(Total Views: 591)
Posted On: 02/03/2025 6:54:44 AM
Post# of 149929
ohm20
This morning I spoke with my friend ChatGpt about your post earlier,
The transglutaminase-2 enzyme, here is the reply.
The transglutaminase-2 enzyme that it targets needs high levels of intracellular CA-2+ to activate. Leronlimab downregulates that CA-2+.
It sounds like you're discussing Leronlimab's mechanism in relation to transglutaminase-2 (TG2) and calcium (Ca²⁺) regulation. Leronlimab, a CCR5 antagonist, is primarily known for its immunomodulatory effects, particularly in reducing inflammation and blocking HIV entry into cells. If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation, since TG2 requires high Ca²⁺ concentrations to become active.
Are you looking for more details on how Leronlimab affects calcium signaling, TG2's role in disease, or something else?
If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation since TG2 requires high Ca²⁺ concentrations to become active. Could this be a cure for HIV
Leronlimab’s ability to downregulate intracellular Ca²⁺ could indeed have interesting implications for transglutaminase-2 (TG2) activity, but calling it a cure for HIV would be a big leap. Here’s why:
HIV Persistence & Reservoirs – A true cure for HIV would require eliminating or functionally silencing latent viral reservoirs. Leronlimab primarily blocks the CCR5 co-receptor, preventing new infections but not necessarily eradicating existing reservoirs.
TG2’s Role in HIV – TG2 has been implicated in inflammatory processes and fibrosis, particularly in HIV-related immune dysfunction. If Leronlimab reduces TG2 activation by lowering intracellular Ca²⁺, it might help mitigate HIV-associated inflammation and tissue damage, but this doesn’t mean it eradicates the virus itself.
Functional Cure vs. Sterilizing Cure – A functional cure means HIV is controlled without ART, while a sterilizing cure means the virus is completely eliminated. Leronlimab has shown promise in reducing viral load and inflammation, but there’s no evidence yet that it can fully clear the virus from the body.
Combination Strategies – Many believe a cure for HIV will require a combination approach: latency-reversing agents, immune-based therapies, and possibly gene-editing technologies like CRISPR. Leronlimab could be part of a broader strategy, but by itself, it’s unlikely to be a standalone cure.
If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation since TG2 requires high Ca²⁺ concentrations to become active. Could Leronlimab work as a contraceptive for HIV?
That’s an interesting angle! If Leronlimab downregulates intracellular Ca²⁺, and since transglutaminase-2 (TG2) activation depends on high Ca²⁺ levels, there could be an indirect impact on HIV’s ability to establish infection or persist. However, whether this mechanism would make Leronlimab an effective contraceptive for HIV transmission is another question.
Here’s what we know:
1. Leronlimab as an HIV Blocker
Leronlimab is a CCR5 antagonist, meaning it blocks the CCR5 co-receptor that many HIV strains (R5-tropic) use to enter immune cells.
This prevents new infections but doesn’t clear existing ones.
2. The Role of Calcium in HIV and TG2
HIV manipulates calcium signaling during infection, and Ca²⁺ levels play a role in viral replication and immune activation.
TG2 is involved in inflammation, immune responses, and potentially fibrosis in chronic HIV. If TG2 is less active due to reduced Ca²⁺, it might affect the local cellular environment in ways that impact HIV persistence or transmission.
3. Could This Prevent HIV Transmission?
A contraceptive for HIV (or a preventative method) would need to stop viral transmission at mucosal surfaces (vaginal, rectal, etc.).
Leronlimab primarily works inside immune cells, meaning it’s not directly a topical or systemic barrier against HIV entry like PrEP (e.g., Truvada, Descovy).
However, if its effects on intracellular Ca²⁺ significantly reduce HIV’s ability to infect new cells or establish reservoirs, there could be potential for preventing infection after exposure—similar to post-exposure prophylaxis (PEP).
4. Could Leronlimab Be Used for HIV Prevention?
As PrEP? Possibly, but current PrEP drugs work by preventing viral replication once HIV enters the body, not by targeting calcium signaling.
As a microbicide or topical gel? Unlikely, since its mechanism involves systemic immune cell interactions rather than direct mucosal protection.
Conclusion
Leronlimab’s ability to block CCR5 is already a strong preventive measure against HIV infection for R5-tropic strains. If its Ca²⁺-lowering effect further disrupts TG2 or other HIV-related pathways, it could enhance its antiviral properties. However, it wouldn’t function like a traditional contraceptive (such as a barrier or microbicide).
Would you like to explore whether Leronlimab could be used in combination with other HIV prevention methods?
Yes
Leronlimab could definitely be considered as part of a combination strategy for HIV prevention, but let’s break it down into different approaches to see how it might fit in:
Leronlimab could definitely be considered as part of a combination strategy for HIV prevention, but let’s break it down into different approaches to see how it might fit in:
1. Leronlimab + Existing PrEP (Pre-Exposure Prophylaxis)
Current PrEP drugs (Truvada, Descovy): These use tenofovir/emtricitabine to prevent HIV from replicating after entry.
How Leronlimab could help: Since it blocks the CCR5 receptor, it could complement PrEP by providing an additional layer of defense, especially against R5-tropic HIV strains.
Potential Benefit: This combo could reduce the chances of infection even further, especially for individuals at high risk.
2. Leronlimab as a Long-Acting Injectable for HIV Prevention
Current injectables like Cabotegravir (Apretude) offer long-lasting protection against HIV.
Leronlimab is already an antibody therapy, meaning it could be formulated as a long-acting injection.
Potential Benefit: If it’s shown to reduce intracellular Ca²⁺ and interfere with HIV’s replication machinery, it might provide sustained protection similar to or better than Cabotegravir.
3. Leronlimab + Microbicides or Topical Gels
Microbicides are gels or creams that can be applied to vaginal/rectal tissues to block HIV transmission.
If Leronlimab affects intracellular Ca²⁺, it might reduce the ability of HIV to infect local immune cells in mucosal tissues.
Potential Benefit: If it could be formulated into a gel or suppository, it could work as a mucosal immune modulator, reducing local inflammation and HIV susceptibility.
4. Leronlimab + PEP (Post-Exposure Prophylaxis)
PEP (like Truvada + Isentress) is taken after exposure to prevent HIV infection.
If Leronlimab lowers intracellular Ca²⁺, it might make cells less hospitable to viral replication, improving PEP’s effectiveness.
Potential Benefit: Faster immune response and reduced viral establishment in early infection.
Final Thoughts: Could Leronlimab Be a Standalone HIV Preventative?
For R5-tropic HIV: It’s already a strong candidate since it blocks CCR5.
For all HIV strains: It might need to be combined with other strategies.
Its impact on Ca²⁺ and TG2: If it significantly interferes with HIV replication or immune activation, it could enhance existing prevention methods.
Would you be interested in seeing how Leronlimab compares to other experimental HIV prevention strategies (e.g., vaccines, gene editing, etc.)?
Would you be interested in seeing how Leronlimab compares to other experimental HIV prevention strategies (e.g., vaccines, gene editing, etc.)?
Yes
There are several experimental HIV prevention strategies in development, and Leronlimab could potentially fit into this evolving landscape. Let’s compare it to other cutting-edge approaches:
1. Broadly Neutralizing Antibodies (bNAbs)
How They Work: These antibodies target multiple strains of HIV by blocking key viral proteins (e.g., CD4-binding sites on gp120).
Examples: VRC01, 3BNC117, 10-1074.
How Leronlimab Compares:
Leronlimab is an anti-CCR5 monoclonal antibody, meaning it prevents HIV from attaching to cells rather than directly neutralizing the virus.
If it has additional effects on intracellular Ca²⁺ and TG2, it could offer immune modulation beyond viral blocking.
2. Long-Acting Injectable PrEP (Cabotegravir, Lenacapavir)
How They Work: These drugs inhibit HIV replication (integrase inhibitors like Cabotegravir, capsid inhibitors like Lenacapavir).
How Leronlimab Compares:
Leronlimab works earlier in the infection process, blocking entry instead of replication.
If it can also lower intracellular Ca²⁺, it might disrupt HIV’s ability to establish infection, making it a potential addition to long-acting PrEP.
3. Gene Editing (CRISPR-based HIV Cure Strategies)
How They Work: CRISPR is being tested to cut out HIV genes from infected cells or modify genes to make humans resistant (e.g., CCR5 gene knockout).
Examples: Trials using CRISPR to edit the CCR5 gene, similar to the mutation found in the famous “Berlin Patient” and “London Patient” (who were cured after bone marrow transplants with CCR5 mutations).
How Leronlimab Compares:
Instead of permanently modifying CCR5, Leronlimab temporarily blocks it, making it a safer and more reversible approach.
Potential Combo? Leronlimab could be used alongside CRISPR to temporarily block CCR5 while gene-editing therapies take effect.
4. HIV Vaccines (mRNA & Other Approaches)
How They Work: Teach the immune system to recognize and attack HIV before infection.
Examples:
Moderna’s mRNA HIV vaccine (similar to COVID vaccines).
Mosaic vaccine trials (using adenovirus vectors).
How Leronlimab Compares:
Vaccines aim to train the immune system, while Leronlimab directly blocks infection.
If Leronlimab has long-term immune-modulating effects (via Ca²⁺ and TG2 pathways), it could complement vaccines by reducing inflammation and viral susceptibility.
5. Stem Cell & CAR-T Cell Therapy
How They Work:
Stem cell transplants with CCR5-deficient donor cells (e.g., “Berlin Patient”).
CAR-T cells engineered to kill HIV-infected cells.
How Leronlimab Compares:
Leronlimab is far less invasive than a transplant or gene therapy.
If it helps regulate intracellular Ca²⁺ and immune responses, it could reduce HIV-associated immune dysfunction, making it useful in combination with immune-based therapies.
Where Leronlimab Fits In
Short-Term Prevention: Leronlimab could be part of a long-acting PrEP strategy (similar to Cabotegravir).
Long-Term Strategies: It could work alongside CRISPR or stem cell therapies to help manage immune response and block infection while more permanent solutions take effect.
Combination Use: If its intracellular Ca²⁺ effects impact viral replication, it might enhance other HIV treatments or reduce chronic inflammation in long-term HIV patients.
Final Thought: Could Leronlimab Become a Game-Changer?
Leronlimab is already in clinical trials for HIV treatment and could have a role in prevention if further studies confirm its ability to disrupt Ca²⁺-mediated pathways important for HIV replication.
Would you like to explore any specific area further (e.g., clinical trial data, formulation as a PrEP option, etc.)?
Great! Let’s break it down further. Since you’re interested in Leronlimab’s potential as an HIV prevention option, we can look at:
Current Clinical Trial Data on Leronlimab for HIV
How Leronlimab Could Be Used for PrEP
Potential Challenges & Next Steps
1. Current Clinical Trial Data on Leronlimab for HIV
Leronlimab has been in clinical trials for HIV treatment rather than prevention so far. Some key takeaways:
Completed Trials (HIV Treatment)
Leronlimab + HAART (Highly Active Antiretroviral Therapy)
Showed reduced viral load in patients with multi-drug-resistant HIV.
Maintained viral suppression without severe side effects.
Monotherapy Trials (Leronlimab Alone)
Some trials tested Leronlimab as a standalone treatment for HIV.
It reduced viral load but wasn’t enough alone to maintain long-term suppression.
What This Means for HIV Prevention
Since Leronlimab effectively blocks CCR5-tropic HIV, it could work similarly to Maraviroc (another CCR5 blocker used for prevention & treatment).
However, there’s no official PrEP trial yet, meaning it hasn’t been tested specifically in people before exposure to see if it prevents infection.
2. How Leronlimab Could Be Used for PrEP (HIV Prevention)
If Leronlimab were tested for PrEP, here’s how it could fit in:
Option 1: Long-Acting Injectable PrEP
Similar to Cabotegravir (Apretude), which provides 2 months of protection after a single shot.
Leronlimab has a long half-life (~10-14 days), meaning it could be formulated as a monthly or bi-monthly injection for HIV prevention.
Advantage: Unlike oral PrEP (which requires daily pills), an injection would be easier for adherence.
Option 2: Post-Exposure Prophylaxis (PEP)
Since Leronlimab blocks HIV entry, it could be a faster-acting alternative to traditional PEP (which requires 28 days of pills).
How It Would Work: Someone could get an emergency Leronlimab injection after exposure, preventing HIV from infecting immune cells.
Advantage: Could replace or enhance traditional PEP regimens.
Option 3: Combination PrEP
Leronlimab could be combined with other PrEP options, like integrase inhibitors or broadly neutralizing antibodies (bNAbs), for multi-layered protection.
Why? If Leronlimab also affects intracellular Ca²⁺ and TG2, it might block HIV even after initial exposure.
3. Challenges & Next Steps for Leronlimab as an HIV Preventative
Challenges
No PrEP-Specific Trials Yet
Leronlimab has been tested for HIV treatment, but not yet for prevention.
A formal PrEP study would need to test whether it prevents HIV infection in high-risk individuals.
CCR5-Only Protection
Leronlimab only works against CCR5-tropic HIV (~60-70% of new infections).
It wouldn’t protect against CXCR4-tropic HIV, so it might need to be combined with other drugs.
Regulatory & Market Barriers
FDA approval is needed specifically for PrEP, not just HIV treatment.
Competing long-acting PrEP options (like Cabotegravir) already exist, so Leronlimab would need a clear advantage to gain market adoption.
Next Steps
Phase 3 Trials for HIV Prevention → A study testing Leronlimab as a standalone PrEP option would be needed.
Combination Studies → Could Leronlimab + a capsid inhibitor (like Lenacapavir) offer dual-layer protection?
Exploring Ca²⁺ & TG2 Effects → If Leronlimab’s effects on intracellular Ca²⁺ and TG2 make cells less hospitable to HIV, it could enhance traditional PrEP.
Final Thoughts
Leronlimab is a strong candidate for HIV prevention, but it needs formal trials to prove its effectiveness as PrEP. If its Ca²⁺-modulating effects provide added viral resistance, it could offer a new approach beyond standard CCR5 blocking.
Would you like to dive deeper into any of these areas—like the biology of Ca²⁺ in HIV, existing PrEP alternatives, or potential clinical trial designs?
Yes
Diving Deeper: Leronlimab, Ca²⁺ Regulation, and HIV Prevention
Since you’re interested in how Leronlimab’s regulation of intracellular Ca²⁺ could affect HIV prevention, let’s break this down into three key areas:
The Role of Intracellular Ca²⁺ in HIV Infection
How Leronlimab’s Ca²⁺ Effects Could Inhibit HIV
Potential Clinical Applications & Next Steps
1. The Role of Intracellular Ca²⁺ in HIV Infection
HIV actively manipulates calcium (Ca²⁺) signaling inside host cells to enhance its infection and replication. Some key processes include:
HIV Entry & Fusion:
After binding to CCR5 or CXCR4, HIV triggers Ca²⁺ influx to facilitate membrane fusion and viral entry.
This Ca²⁺ signaling helps activate actin cytoskeleton remodeling, allowing HIV to enter immune cells.
HIV Replication & Viral Transcription:
Once inside, HIV hijacks Ca²⁺-dependent pathways to promote viral gene transcription.
The NFAT (nuclear factor of activated T cells) pathway, which depends on Ca²⁺ signaling, is used by HIV to enhance viral gene expression.
TG2 Activation & Immune Dysregulation:
Transglutaminase-2 (TG2) is activated by high Ca²⁺ levels.
TG2 plays a role in cell signaling, inflammation, and fibrosis, contributing to HIV-related immune dysfunction and tissue damage.
Thus, lowering intracellular Ca²⁺ could make it harder for HIV to enter, replicate, and persist in host cells.
2. How Leronlimab’s Ca²⁺ Effects Could Inhibit HIV
Leronlimab is already known to block CCR5, but if it also lowers intracellular Ca²⁺ levels, it could:
A. Block HIV Entry More Effectively
By downregulating Ca²⁺, Leronlimab might reduce the Ca²⁺ influx required for HIV fusion, making it harder for the virus to infect immune cells.
This could enhance its role as a PrEP option by making cells less susceptible to infection.
B. Suppress HIV Replication in Latent Reservoirs
Even if HIV gets inside, it needs Ca²⁺-regulated transcription factors (like NFAT) to reactivate.
Leronlimab’s Ca²⁺ effects could help keep HIV dormant, preventing viral rebound.
This could make it useful not just for prevention, but also for long-term viral suppression in people with HIV.
C. Reduce HIV-Induced Inflammation & Immune Exhaustion
Chronic HIV infection leads to inflammation and fibrosis, partly due to TG2 activation.
By lowering Ca²⁺, Leronlimab might reduce TG2 activation, leading to less immune dysfunction and tissue damage in long-term HIV infection.
3. Potential Clinical Applications & Next Steps
Clinical Trial Possibilities for HIV Prevention
A Phase 2/3 study could test whether Leronlimab alone prevents HIV infection in high-risk individuals (similar to Cabotegravir trials).
Trials could also measure Ca²⁺ levels and TG2 activity in people taking Leronlimab, to see if these effects contribute to HIV resistance.
Combining Leronlimab with Other PrEP Strategies
Leronlimab + Capsid Inhibitors (Lenacapavir) → This could provide both entry and replication blockade.
Leronlimab + bNAbs (Broadly Neutralizing Antibodies) → Could cover both CCR5-tropic and CXCR4-tropic HIV strains.
Leronlimab + Long-Acting PrEP (Cabotegravir) → Could enhance protection while reducing inflammation in the immune system.
Exploring Its Role in a Functional HIV Cure
If Leronlimab helps suppress latent HIV by lowering Ca²⁺, it could be tested in cure strategies, alongside CRISPR or latency-reversing agents.
Final Thoughts: Could Leronlimab Be a New Type of HIV Preventative?
CCR5 blockade alone is effective, but Leronlimab’s possible effects on Ca²⁺ and TG2 could give it extra advantages over existing PrEP drugs.
If it proves to inhibit HIV replication beyond just blocking entry, it could be explored as a next-generation HIV preventative & treatment enhancer.
More clinical trials are needed to confirm these effects, but if validated, Leronlimab could be a game-changer for HIV prevention and long-term suppression.
Would you like to discuss potential trial designs, alternative delivery methods (e.g., nasal sprays, implants), or comparisons with other CCR5 blockers (like Maraviroc)?
Yes
1. Potential Clinical Trial Designs for Leronlimab as an HIV Preventative
Since Leronlimab has already been tested for HIV treatment, the next step would be specific trials for prevention (PrEP). Here’s how these could be structured:
A. Phase 2/3 Trial for Leronlimab as a Standalone PrEP Option
Goal: Determine whether Leronlimab can prevent HIV infection in high-risk individuals.
Participants: HIV-negative people at high risk (e.g., MSM, sex workers, serodiscordant couples).
Design:
Group 1: Leronlimab injection every 4–8 weeks
Group 2: Current standard PrEP (Cabotegravir or Truvada)
Group 3: Placebo (to measure baseline risk)
Outcome Measures:
HIV infection rates over 1–2 years
Changes in Ca²⁺ levels & TG2 activity in immune cells
Long-term immune function and inflammation markers
✅ Why This Matters: If Leronlimab shows similar or better efficacy than existing PrEP, it could be a new option for people who can’t take daily oral PrEP or who need an alternative to integrase inhibitors (like Cabotegravir).
B. Combination Trial: Leronlimab + Other PrEP Options
Goal: Test whether Leronlimab + another drug (e.g., capsid inhibitors or bNAbs) provides better protection than a single drug alone.
Potential Combinations:
Leronlimab + Lenacapavir (Capsid Inhibitor) → Targets HIV entry + replication.
Leronlimab + bNAbs (Broadly Neutralizing Antibodies) → Blocks both CCR5- and CXCR4-tropic HIV strains.
Leronlimab + Cabotegravir (Long-Acting PrEP) → Dual-layer protection: prevents entry & viral integration.
Outcome Measures:
HIV prevention rates (compared to single-drug PrEP)
Effects on viral reservoirs & immune activation
Long-term tolerability & side effects
✅ Why This Matters: If Leronlimab works well in combination, it could be added to existing PrEP regimens to provide multi-layered protection.
2. Alternative Delivery Methods for Leronlimab PrEP
Right now, Leronlimab is being tested as an injectable, but other delivery methods could make it even more accessible:
A. Leronlimab Implants (Long-Lasting PrEP)
How It Works: A small implant (like the Nexplanon birth control implant) releases Leronlimab slowly over 6–12 months.
Why It’s Useful: No need for frequent injections or daily pills—perfect for people who struggle with adherence.
Example: Similar to the Islatravir implant (Merck’s experimental HIV prevention implant).
B. Leronlimab Nasal Spray (Mucosal HIV Protection)
How It Works: A nasal spray could coat mucosal tissues (e.g., rectal & vaginal tissue) with Leronlimab, blocking HIV at the first point of contact.
Why It’s Useful:
Works before exposure—could be used on-demand, like a “morning-after” HIV prevention option.
Faster absorption than injections.
Could be combined with bNAbs or microbicides to create a multipurpose HIV prevention gel/spray.
✅ Why This Matters: New delivery methods could make Leronlimab more convenient and expand its use beyond just high-risk populations.
3. How Leronlimab Compares to Other CCR5 Blockers (Like Maraviroc)
Maraviroc (Selzentry) is another CCR5 blocker that has been tested for HIV prevention. However, Leronlimab has some potential advantages:
Feature Leronlimab Maraviroc
Mechanism Blocks CCR5 (entry prevention) Blocks CCR5 (entry prevention)
Delivery Injectable (long-acting) Oral (daily pill)
Half-Life ~10–14 days (long-lasting) ~14 hours (short-acting)
Potential Ca²⁺ & TG2 Effects Yes (immune modulation, viral suppression?) No
Tolerability Fewer systemic side effects Some liver toxicity
Use in PrEP? Not yet tested Has been studied for PrEP but wasn’t widely adopted
✅ Why This Matters: If Leronlimab’s Ca²⁺-modulating effects provide additional immune benefits, it could offer stronger, longer-lasting protection than Maraviroc.
Final Takeaways & Next Steps
???? Leronlimab’s Ca²⁺-modulating properties could give it an advantage over existing PrEP options by reducing both HIV entry and viral persistence.
???? Clinical trials for PrEP are the next big step—if Leronlimab shows comparable or better protection than Cabotegravir, it could be a new long-acting PrEP option.
???? Exploring new delivery methods (implants, nasal sprays) could expand its use beyond high-risk populations, making it more accessible.
Would you like to explore funding possibilities for trials, regulatory challenges, or potential patient populations that could benefit most?
Maybe late, but thank you.
You're very welcome! No such thing as late—I'm always here to chat. If you ever want to dive deeper into any of this, just let me know. Hope you have a great day! ????????
This morning I spoke with my friend ChatGpt about your post earlier,
The transglutaminase-2 enzyme, here is the reply.
The transglutaminase-2 enzyme that it targets needs high levels of intracellular CA-2+ to activate. Leronlimab downregulates that CA-2+.
It sounds like you're discussing Leronlimab's mechanism in relation to transglutaminase-2 (TG2) and calcium (Ca²⁺) regulation. Leronlimab, a CCR5 antagonist, is primarily known for its immunomodulatory effects, particularly in reducing inflammation and blocking HIV entry into cells. If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation, since TG2 requires high Ca²⁺ concentrations to become active.
Are you looking for more details on how Leronlimab affects calcium signaling, TG2's role in disease, or something else?
If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation since TG2 requires high Ca²⁺ concentrations to become active. Could this be a cure for HIV
Leronlimab’s ability to downregulate intracellular Ca²⁺ could indeed have interesting implications for transglutaminase-2 (TG2) activity, but calling it a cure for HIV would be a big leap. Here’s why:
HIV Persistence & Reservoirs – A true cure for HIV would require eliminating or functionally silencing latent viral reservoirs. Leronlimab primarily blocks the CCR5 co-receptor, preventing new infections but not necessarily eradicating existing reservoirs.
TG2’s Role in HIV – TG2 has been implicated in inflammatory processes and fibrosis, particularly in HIV-related immune dysfunction. If Leronlimab reduces TG2 activation by lowering intracellular Ca²⁺, it might help mitigate HIV-associated inflammation and tissue damage, but this doesn’t mean it eradicates the virus itself.
Functional Cure vs. Sterilizing Cure – A functional cure means HIV is controlled without ART, while a sterilizing cure means the virus is completely eliminated. Leronlimab has shown promise in reducing viral load and inflammation, but there’s no evidence yet that it can fully clear the virus from the body.
Combination Strategies – Many believe a cure for HIV will require a combination approach: latency-reversing agents, immune-based therapies, and possibly gene-editing technologies like CRISPR. Leronlimab could be part of a broader strategy, but by itself, it’s unlikely to be a standalone cure.
If it downregulates intracellular Ca²⁺ levels, this could indirectly impact TG2 activation since TG2 requires high Ca²⁺ concentrations to become active. Could Leronlimab work as a contraceptive for HIV?
That’s an interesting angle! If Leronlimab downregulates intracellular Ca²⁺, and since transglutaminase-2 (TG2) activation depends on high Ca²⁺ levels, there could be an indirect impact on HIV’s ability to establish infection or persist. However, whether this mechanism would make Leronlimab an effective contraceptive for HIV transmission is another question.
Here’s what we know:
1. Leronlimab as an HIV Blocker
Leronlimab is a CCR5 antagonist, meaning it blocks the CCR5 co-receptor that many HIV strains (R5-tropic) use to enter immune cells.
This prevents new infections but doesn’t clear existing ones.
2. The Role of Calcium in HIV and TG2
HIV manipulates calcium signaling during infection, and Ca²⁺ levels play a role in viral replication and immune activation.
TG2 is involved in inflammation, immune responses, and potentially fibrosis in chronic HIV. If TG2 is less active due to reduced Ca²⁺, it might affect the local cellular environment in ways that impact HIV persistence or transmission.
3. Could This Prevent HIV Transmission?
A contraceptive for HIV (or a preventative method) would need to stop viral transmission at mucosal surfaces (vaginal, rectal, etc.).
Leronlimab primarily works inside immune cells, meaning it’s not directly a topical or systemic barrier against HIV entry like PrEP (e.g., Truvada, Descovy).
However, if its effects on intracellular Ca²⁺ significantly reduce HIV’s ability to infect new cells or establish reservoirs, there could be potential for preventing infection after exposure—similar to post-exposure prophylaxis (PEP).
4. Could Leronlimab Be Used for HIV Prevention?
As PrEP? Possibly, but current PrEP drugs work by preventing viral replication once HIV enters the body, not by targeting calcium signaling.
As a microbicide or topical gel? Unlikely, since its mechanism involves systemic immune cell interactions rather than direct mucosal protection.
Conclusion
Leronlimab’s ability to block CCR5 is already a strong preventive measure against HIV infection for R5-tropic strains. If its Ca²⁺-lowering effect further disrupts TG2 or other HIV-related pathways, it could enhance its antiviral properties. However, it wouldn’t function like a traditional contraceptive (such as a barrier or microbicide).
Would you like to explore whether Leronlimab could be used in combination with other HIV prevention methods?
Yes
Leronlimab could definitely be considered as part of a combination strategy for HIV prevention, but let’s break it down into different approaches to see how it might fit in:
Leronlimab could definitely be considered as part of a combination strategy for HIV prevention, but let’s break it down into different approaches to see how it might fit in:
1. Leronlimab + Existing PrEP (Pre-Exposure Prophylaxis)
Current PrEP drugs (Truvada, Descovy): These use tenofovir/emtricitabine to prevent HIV from replicating after entry.
How Leronlimab could help: Since it blocks the CCR5 receptor, it could complement PrEP by providing an additional layer of defense, especially against R5-tropic HIV strains.
Potential Benefit: This combo could reduce the chances of infection even further, especially for individuals at high risk.
2. Leronlimab as a Long-Acting Injectable for HIV Prevention
Current injectables like Cabotegravir (Apretude) offer long-lasting protection against HIV.
Leronlimab is already an antibody therapy, meaning it could be formulated as a long-acting injection.
Potential Benefit: If it’s shown to reduce intracellular Ca²⁺ and interfere with HIV’s replication machinery, it might provide sustained protection similar to or better than Cabotegravir.
3. Leronlimab + Microbicides or Topical Gels
Microbicides are gels or creams that can be applied to vaginal/rectal tissues to block HIV transmission.
If Leronlimab affects intracellular Ca²⁺, it might reduce the ability of HIV to infect local immune cells in mucosal tissues.
Potential Benefit: If it could be formulated into a gel or suppository, it could work as a mucosal immune modulator, reducing local inflammation and HIV susceptibility.
4. Leronlimab + PEP (Post-Exposure Prophylaxis)
PEP (like Truvada + Isentress) is taken after exposure to prevent HIV infection.
If Leronlimab lowers intracellular Ca²⁺, it might make cells less hospitable to viral replication, improving PEP’s effectiveness.
Potential Benefit: Faster immune response and reduced viral establishment in early infection.
Final Thoughts: Could Leronlimab Be a Standalone HIV Preventative?
For R5-tropic HIV: It’s already a strong candidate since it blocks CCR5.
For all HIV strains: It might need to be combined with other strategies.
Its impact on Ca²⁺ and TG2: If it significantly interferes with HIV replication or immune activation, it could enhance existing prevention methods.
Would you be interested in seeing how Leronlimab compares to other experimental HIV prevention strategies (e.g., vaccines, gene editing, etc.)?
Would you be interested in seeing how Leronlimab compares to other experimental HIV prevention strategies (e.g., vaccines, gene editing, etc.)?
Yes
There are several experimental HIV prevention strategies in development, and Leronlimab could potentially fit into this evolving landscape. Let’s compare it to other cutting-edge approaches:
1. Broadly Neutralizing Antibodies (bNAbs)
How They Work: These antibodies target multiple strains of HIV by blocking key viral proteins (e.g., CD4-binding sites on gp120).
Examples: VRC01, 3BNC117, 10-1074.
How Leronlimab Compares:
Leronlimab is an anti-CCR5 monoclonal antibody, meaning it prevents HIV from attaching to cells rather than directly neutralizing the virus.
If it has additional effects on intracellular Ca²⁺ and TG2, it could offer immune modulation beyond viral blocking.
2. Long-Acting Injectable PrEP (Cabotegravir, Lenacapavir)
How They Work: These drugs inhibit HIV replication (integrase inhibitors like Cabotegravir, capsid inhibitors like Lenacapavir).
How Leronlimab Compares:
Leronlimab works earlier in the infection process, blocking entry instead of replication.
If it can also lower intracellular Ca²⁺, it might disrupt HIV’s ability to establish infection, making it a potential addition to long-acting PrEP.
3. Gene Editing (CRISPR-based HIV Cure Strategies)
How They Work: CRISPR is being tested to cut out HIV genes from infected cells or modify genes to make humans resistant (e.g., CCR5 gene knockout).
Examples: Trials using CRISPR to edit the CCR5 gene, similar to the mutation found in the famous “Berlin Patient” and “London Patient” (who were cured after bone marrow transplants with CCR5 mutations).
How Leronlimab Compares:
Instead of permanently modifying CCR5, Leronlimab temporarily blocks it, making it a safer and more reversible approach.
Potential Combo? Leronlimab could be used alongside CRISPR to temporarily block CCR5 while gene-editing therapies take effect.
4. HIV Vaccines (mRNA & Other Approaches)
How They Work: Teach the immune system to recognize and attack HIV before infection.
Examples:
Moderna’s mRNA HIV vaccine (similar to COVID vaccines).
Mosaic vaccine trials (using adenovirus vectors).
How Leronlimab Compares:
Vaccines aim to train the immune system, while Leronlimab directly blocks infection.
If Leronlimab has long-term immune-modulating effects (via Ca²⁺ and TG2 pathways), it could complement vaccines by reducing inflammation and viral susceptibility.
5. Stem Cell & CAR-T Cell Therapy
How They Work:
Stem cell transplants with CCR5-deficient donor cells (e.g., “Berlin Patient”).
CAR-T cells engineered to kill HIV-infected cells.
How Leronlimab Compares:
Leronlimab is far less invasive than a transplant or gene therapy.
If it helps regulate intracellular Ca²⁺ and immune responses, it could reduce HIV-associated immune dysfunction, making it useful in combination with immune-based therapies.
Where Leronlimab Fits In
Short-Term Prevention: Leronlimab could be part of a long-acting PrEP strategy (similar to Cabotegravir).
Long-Term Strategies: It could work alongside CRISPR or stem cell therapies to help manage immune response and block infection while more permanent solutions take effect.
Combination Use: If its intracellular Ca²⁺ effects impact viral replication, it might enhance other HIV treatments or reduce chronic inflammation in long-term HIV patients.
Final Thought: Could Leronlimab Become a Game-Changer?
Leronlimab is already in clinical trials for HIV treatment and could have a role in prevention if further studies confirm its ability to disrupt Ca²⁺-mediated pathways important for HIV replication.
Would you like to explore any specific area further (e.g., clinical trial data, formulation as a PrEP option, etc.)?
Great! Let’s break it down further. Since you’re interested in Leronlimab’s potential as an HIV prevention option, we can look at:
Current Clinical Trial Data on Leronlimab for HIV
How Leronlimab Could Be Used for PrEP
Potential Challenges & Next Steps
1. Current Clinical Trial Data on Leronlimab for HIV
Leronlimab has been in clinical trials for HIV treatment rather than prevention so far. Some key takeaways:
Completed Trials (HIV Treatment)
Leronlimab + HAART (Highly Active Antiretroviral Therapy)
Showed reduced viral load in patients with multi-drug-resistant HIV.
Maintained viral suppression without severe side effects.
Monotherapy Trials (Leronlimab Alone)
Some trials tested Leronlimab as a standalone treatment for HIV.
It reduced viral load but wasn’t enough alone to maintain long-term suppression.
What This Means for HIV Prevention
Since Leronlimab effectively blocks CCR5-tropic HIV, it could work similarly to Maraviroc (another CCR5 blocker used for prevention & treatment).
However, there’s no official PrEP trial yet, meaning it hasn’t been tested specifically in people before exposure to see if it prevents infection.
2. How Leronlimab Could Be Used for PrEP (HIV Prevention)
If Leronlimab were tested for PrEP, here’s how it could fit in:
Option 1: Long-Acting Injectable PrEP
Similar to Cabotegravir (Apretude), which provides 2 months of protection after a single shot.
Leronlimab has a long half-life (~10-14 days), meaning it could be formulated as a monthly or bi-monthly injection for HIV prevention.
Advantage: Unlike oral PrEP (which requires daily pills), an injection would be easier for adherence.
Option 2: Post-Exposure Prophylaxis (PEP)
Since Leronlimab blocks HIV entry, it could be a faster-acting alternative to traditional PEP (which requires 28 days of pills).
How It Would Work: Someone could get an emergency Leronlimab injection after exposure, preventing HIV from infecting immune cells.
Advantage: Could replace or enhance traditional PEP regimens.
Option 3: Combination PrEP
Leronlimab could be combined with other PrEP options, like integrase inhibitors or broadly neutralizing antibodies (bNAbs), for multi-layered protection.
Why? If Leronlimab also affects intracellular Ca²⁺ and TG2, it might block HIV even after initial exposure.
3. Challenges & Next Steps for Leronlimab as an HIV Preventative
Challenges
No PrEP-Specific Trials Yet
Leronlimab has been tested for HIV treatment, but not yet for prevention.
A formal PrEP study would need to test whether it prevents HIV infection in high-risk individuals.
CCR5-Only Protection
Leronlimab only works against CCR5-tropic HIV (~60-70% of new infections).
It wouldn’t protect against CXCR4-tropic HIV, so it might need to be combined with other drugs.
Regulatory & Market Barriers
FDA approval is needed specifically for PrEP, not just HIV treatment.
Competing long-acting PrEP options (like Cabotegravir) already exist, so Leronlimab would need a clear advantage to gain market adoption.
Next Steps
Phase 3 Trials for HIV Prevention → A study testing Leronlimab as a standalone PrEP option would be needed.
Combination Studies → Could Leronlimab + a capsid inhibitor (like Lenacapavir) offer dual-layer protection?
Exploring Ca²⁺ & TG2 Effects → If Leronlimab’s effects on intracellular Ca²⁺ and TG2 make cells less hospitable to HIV, it could enhance traditional PrEP.
Final Thoughts
Leronlimab is a strong candidate for HIV prevention, but it needs formal trials to prove its effectiveness as PrEP. If its Ca²⁺-modulating effects provide added viral resistance, it could offer a new approach beyond standard CCR5 blocking.
Would you like to dive deeper into any of these areas—like the biology of Ca²⁺ in HIV, existing PrEP alternatives, or potential clinical trial designs?
Yes
Diving Deeper: Leronlimab, Ca²⁺ Regulation, and HIV Prevention
Since you’re interested in how Leronlimab’s regulation of intracellular Ca²⁺ could affect HIV prevention, let’s break this down into three key areas:
The Role of Intracellular Ca²⁺ in HIV Infection
How Leronlimab’s Ca²⁺ Effects Could Inhibit HIV
Potential Clinical Applications & Next Steps
1. The Role of Intracellular Ca²⁺ in HIV Infection
HIV actively manipulates calcium (Ca²⁺) signaling inside host cells to enhance its infection and replication. Some key processes include:
HIV Entry & Fusion:
After binding to CCR5 or CXCR4, HIV triggers Ca²⁺ influx to facilitate membrane fusion and viral entry.
This Ca²⁺ signaling helps activate actin cytoskeleton remodeling, allowing HIV to enter immune cells.
HIV Replication & Viral Transcription:
Once inside, HIV hijacks Ca²⁺-dependent pathways to promote viral gene transcription.
The NFAT (nuclear factor of activated T cells) pathway, which depends on Ca²⁺ signaling, is used by HIV to enhance viral gene expression.
TG2 Activation & Immune Dysregulation:
Transglutaminase-2 (TG2) is activated by high Ca²⁺ levels.
TG2 plays a role in cell signaling, inflammation, and fibrosis, contributing to HIV-related immune dysfunction and tissue damage.
Thus, lowering intracellular Ca²⁺ could make it harder for HIV to enter, replicate, and persist in host cells.
2. How Leronlimab’s Ca²⁺ Effects Could Inhibit HIV
Leronlimab is already known to block CCR5, but if it also lowers intracellular Ca²⁺ levels, it could:
A. Block HIV Entry More Effectively
By downregulating Ca²⁺, Leronlimab might reduce the Ca²⁺ influx required for HIV fusion, making it harder for the virus to infect immune cells.
This could enhance its role as a PrEP option by making cells less susceptible to infection.
B. Suppress HIV Replication in Latent Reservoirs
Even if HIV gets inside, it needs Ca²⁺-regulated transcription factors (like NFAT) to reactivate.
Leronlimab’s Ca²⁺ effects could help keep HIV dormant, preventing viral rebound.
This could make it useful not just for prevention, but also for long-term viral suppression in people with HIV.
C. Reduce HIV-Induced Inflammation & Immune Exhaustion
Chronic HIV infection leads to inflammation and fibrosis, partly due to TG2 activation.
By lowering Ca²⁺, Leronlimab might reduce TG2 activation, leading to less immune dysfunction and tissue damage in long-term HIV infection.
3. Potential Clinical Applications & Next Steps
Clinical Trial Possibilities for HIV Prevention
A Phase 2/3 study could test whether Leronlimab alone prevents HIV infection in high-risk individuals (similar to Cabotegravir trials).
Trials could also measure Ca²⁺ levels and TG2 activity in people taking Leronlimab, to see if these effects contribute to HIV resistance.
Combining Leronlimab with Other PrEP Strategies
Leronlimab + Capsid Inhibitors (Lenacapavir) → This could provide both entry and replication blockade.
Leronlimab + bNAbs (Broadly Neutralizing Antibodies) → Could cover both CCR5-tropic and CXCR4-tropic HIV strains.
Leronlimab + Long-Acting PrEP (Cabotegravir) → Could enhance protection while reducing inflammation in the immune system.
Exploring Its Role in a Functional HIV Cure
If Leronlimab helps suppress latent HIV by lowering Ca²⁺, it could be tested in cure strategies, alongside CRISPR or latency-reversing agents.
Final Thoughts: Could Leronlimab Be a New Type of HIV Preventative?
CCR5 blockade alone is effective, but Leronlimab’s possible effects on Ca²⁺ and TG2 could give it extra advantages over existing PrEP drugs.
If it proves to inhibit HIV replication beyond just blocking entry, it could be explored as a next-generation HIV preventative & treatment enhancer.
More clinical trials are needed to confirm these effects, but if validated, Leronlimab could be a game-changer for HIV prevention and long-term suppression.
Would you like to discuss potential trial designs, alternative delivery methods (e.g., nasal sprays, implants), or comparisons with other CCR5 blockers (like Maraviroc)?
Yes
1. Potential Clinical Trial Designs for Leronlimab as an HIV Preventative
Since Leronlimab has already been tested for HIV treatment, the next step would be specific trials for prevention (PrEP). Here’s how these could be structured:
A. Phase 2/3 Trial for Leronlimab as a Standalone PrEP Option
Goal: Determine whether Leronlimab can prevent HIV infection in high-risk individuals.
Participants: HIV-negative people at high risk (e.g., MSM, sex workers, serodiscordant couples).
Design:
Group 1: Leronlimab injection every 4–8 weeks
Group 2: Current standard PrEP (Cabotegravir or Truvada)
Group 3: Placebo (to measure baseline risk)
Outcome Measures:
HIV infection rates over 1–2 years
Changes in Ca²⁺ levels & TG2 activity in immune cells
Long-term immune function and inflammation markers
✅ Why This Matters: If Leronlimab shows similar or better efficacy than existing PrEP, it could be a new option for people who can’t take daily oral PrEP or who need an alternative to integrase inhibitors (like Cabotegravir).
B. Combination Trial: Leronlimab + Other PrEP Options
Goal: Test whether Leronlimab + another drug (e.g., capsid inhibitors or bNAbs) provides better protection than a single drug alone.
Potential Combinations:
Leronlimab + Lenacapavir (Capsid Inhibitor) → Targets HIV entry + replication.
Leronlimab + bNAbs (Broadly Neutralizing Antibodies) → Blocks both CCR5- and CXCR4-tropic HIV strains.
Leronlimab + Cabotegravir (Long-Acting PrEP) → Dual-layer protection: prevents entry & viral integration.
Outcome Measures:
HIV prevention rates (compared to single-drug PrEP)
Effects on viral reservoirs & immune activation
Long-term tolerability & side effects
✅ Why This Matters: If Leronlimab works well in combination, it could be added to existing PrEP regimens to provide multi-layered protection.
2. Alternative Delivery Methods for Leronlimab PrEP
Right now, Leronlimab is being tested as an injectable, but other delivery methods could make it even more accessible:
A. Leronlimab Implants (Long-Lasting PrEP)
How It Works: A small implant (like the Nexplanon birth control implant) releases Leronlimab slowly over 6–12 months.
Why It’s Useful: No need for frequent injections or daily pills—perfect for people who struggle with adherence.
Example: Similar to the Islatravir implant (Merck’s experimental HIV prevention implant).
B. Leronlimab Nasal Spray (Mucosal HIV Protection)
How It Works: A nasal spray could coat mucosal tissues (e.g., rectal & vaginal tissue) with Leronlimab, blocking HIV at the first point of contact.
Why It’s Useful:
Works before exposure—could be used on-demand, like a “morning-after” HIV prevention option.
Faster absorption than injections.
Could be combined with bNAbs or microbicides to create a multipurpose HIV prevention gel/spray.
✅ Why This Matters: New delivery methods could make Leronlimab more convenient and expand its use beyond just high-risk populations.
3. How Leronlimab Compares to Other CCR5 Blockers (Like Maraviroc)
Maraviroc (Selzentry) is another CCR5 blocker that has been tested for HIV prevention. However, Leronlimab has some potential advantages:
Feature Leronlimab Maraviroc
Mechanism Blocks CCR5 (entry prevention) Blocks CCR5 (entry prevention)
Delivery Injectable (long-acting) Oral (daily pill)
Half-Life ~10–14 days (long-lasting) ~14 hours (short-acting)
Potential Ca²⁺ & TG2 Effects Yes (immune modulation, viral suppression?) No
Tolerability Fewer systemic side effects Some liver toxicity
Use in PrEP? Not yet tested Has been studied for PrEP but wasn’t widely adopted
✅ Why This Matters: If Leronlimab’s Ca²⁺-modulating effects provide additional immune benefits, it could offer stronger, longer-lasting protection than Maraviroc.
Final Takeaways & Next Steps
???? Leronlimab’s Ca²⁺-modulating properties could give it an advantage over existing PrEP options by reducing both HIV entry and viral persistence.
???? Clinical trials for PrEP are the next big step—if Leronlimab shows comparable or better protection than Cabotegravir, it could be a new long-acting PrEP option.
???? Exploring new delivery methods (implants, nasal sprays) could expand its use beyond high-risk populations, making it more accessible.
Would you like to explore funding possibilities for trials, regulatory challenges, or potential patient populations that could benefit most?
Maybe late, but thank you.
You're very welcome! No such thing as late—I'm always here to chat. If you ever want to dive deeper into any of this, just let me know. Hope you have a great day! ????????
(9)
(1)Scroll down for more posts ▼
