6 ms·

My only commentary would be that these results do not read like clinical success, but rather something suggesting they should move on to phase III clinical tria

My only commentary would be that these results do not read like clinical success, but rather something suggesting they should move on to phase III clinical trials. This is the only publication I found in a quick search: https://pubmed.ncbi.nlm.nih.gov/37976118/ https://pubmed.ncbi.nlm.nih.gov/37976118/ >> Abstract Objectives: Nerve growth factor β (β-NGF) is a protein which is important to the development of neurons particularly those involved in the transmission of pain and is central to the experience of pain in osteoarthritis (OA). Direct NGF antagonism has been shown to reduce OA pain but is associated with rapidly progressive OA. The aim of the study is to investigate the ability of soluble neurotrophin receptors in the NGF pathway to modulate pain in OA. Methods: Synovial fluid (SF) was obtained from the knee joints of 43 subjects who underwent total knee arthroplasty. Visual analogue scale (VAS) pain scores were obtained prior to surgery. Customised-automated-ELISAs and commercial-ELISAs and LEGENDplex™ were used to measure soluble low-affinity nerve growth factor (LNGFR), soluble tropomyosin receptor kinase (TrkA), proNGF, β-NGF, other neurotrophins (NT) and cytokines including inflammatory marker TNF-α. Results: The VAS score positively correlated with β-NGF (r=0.34) and there was positive association trend with neurotrophin-3 (NT-3), BDNF and negative association trend with ProNGF. sLNGFR positively correlated with VAS (r=0.33). The β-NGF/soluble TrkA ratio showed a strong positive correlation with VAS (r=0.80). In contrast, there was no correlation between pain and the β-NGF/sLNGFR ratio (r=-0.08). TNF-α positively correlated with β-NGF (r=0.83), NT-3 (r=0.66), and brain-derived neurotrophic factor (BDNF) (r=0.50) and negatively with ProNGF (r= -0.74) and positively correlated with both soluble TrkA (r=0.62), sLNGFR (r=0.26). Conclusions: This study suggests that endogenous or cleaved sLNGFR, but not soluble TrkA may participate in OA pain modulation thus supporting further research into soluble LNGFR as a therapeutic target in OA.

papercrane 2y ago
This is the Phase II clinic study: https://clinicaltrials.gov/study/NCT05618782 https://clinicaltrials.gov/study/NCT05618782 They haven't posted the results yet. They have posted a press release saying the results were positive and that they will post the results in a peer reviewed journal. https://levicept.com/wp-content/uploads/2024/08/Levicept-Clinical-Trial-Results-final-for-distribution-6-August-2024.pdf https://levicept.com/wp-content/uploads/2024/08/Levicept-Cli...
ramraj07 2y ago
It’s phase 2, not peer review published yet but results are out -https://www.morningstar.com/news/globe-newswire/1000985090/levicept-announces-positive-results-of-phase-ii-trial-of-novel-neurotrophin-3-inhibitor-levi-04-for-the-treatment-of-patients-with-moderate-to-severe-osteoarthritis https://www.morningstar.com/news/globe-newswire/1000985090/l... Sounds significant. Phase II is typically not enough to tell if a drug is good because most drugs aren’t that effective compared to current standard of care- you need the large numbers of phase iii to see the real difference. But looks like this drug shows a marked improvement in phase ii itself so it’s actually quite impressive. Last time I read such a story was for imatinib. Expecting good things from this.
deamanto 2y ago
Interesting - this looks like Beransa[1] (Librela) which is a monthly injection for canines that have osteoarthritis. My dog did not have any noticeable changes to pain after using this for 2 months so I've decided to take him off of it. [1] - https://en.wikipedia.org/wiki/Bedinvetmab https://en.wikipedia.org/wiki/Bedinvetmab
- bittercynic 2y ago
  I thought the same. My dog's been on it since last October, and it's made a big difference for him. Sorry to hear that it didn't help yours. I've been wondering how long it would be before something similar was available for humans.
  - deamanto 2y ago
    That's great that it works for him On the bright side, I also have mine on Pentosan which did have a noticeable difference for him so that's great https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs
- dl9999 2y ago
  When my dogs were alive, they had ketamine shots once a month (I think) and that seemed to help quite a bit.
- zukzuk 2y ago
  My cat has been in the feline equivalent (Solensia/frunevetmab) for about two years, and although it had a huge positive impact for the first 12 to 18 months, it seems to have suddenly completely stopped working in the last little while. One theory is that the immune system eventually starts attacking the monoclonal antibody med itself, another is that as in humans, the OA progression might accelerate under the drug.
  - deamanto 2y ago
    I also have mine on Pentosan which did have a noticeable difference for him so that's great. You could possibly talk to your vet about this, it's significantly cheaper than Beransa (110AUD/month) and for my dog it's biannual with a booster shot in between I actually (anecdotally) heard a similar issue with Pentosan that it stops working after 12-24 months due to the immune system so you have to "time it" at an appropriate time in a dog's life. To be blunt, by appropriate I mean you'd want to start using it 12-24 before the dog is expected to pass and not at the first sign of osteoarthritis. https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs
vjk800 2y ago
It sounds like, even in the best case scenario, the drug doesn't really cure arthritis but just blunts the pain. I was thinking it would be something that helps the worn ligament grow back. That I would consider a real cure.
- j45 2y ago
  Agree. Pain management is an important quality of life topic too
- datameta 2y ago
  The thing with chronic pain is that often it is garbage data being sent by pain receptors. Or more accurately our muddled processing of the nerve impulses leads to poorly established thresholds that lead to a constant presence of perceived pain. So preventing this pathology based on my experience is a cure. Physical regeneration is a separate target in my opinion.
- pdfernhout 2y ago
  A cure for much arthritis is possibly a Nutritarian Diet promoted by Dr. Joel Fuhrman which reduces inflammation and helps the body rebuild: https://www.drfuhrman.com/blog/119/a-progressive-approach-to-rheumatoid-arthritis https://www.drfuhrman.com/blog/119/a-progressive-approach-to... "The traditional treatment of rheumatoid arthritis revolves around medications which typically include steroids and chemotherapeutic agents such as methotrexate, Imuran®, Gold®, Plaquenil®, Arava® and Remicade®. These medications are considerably toxic and can result in serious disability. My approach to treating rheumatoid arthritis differs in that it incorporates dietary modifications and nutritional supplements, avoiding the use of toxic drugs in the vast majority of cases. The recommendations are customized to the needs and response of each patient to treatment and involve more than just putting them on a special diet. However, in most cases, dramatic improvements and even complete recoveries occur. In spite of well-conducted scientific investigations and the clinical experience of many physicians, this effective nutritional treatment of autoimmune disease is generally ignored. I have seen scores of patients with rheumatoid arthritis as well as lupus, fibromyalgia and connective tissue disease obtain complete recoveries through these natural interventions. Also, I have many patients who have made complete recoveries from allergies and asthma. Not every patient obtains a complete remission, but the majority is able to avoid the use of medication." The big problem in our current society is that there is no substantial money to be made by big companies in promoting these sorts of cures.

papercrane 2y ago

This is the Phase II clinic study: https://clinicaltrials.gov/study/NCT05618782 https://clinicaltrials.gov/study/NCT05618782 They haven't posted the results yet. They have posted a press release saying the results were positive and that they will post the results in a peer reviewed journal. https://levicept.com/wp-content/uploads/2024/08/Levicept-Clinical-Trial-Results-final-for-distribution-6-August-2024.pdf https://levicept.com/wp-content/uploads/2024/08/Levicept-Cli...

ramraj07 2y ago

It’s phase 2, not peer review published yet but results are out -https://www.morningstar.com/news/globe-newswire/1000985090/levicept-announces-positive-results-of-phase-ii-trial-of-novel-neurotrophin-3-inhibitor-levi-04-for-the-treatment-of-patients-with-moderate-to-severe-osteoarthritis https://www.morningstar.com/news/globe-newswire/1000985090/l... Sounds significant. Phase II is typically not enough to tell if a drug is good because most drugs aren’t that effective compared to current standard of care- you need the large numbers of phase iii to see the real difference. But looks like this drug shows a marked improvement in phase ii itself so it’s actually quite impressive. Last time I read such a story was for imatinib. Expecting good things from this.

deamanto 2y ago

Interesting - this looks like Beransa[1] (Librela) which is a monthly injection for canines that have osteoarthritis. My dog did not have any noticeable changes to pain after using this for 2 months so I've decided to take him off of it. [1] - https://en.wikipedia.org/wiki/Bedinvetmab https://en.wikipedia.org/wiki/Bedinvetmab

bittercynic 2y ago
I thought the same. My dog's been on it since last October, and it's made a big difference for him. Sorry to hear that it didn't help yours. I've been wondering how long it would be before something similar was available for humans.
- deamanto 2y ago
  That's great that it works for him On the bright side, I also have mine on Pentosan which did have a noticeable difference for him so that's great https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs
dl9999 2y ago
When my dogs were alive, they had ketamine shots once a month (I think) and that seemed to help quite a bit.
zukzuk 2y ago
My cat has been in the feline equivalent (Solensia/frunevetmab) for about two years, and although it had a huge positive impact for the first 12 to 18 months, it seems to have suddenly completely stopped working in the last little while. One theory is that the immune system eventually starts attacking the monoclonal antibody med itself, another is that as in humans, the OA progression might accelerate under the drug.
- deamanto 2y ago
  I also have mine on Pentosan which did have a noticeable difference for him so that's great. You could possibly talk to your vet about this, it's significantly cheaper than Beransa (110AUD/month) and for my dog it's biannual with a booster shot in between I actually (anecdotally) heard a similar issue with Pentosan that it stops working after 12-24 months due to the immune system so you have to "time it" at an appropriate time in a dog's life. To be blunt, by appropriate I mean you'd want to start using it 12-24 before the dog is expected to pass and not at the first sign of osteoarthritis. https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs https://en.wikipedia.org/wiki/Pentosan_polysulfate#Dogs

vjk800 2y ago

It sounds like, even in the best case scenario, the drug doesn't really cure arthritis but just blunts the pain. I was thinking it would be something that helps the worn ligament grow back. That I would consider a real cure.

j45 2y ago
Agree. Pain management is an important quality of life topic too
datameta 2y ago
The thing with chronic pain is that often it is garbage data being sent by pain receptors. Or more accurately our muddled processing of the nerve impulses leads to poorly established thresholds that lead to a constant presence of perceived pain. So preventing this pathology based on my experience is a cure. Physical regeneration is a separate target in my opinion.
pdfernhout 2y ago
A cure for much arthritis is possibly a Nutritarian Diet promoted by Dr. Joel Fuhrman which reduces inflammation and helps the body rebuild: https://www.drfuhrman.com/blog/119/a-progressive-approach-to-rheumatoid-arthritis https://www.drfuhrman.com/blog/119/a-progressive-approach-to... "The traditional treatment of rheumatoid arthritis revolves around medications which typically include steroids and chemotherapeutic agents such as methotrexate, Imuran®, Gold®, Plaquenil®, Arava® and Remicade®. These medications are considerably toxic and can result in serious disability. My approach to treating rheumatoid arthritis differs in that it incorporates dietary modifications and nutritional supplements, avoiding the use of toxic drugs in the vast majority of cases. The recommendations are customized to the needs and response of each patient to treatment and involve more than just putting them on a special diet. However, in most cases, dramatic improvements and even complete recoveries occur. In spite of well-conducted scientific investigations and the clinical experience of many physicians, this effective nutritional treatment of autoimmune disease is generally ignored. I have seen scores of patients with rheumatoid arthritis as well as lupus, fibromyalgia and connective tissue disease obtain complete recoveries through these natural interventions. Also, I have many patients who have made complete recoveries from allergies and asthma. Not every patient obtains a complete remission, but the majority is able to avoid the use of medication." The big problem in our current society is that there is no substantial money to be made by big companies in promoting these sorts of cures.