Natalie Nairn, PhD, Vice President of CDP Therapeutics at Blaze Bioscience talks about using scorpion venom to possibly target and treat arthritis.
How did the idea of using scorpion venom to treat arthritis come about?
NAIRN: Blaze Bioscience was co-founded by Heather Franklin and Jim Olson, who is a pediatric neuro-oncologist at Fred Hutchinson Cancer Research Center. Blaze was founded around Tumor Paint ®, which uses a CDP miniprotein from scorpions for real-time image-guided tumor resection surgery. These CDP miniproteins are classically associated with snake and scorpion venoms, but are found throughout all the kingdoms of life, such as in potatoes, violets, and grasshoppers. Blaze formed an ongoing collaboration with Dr. Olson’s lab to investigate other uses for CDP miniproteins. These miniproteins have evolved with a lot of drug-like properties in nature. So, we wanted to explore how they might be used for other therapeutic applications and look at what interesting biodistribution properties they may have to different tissues in the body. We were screening some of these CDP miniproteins looking for where they might go and discovered this set that spontaneously accumulates in the cartilage throughout the body. So, all your articular cartilage joints like your hips, knees, fingers as well as your fibrocartilage joints, such as the intervertebral discs of your spine. This is one of those discoveries in science that you can never anticipate and is exciting. It was obvious to us that this can be an excellent way to deliver drugs to inflamed joints of arthritis and get them concentrated where they need to be and help the drugs avoid other issues where they could otherwise cause damage.
How did you study this?
NAIRN: We studied this by radiolabelling various CDP miniproteins and then looked at different tissues to see where they went in the body. We were screening dozens of them and looking for ones that can penetrate the brain for delivery to the central nervous system. We were also looking at other tissues, hypothesizing there would be CDPs with unique tissue biodistributions. You can see these cartilage-specific CDP miniproteins lighting up very obviously in the spine and the joints of the animals that we were testing.
How can something that is poisonous actually help people?
NAIRN: First of all, scorpion and snake venoms are evolved for the particular prey that they’re trying to attack and venoms are made up of multiple components. Some components may have poisonous effects in certain species, but other components may not. We have conducted early tolerability studies with these molecules, and they look well tolerated. Similarly, our Tumor Paint ® tozuleristide is made with a different scorpion venom component and appears well tolerated in humans. We can combine the cartilage-targeting components from the scorpion venom with a steroid such as triamcinolone acetonide and actually safely deliver these to the joints while avoiding a lot of the toxic side effects of the steroid. This can result in a safer drug!
How does this compare to current treatments available for arthritis?
NAIRN: Currently in a lot of arthritis diseases, patients are given steroids. However, they must be given sparingly because of the strong toxic side effects they can have such as immunosuppression. Steroids can also cause hypertension, glaucoma, and bone necrosis. So, they’re only used when patients have disease flares or in the lowest dose that their doctors are able to prescribe where they try to balance the side effects with the pain relief. By doing this study, we hope that doctors will be able to give these to patients for a longer time and get greater relief from pain and have greater mobility without having to balance as much side effects in the patients.
You did a study with this on rats? Can you tell me about the findings of that study?
NAIRN: Yes. We used a rat model of rheumatoid arthritis where the rats have inflamed painful joints just like patients. We dosed our molecule, which is a CDP steroid conjugate, and compared it to dosing just the steroid alone in the rats. It’s well known that steroid alone can reduce inflammation but can also cause toxicity. When we linked the steroid to our CDP miniprotein, it also relieved the arthritis in the rats. We could measure that their joint swelling went back down to a normal sized joint. We could also look at the rats’ organs such as the spleen and the thymus to see if they shrank, which is indicative of the immune suppression that you get with steroids. When we give the steroid alone, you can see these organs getting smaller in these rats whereas when we dosed our CDP steroid conjugate, the organs stayed a normal size.
What are the next steps with this?
NAIRN: Our target product profile for developing this drug candidate is a therapeutic that patients can administer to themselves at home, subcutaneously under the skin, and only once a week or less. We are doing modeling and translational work to show that we anticipate having the right formulation and that we’ll be able to achieve that product profile in patients. Then, we can move into our IND enabling studies and bring this into the clinic. We’re also speaking with pharma companies about potential partnerships for moving this forward.
Do you expect this type of treatment to potentially last longer than current treatments available?
NAIRN: Currently, there are several different ways that steroids are dosed. Most frequently they’re just dosed orally. So, they’re a pill that’s taken once a day, but again, only for a limited period of time. Patients that have osteoarthritis sometimes have an injection in the joint. But it must be injected directly into the joint you want to treat. If you have more than one joint, there’s only so many joints you can inject. You’re only allowed to do those injections quite infrequently due to various issues with that. So, we envision that this will be a convenient dosing solution for these patients that’s also more comfortable and treats all their joints at the same time.
What do you think this will mean for someone who’s suffering with arthritis?
NAIRN: We hope that they’ll be able to be treated with steroids on a chronic basis whereas otherwise they can’t be because of the toxic side effects. We hope that they would have a reduced pain and increased mobility on an ongoing basis.
How far away do you think you are from a human clinical trial?
NAIRN: We anticipate that we could bring this into the clinic within 18 months.
Is there anything else you feel people should know?
NAIRN: I’ll mention that we have other programs using CDP miniproteins for additional diseases we’re working on including immuno-oncology, other oncology indications, and treatments of inflammation including GI and CNS disorders. These CDP miniproteins have low immunogenicity and drug-like properties. They’re very potent and very stable. We believe there are a lot of great applications for these molecules.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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NATALIE NAIRN
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