Using Data Collaboration During Development of New Cardiovascular Therapies
If researchers are interested in producing the next generation of super effective cardiovascular therapies, they’re going to need to team up. A new review published in Clinical Science argues that tandem pore potassium ion channels found in cardiovascular tissues could be targeted in new ways if researchers are willing to reach beyond the status quo of single drug therapy.
This review joins a growing body of prior research, finding that while drugs targeting the channels have many potential applications, the theoretically possible modular and granular control of the channels’ flow through makes them ideal for cardiovascular drug development.1 2 Granular control, however, is only possible with a comprehensive understanding of the channel system and a molecular toolbox to exercise that control. To get the most out of targeting the channels, researchers will need to work hand in hand with other research groups who are investigating the channels for other purposes. By sharing data, researchers will be able to accelerate their efforts while also helping their colleagues. Full data sharing collaboration simply won’t be possible without a comprehensive software platform to facilitate the relationship, though.
Utilizing K2P Channels and Their Benefits
Known also as K2P channels or potassium leak pathways, K2P channels regulate the concentration gradient of the ion that they’re named after by either permitting it or forbidding it from entering or leaving the cell. Specifically, K2P channels help to increase the speed of repolarization after an action potential, which means that interfering with their natural function is risky, but potentially very rewarding.3 If K2P channels are reversibly partially blocked, the high level effect within the cardiovascular system is lower cardiac muscle contractility and thus a lower heart rate. If K2P channels are permanently blocked, there will be a lethally noxious result along the lines of another ion channel blocker, tetrodotoxin.4
Hitting the exact therapeutic window of K2P channels has too many benefits to pass up. Tandem potassium ion channels have been implicated in heart failure, and researchers have readily identified the channels as a juicy drug target.5 6 The most obvious application of drugs targeting K2P channels is inhibiting their flow through in order to inhibit the erratic resting potential in diseases like arrhythmia.7
That’s not all that K2P channels can offer, though. Aside from arrhythmia and heart failure, the review notes that K2P channel targeted drugs could easily be used to increase or decrease heart rate in metered ways. Thanks to advances in drug design, it’s not far fetched to envision a biologic which could lock a proportion of the heart’s K2P channels to a certain flow through, ensuring that neither tachycardia or bradycardia could persist for long.8
Collaborating to Personalize Cardiovascular Medicine
Some researchers have gone as far as to say that K2P channels could be used in personalized medicine, as the channels are sensitive enough to be blocked in differing proportions by different chemicals.9 To realize this goal, researchers need to develop the following:
- Reversible K2P inhibitors of several strengths, which would reduce heart rate
- Reversible K2P inducers of several strengths, which would increase heart rate
- K2P “door jambs” of several strengths which would prevent extremes of heart rates
- K2P antagonists which would temporarily fully block the channel or force it all the way open for use in emergency situations
- Genetic tests to quickly determine a given patient’s K2P isomorph
- Strategies for using multiple types of K2P inhibitors and inducers in conjunction clinically
It’s clear that a given research lab would handle only one of these bullet points. It’s also clear that research data from any one of the bullet points would be intensely useful for a group handling a different bullet point to get their hands on. Because of this, the cardiovascular therapies of the future will be built on a mountain of shared data and collaborative investigation– anything less would spoil the entire concept of modular therapy.
2P channels are useful outside of cardiovascular medicine too, but that brings a bucket of risks that researchers will have to work around. Because K2P channels are found in many different cell types in critical roles, the specificity and localization of any K2P targeted therapies need to be spot on. A heart-targeted K2P channel drug would have deleterious effects if it were to act on the K2P channels in the patient’s brain, and vice versa. Specifically, K2P channel targeted drugs can’t:
- Cross the blood brain barrier if their target is elsewhere
- Enter the cardiovascular system if their target is elsewhere
- Degrade into subunits which might fully block K2P channels after binding to the channel initially
- Deform the K2P channels irreversibly as a result of binding to the channel initially
- Damage off-target cells by altering ambient potassium concentration beyond their ability to cope
- Reduce the production of ATP and other sources of cellular energy used to power ion channels
Researchers will find a way to avoid these pitfalls. It’s undeniable that future therapy regimens using multiple options will have better outcomes for the patient, as the review harps on. This means that researchers will need to create large working groups so that each can build their portion of the new therapy with the expectation that other groups will build off of their final product as well as their intermediary data. This kind of deep collaboration doesn’t happen smoothly with weak laboratory software, so research groups will need to adopt a platform that can keep up with the needs of their research.
Collaborative Science Solutions is the collaboration, data sharing, workflow management, modeling and simulation, experiment planning and cardiovascular research software that the cardiovascular disease researchers of today will use to produce the K2P channel targeted therapies of tomorrow. Using Science Solutions, your team will be able to seamlessly share insights with your collaborators in order to build knowledge which will be used in K2P channel drug development. Contact us today to find out how you can use Science Solutions to start combining your lab’s efforts with other groups in a quick and powerful way to provide calibratable cures to cardiovascular diseases.
- “Research Into The Therapeutic Roles Of Two-Pore-Domain Potassium Channels.” October 2010, https://www.researchgate.net/publication/47448753_Research_into_the_therapeutic_roles_of_two-pore-domain_potassium_channels ↩
- “Emerging Roles For Two-Pore-Domain Potassium Channels And Their Therapeutic Impact.” October 2008, https://www.researchgate.net/publication/23287866_Emerging_roles_for_two-pore-domain_potassium_channels_and_their_therapeutic_impact ↩
- “International Union Of Pharmacology. LV Nomenclature And Molecular Relationships Of Two-P Potassium Channels.” December 2005, http://pharmrev.aspetjournals.org/content/57/4/527.long ↩
- “Tetrodotoxin: Chemistry, Toxicity, Source, Distribution, And Detection. February 2014, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942760/ ↩
- “Stretch-activated Two-Pore-Domain (K2P) Potassium Channels In The Heart: Focus On Atrial Fibrillation And Heart Failure.” January 2017, http://www.sciencedirect.com/science/article/pii/S0079610717300287 ↩
- “Atrial Fibrillation: Therapeutic Potential Of Atrial K+ Channel Blockers.” October 2016, http://www.sciencedirect.com/science/article/pii/S0163725816301814 ↩
- “Inhibition Of Cardiac Two-Pore-Domain K+ (K2P) Channels– An Emerging Antiarrhythmic Concept.” September 2014, http://www.sciencedirect.com/science/article/pii/S0014299914004361 ↩
- “Perspectives On The Two-Pore-Domain Potassium Channel TREK-1 (TWIK-Related K+ Channel 1). A Novel Therapeutic Target?” November 2015, http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b00671 ↩
- “What Have We Learned From Two-Pore Potassium Channels? Their Molecular Configuration And Function In The Human Heart.” 2012, http://www2.sci.u-szeged.hu/ABS/2012/Acta%20HPb/5693.pdf ↩