pain receptors, like TRPV1.
Fun fact, TRPV1 is the same receptor that responds to capsaicin, the key ingredient in hot sauce.
I know of one other notable human drug that's available for cats, although it's obtainable only via the black market, and that's Remdesivir. https://pubmed.ncbi.nlm.nih.gov/37439383/ I found out about it the hard way, when a vet at an emergency clinic recommended it. He couldn't prescribe it, though, and by the time I got approved by someone who could get it, it was too late for the cat in question. It's contraindicated for people, but Remdesivir is very effective at treating feline infectious peritonitis, which is almost always fatal otherwise.
In general it's pretty amazing what's available for pets these days, although it can't be amazing enough. In 2007 I had a young cat who got a kidney transplant at the University of Wisconsin/Madison vet clinic. At the time it wasn't possible to transplant kidneys in dogs; not sure whether that's a thing yet or whether the same barriers to treatment still exist. In cats the donor gives up just one kidney so it doesn't require his ultimate sacrifice, and if there's any function in the native kidneys they're left in. My cat ended up with three kidneys. Anyway, the point is that crazy people like me will spend anything they can on pets, so it makes financial sense for researchers to keep making surgical and pharmacological advancements.
I had never heard of FIP or knew that Remdesivir was used to treat it. Sometimes I get the feeling you should have the biotech blog haha. It's an interesting article. It looks like Remdesivir is actually a prodrug and metabolized to an adenosine analog. I wonder if you could just purchase adenosine in some form for treatment. Although, that therapeutic window is pretty tight.
It's amazing there is so much gatekeeping by these large biotech companies - particularly since they don't seem terrible interested in the vet tech space. I get the impression that they just don't see it as profitable enough compared to their billion dollar human markets.
I'm actually working with a few colleagues (mostly nights and weekends) on a startup company to translate some human drugs to the vet space. Not quite ready to give more details yet, but I'll give a full debrief at some point.
You probably already know that Americans spend over $100 billion a year on their pets. It seems like the drug companies would be more sensible of that. Volume would go up and prices would go down if Remdesivir (to name just one drug) were readily available to veterinarians. Its off-label use for FIP isn't commonly known even by vets; once I found out about it, I made sure my local vet had all the information he needed to pass on to other owners of cats with the diagnosis.
I really wish you the best on that startup. There's a huge unmet demand for better, safer pet medications and I'd think the upside to what you're trying to do would be virtually unlimited. Please do provide an update on that project when you can.
Will there be other uses for these muscle preservation drugs instead of just weight loss? What about aging in general? Will it help to build muscle mass if weight loss isn’t the goal?
There’s a great chance they will or already are being used off label by competitive athletes for improving strength and overall changing body composition.
Organ transplants have to be up there with one of the coolest things our medical industry can do.
It will just get even cooler when we have the ability to grow them in the lab or derive them from organoids!
Great roundup again, David.
Really interested in the polypeptide vaccine. I did a little bit of my first postdoc on peptide vaccines for eliciting T cell responses, but this is really cool to go after innate responses using a cyclic structure.
If I can keep you interested, I will count that as a win! It's exciting to see the immune system becoming the forefront of medicine.
What are your general thoughts on these peptide treatments, are you bullish? I'm still worried that in a treatment scenario, peptides would have a poor PK.
To be honest, I drifted away from it a bit. We were working on peptides with altered amino acids to enhance bioavailability and stability (essentially making them more protease resistant). They were stable in vitro, but failed to generate much of an immune response in vivo, unfortunately.
My 12 year-old cat gets monoclonal antibody injections for her arthritis, which affects her lower back and elbows. The brand name is Solensia (frunevetmab), which is made specifically for cats. I inject it SQ once a month; she just had her fifth of sixth initial doses. She's been on twice-daily gabapentin for about two years and still gets that, but the Solensia seemed like it was having an effect by around the third month. She could never jump onto my office chair before, but now she does it regularly by shooting through the space between the armrest and the seat, and the office has a hard floor, which makes it even more impressive (to me). She's also able to jump onto my bed now, and previously required a ramp. She's not just barely making it onto those surfaces, either. Her movement is nearly normal. Her other new trick is to blast down the entire length of the house at at dead run. It's not the usual graceful cat motion, but it's pretty impressive for an arthritic old lady.
If you ask Wikipedia, frunevetmab "is a cat-specific monoclonal antibody (a type of protein) designed to recognize and attach to a protein called nerve growth factor that is involved in the regulation of pain. When frunevetmab binds to nerve growth factor, it prevents the pain signal from reaching the brain." That all leaves me none the wiser, but it's been moderately effective at making my cat more comfortable.
I'm happy to hear about the success your cat has had with the antiNGF treatment. mAbs (monoclonal antibodies) are a huge drug class for their ability to inhibitor other proteins (as you pointed out). I had heard about some antibodies being developed for arthritis, but hadn't fully read it into these. I also didn't realize that these had made their way into the vet space. I'm going to guess as some of these big name-brand drugs come off patent, we will continue to see more generics and biosimilars reaching pets.
I actually spent a chunk of time studying NGF. It's an interesting molecule. I hadn't realized that there were pain drugs directed towards its inhibition, but it makes sense! Above all else, it's fantastic that it's helping increase your cats quality of life. When I studied NGF, we were interested in it's upregulation of neuron pain receptors and sensitization of existing pain receptors, like TRPV1.
Fun fact, TRPV1 is the same receptor that responds to capsaicin, the key ingredient in hot sauce.
I know of one other notable human drug that's available for cats, although it's obtainable only via the black market, and that's Remdesivir. https://pubmed.ncbi.nlm.nih.gov/37439383/ I found out about it the hard way, when a vet at an emergency clinic recommended it. He couldn't prescribe it, though, and by the time I got approved by someone who could get it, it was too late for the cat in question. It's contraindicated for people, but Remdesivir is very effective at treating feline infectious peritonitis, which is almost always fatal otherwise.
In general it's pretty amazing what's available for pets these days, although it can't be amazing enough. In 2007 I had a young cat who got a kidney transplant at the University of Wisconsin/Madison vet clinic. At the time it wasn't possible to transplant kidneys in dogs; not sure whether that's a thing yet or whether the same barriers to treatment still exist. In cats the donor gives up just one kidney so it doesn't require his ultimate sacrifice, and if there's any function in the native kidneys they're left in. My cat ended up with three kidneys. Anyway, the point is that crazy people like me will spend anything they can on pets, so it makes financial sense for researchers to keep making surgical and pharmacological advancements.
I had never heard of FIP or knew that Remdesivir was used to treat it. Sometimes I get the feeling you should have the biotech blog haha. It's an interesting article. It looks like Remdesivir is actually a prodrug and metabolized to an adenosine analog. I wonder if you could just purchase adenosine in some form for treatment. Although, that therapeutic window is pretty tight.
It's amazing there is so much gatekeeping by these large biotech companies - particularly since they don't seem terrible interested in the vet tech space. I get the impression that they just don't see it as profitable enough compared to their billion dollar human markets.
I'm actually working with a few colleagues (mostly nights and weekends) on a startup company to translate some human drugs to the vet space. Not quite ready to give more details yet, but I'll give a full debrief at some point.
Amazed at the kidney transplant!
You probably already know that Americans spend over $100 billion a year on their pets. It seems like the drug companies would be more sensible of that. Volume would go up and prices would go down if Remdesivir (to name just one drug) were readily available to veterinarians. Its off-label use for FIP isn't commonly known even by vets; once I found out about it, I made sure my local vet had all the information he needed to pass on to other owners of cats with the diagnosis.
I really wish you the best on that startup. There's a huge unmet demand for better, safer pet medications and I'd think the upside to what you're trying to do would be virtually unlimited. Please do provide an update on that project when you can.
Will there be other uses for these muscle preservation drugs instead of just weight loss? What about aging in general? Will it help to build muscle mass if weight loss isn’t the goal?
There’s a great chance they will or already are being used off label by competitive athletes for improving strength and overall changing body composition.