This is the only publication I found in a quick search:
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.
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.
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-Cli...
I was thinking it would be something that helps the worn ligament grow back. That I would consider a real cure.
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.
> I was thinking it would be something that helps the worn ligament grow back. That I would consider a real cure.
As far as I can tell, that is what it does:
> The drug is based on a molecule he discovered while working at Pfizer, and can be delivered via a once-a-month EpiPen-style injection, where it restores protective processes to diseased joints and enables the regeneration of affected tissues. It works by blocking a compound that supports the nerve cells involved in transmitting pain signals to the brain.
This doesn't say it just blocks the pain, it says it directly affects the nerve cells involved in transmitting pain. Those nerve cells could also be responsible for other unpleasant things, like generally complaining and always being inflamed and inhibiting proper healing.
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.
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.
Reasoning: He does not come off as a person without sympathy, and without empathy, so I feel comfortable assuming he FEELS it when the downstream users of his discoveries achieve improvement in their life due to his "fighting" medical work.
A national general daily newspaper.
> Guessing that wasn’t the intention.
No guessing needed.
Therefore the article itself is slimy, it is overt, and you are reading it VIA a tech-blog.
The slimy idea COULD be valid if there is the belief that BECAUSE this article is linked by a tech-blog (HN), that it is a technical article. The OP, https://news.ycombinator.com/user?id=shoggouth could be the person you'd want to direct the critque at. However since the mandate of HN is not restricted to tech articles, merely interesting tech related stuff often with an entrepreneurial bent, it is appropriate.
So, not slimy in any way.
So, it restores lost tissue by numbing nerves? This makes no sense.
Wonder if it's just poor reporting or if there is something to this?
So it affects the nerves in a much more complex way than simple numbing and on top of that it also plays a part in regulating inflammation and auto-immune activity that may worsen arthritis and prevent the body from healing what it can.
And this is a gross oversimplification but it gets the function across a bit better than the article.
Isn't it weird how you can work on an inherently benevolent endeavour and then present the whole thing on a way that looks like you're trying to con people (and looks unscientific to boot). Marketing really is a scourge.
"It is hoped the drug — which is not a cure but will make the condition much less painful for sufferers — ..."
On leaving the company, he acquired the intellectual property [IP] rights from his former employer
A lot of people don't do this when they leave or are terminated. It doesn't usually succeed, but it's always worth at least making the attempt. (In this case, Pfizer gave him the IP rights to the molecule he discovered in exchange for a portion of his company.)
Now I'm at a point I would only be fine with saying this if I didn't have any issues after a prolonged interval.
That's not it at all. Read the article.
It is one of my biggest pet peeves seeing folks with "good intentions" spout off about nonsense "cures" for a suite of currently chronic conditions. There are specific gene therapies being researched that _may_ remove the need for heavy medications at _some_point_ in the next decade, but the damage done by the disease will still require joint replacement surgeries etc.
Most competent people I've met have zero sense of humor when it comes to this area of research, and would have also fired anyone that mistakes pain medication for a "cure" (unless I misunderstood the press release gibberish.)
Have a great day, and please consider starting a fact-checking wiki like snopes to document the ignorant new age nonsense people perpetuate. =3
(Not sure if I have arthritis but really sore hips and lower back.)
I'm intolerant of a milk protein. I can handle the bathroom consequences, I can't handle the lower back consequences.
For more than just anecdotes you can go to the data/studies; pubmed.gov is a great resource for finding studies: https://pubmed.ncbi.nlm.nih.gov/?term=arthritis+diet
There is also nutritionfacts, which takes a science and clinical study based approach to look at how diet plays a role in a whole host of diseases and conditions: https://nutritionfacts.org/?s=arthritis
* nutritionfacts and Dr. Greger do have several vocal opponents however, so I encourage you to read the studies themselves and come to your own conclusions
Now there are foods that make it worse: generally anything with high sodium like pizza, fries, fast-food/restaurant food (Chinese food especially). Caffeine also makes it slightly worse. By far the worst of them all is alcohol though. After the alcohol wears off, I'm in so much agony that I can barely walk.
What does "processed foods" mean? Do you eat raw food that isn't combined in any way?
It's hard to draw a hard line but with common sense you can figure it out.
(They were already eating very "clean": little meat, no refined sugar, no refined starches, very little vegetable oils)
Dairy, as I understand it, is highly inflammatory. Arthritis is some form of inflammation.
I had read that fatty fishes were a good source to reduce pain but in your experience, is there any other food/lifestyle changes that can help alleviate it before resorting to medication?
It has helped my mom who’s 74 (and has had it since early 50’s) significantly to the point where pain is mostly gone and inflammation is rare. It took about half a year for symptoms to be mostly gone. While it was my idea her doctor signed off on high dose (6000% typical daily allowance) prescription supplements considering the practically non-existing risk. Two years on and it’s stable and her life is a lot better.
Taking too much vitamin D can lead to hypercalcemia, which is an excess of calcium in the blood. This can cause symptoms such as:
Nausea and vomiting
Weakness and fatigue
Confusion and disorientation
Abnormal heartbeat
Kidney damage (in severe cases)
Long-term excessive intake can also increase the risk of kidney stones and other health problems.
Osteoarthritis is not an immune disorder.
https://nutritionfacts.org/video/why-do-plant-based-diets-he...
Long-term sufferers of RA - and the people in their support networks - know first-hand that RA is a complex and progressive condition that requires some pretty hardcore medical interventions to manage. Like other auto-immune diseases, different people will experience different disease courses. A very small few will be lucky enough that their disease goes into remission for no clear reason. Others will try everything under the sun only to see their disease become worse and worse. The reality for sufferers is that there aren't quick fixes and simple triggers.
It's reasonable to expect that general lifestyle interventions such as healthier diet and the right type of exercise regime may improve symptoms within the margins permitted by the underlying disease process. But promoting content that centers the role of "lifestyle" once RA has already developed only trivializes the disease and widens the empathy gap that sufferers already face.
In my experience, removing sugar has helped. Tumeric and Glucosamine have been known to help with anti inflammatory ailments. My sister in law takes bone broth and it has helped a lot with issues.
Does stress play a role in flare-ups for you? A family member has this, and aside from joint shocks .. kicking a thing too hard resulting in knee flare ups .. his stress level impacts his flare ups. E.g. "This thing in my life is going badly and I cannot escape it." .. when he does escape it, there are fewer flare-ups. ?
Eat foods in a way that can ignite ketosis periodically throughout the month and treat carbs as it's something your allergic to. I have personally (finally after 7 years) started regulating my cluster headaches which is an inflammation problem.
Cause or "is correlated with"?
I know that spinach (and other high oxalate foods) should not be eaten more than once or twice per week.
I do ketovore but for other reasons.
What this means is a lot of cooking from scratch, which means hands! So how about a whole food, plant based diet that requires very little preparation?
This is serious, so please do not waste time with 'cut out teh carbz' bro science. Do not take advice from anyone that talks of 'seed oils' and other keto talking points. Keto and carnivore diets are fad diets that are just another way to get to calorie restriction. They are popular amongst people with protein obsessions and social media influencers, because who does not want to eat steak and butter?
The whole food, plant based diet means no animal products, no refined sugars, no processed foods and lots of plants. Lots is important as vegetables, pulses, grains, beans and fruit are not as calorie dense as a lump of meat. You will need to be eating huge bowls of cooked food and not skipping meals just so you can get your calories in.
On a whole food, plant based diet, you can vary your diet by the season. This means buying from the vegetable and fruit aisles, going for whatever is on offer.
Due to the hands, you might want to buy lots of prepared frozen vegetables. Get the lot.
Oils are what you don't want in your system. Clearly we need some fats but there are plenty in nuts. Personally I only use a small amount of mild olive oil in the air fryer, I don't have butter or fake spreads.
Sugar is surprisingly easy to give up and comes with immediate health benefits as you have to home cook everything to avoid sugar. Sugar is in sauces and other savoury products that you would not expect.
Once you have knocked off sugar, you can knock off the animal products and expand your repertoire of goto plant based recipes.
What works for me is slow cooking. I usually start by putting a chopped onion and some garlic in the pot, to then add some starchy vegetables such as sweet potato, then some leafy greens, then a tonne of lentils and dried beans.
If there is room I put even more vegetables in and add some herbs and spices. Sometimes this could be a curry, or it could be a new herb I am experimenting with. Ginger goes in quite often, there is no fixed recipe as recipes are boring.
I usually add some chopped tomatoes, top up with water and set the thing to do its thing for about four hours.
This approach means I am spending twenty minutes in the kitchen every day, in total. I often add grains such as rice or barley, or I add pasta to the pot after taking my first portion, adding water as appropriate. Grains or pasta does not take four hours, an hour should be good. This means my second portion is a variation on the first.
To top out my slow cooked creation I put some tofu or even some vegetables such as broccoli in the air fryer, with some herbs. This gives different texture.
Just by varying the ingredients I can get variety even though I am doing a one pot meal.
Be an autodidact with this, implement your changes on a monthly basis and see how the inflammation in your hands changes. If you go WFPB then you should end up with excellent gut health, to be in the middle of the Bristol Poo Scale every time, with farts that don't smell.
This is an elimination diet, specifically sugar and animal products. Once you have done the 'factory reset' then you can add in the favourites again, super sensitive to how you feel afterwards. Or you might not want to. I could not care for sugar when it was gone, and the same with dairy, which I thought I was wedded to.
One pot meals, tray bakes and air fried things provide enough variety for me. I don't indulge in salads because of the lack of calories, and neither do I make smoothies because they are for babies, gym bros and people in care homes. Cooking is our original innovation and we need cooked food, mostly starches, to get the calories in.
I wouldn't be so confident in publicly discouraging my fellow human beings from trying these diets.
Speaking personally, I tried various diets -- raw milk diet (drinking 4L of raw milk a day), vegan diet, fruitarian diet, keto diet, caloric restriction, etc. -- before discovering that the carnivore diet helped my own condition (induced by antibiotic abuse), and I wrote about it here: https://srid.ca/carnivore-diet
Diets are personal; people should experiment and find out for themselves. In the long term, therapies like FMT should become widely available, enabling many of us to eat a wider range of food stuff.
Sad to see your informative and insightful comment modded down. Just goes to show how problematical discussion of all this can be. The issue is not so much ignorance as decades of (often profit-driven) misinformation. Peter C Gøtzsche wrote some books on problematical issues with a profit-driven medical industry.
Some more comments on related issues -- pardon if you have seen much of this before.
On your last paragraph, for salads, Dr. Joel Fuhrman suggests "Make the salad the main dish" including by adding a lot of things to it, like chickpeas and so on, and making dressing using nut butters. https://info.drfuhrman.com/make-salad-the-main-dish
He's also big on smoothies, especially in the morning, where people can drink them on the go.
I did not see you mention mushrooms. Something to consider: https://www.drfuhrman.com/blog/237/g-bombs-the-anti-cancer-f...
As a rule of thumb, Dr. Fuhrman basically suggests eating one pound raw foods and one pound cooked foods per day (ideally all WFPB). I can't say I manage that though. I keep trying to take short-cuts to all this, and probably none of them work that well. I've also tried meal delivery services (like Whole Harvest) but the cost, packaging, timing, and not having recipes tuned to my tastes is problematical -- even if the food is generally healthy otherwise. I am at least eating a lot more leafy greens, often in wraps -- although what I use for wraps can be problematical (any of processed wheat wraps, Ezekiel wraps, corn tortilla wraps, Nori wraps, large leaf lettuce, some worse than others).
Right now I am struggling with what to eat for breakfast. I have been trying some organic oat-based cereal with almond milk, fruit, and an organic plant-based protein powder -- but I know it could probably be much better if I was cooking more. Related to that I have been doing roughly 8:16 intermittent fasting by shifting my eating window into the mornings from roughly about 8am to 4pm (after a seven day water-only fast a couple months ago). So a good breakfast becomes more important. Surprised no comments by anyone here so far have mentioned fasting as another possible way to help with arthritis and other autoimmune issues.
The book "The Pleasure Trap" explains why so many people (whether me or your relative mentioned in your followup) are caught up in a "Pleasure Trap" of unhealthy eating related to how our natural inclinations rooted in food scarcity are maladapted for a world of food abundance (especially an abundance of salt, sugar and fat found in engineered ultraprocessed foods -- and also various non-food-related stress where the natural human response to stress is to fatten up for likely hard times):
https://www.healthpromoting.com/the-pleasure-trap
https://archive.org/details/the-pleasure-trap-mastering-the-...
Joe Cross' movie "Fat, Sick and Nearly Dead 2" explores why it can be so hard to keep up with healthy eating in modern Western society: https://www.rebootwithjoe.com/watch-here/
From: https://www.rebootwithjoe.com/about-fat-sick-nearly-dead-2/ "But then a funny thing happened, even with all the knowledge I’d learned, the techniques and tips I’ve gotten from experts, the fact that I was still off all of my medication, I found it was an ongoing struggle to keep the weight off! I was like, “hey, this isn’t supposed to be happening!” I’d done all the hard work, I even got off my meds! But that’s not how it works. I learned that losing the weight was easy, that the hard work really starts when you’re trying to maintain the weight loss. I quickly realized that I wasn’t alone. Seems like everyone has trouble keeping the weight off. That’s where the idea for “Fat, Sick & Nearly Dead #2” came from. I figured that I might as well share all this stuff. I was learning? So while I traveled to 10 countries, learning about health and nutrition along the way, I brought along the camera crew and what I found out is what you’ll see in the film. I visited doctors like Dean Ornish who gave me insight into the keys to health besides food, and Sheila Kar who gave me a view of my own arteries. A real eye-opener, I’ll tell you! I also wanted to know the power of marketing and see if I could eat only what I wanted to, not what I was being told to eat. That was what led me to Professor Brian Wansink who took me on a very enlightening tour of his hometown and showed me how food is sold to us and what we can do about it."
One interesting thing I read on Dr. Fuhrman's site somewhere is that one patient concluded it was cheaper to spend a month at a retreat and learn to eat better to reverse his heart disease than it would be to pay the deductible and copays on a heart bypass operation. I can wish there were more such health retreats all over the USA and the world -- maybe a Y-Combinator success yet to happen about that someday? https://www.drfuhrman.com/etlretreat
Supper clubs are one alternative to "retreats": "Logical Miracles: 100 Stories of Hope and Healing" https://www.amazon.com/Logical-Miracles-Stories-Hope-Healing... "Why is it so hard to eat right? What does it take to turn around the habits that make us sick and fat? Logical Miracles is a collection of stories by people in The Suppers Programs who found their personal solutions by experimenting with whole food. In an environment of nonjudgment, we cook, taste, and feel our way to health, and we forge new friendships based on healthy living. For five years, pilot Suppers groups have been helping people with a range of food-related challenges find their path, especially people with depression, anxiety, learning issues, obesity, diabetes, and problems with alcohol. No special diets. No fees. No commercial messages. The only requirement for membership is the desire to lead a healthier life. Now we’d like to share our logical miracles, our road maps, our recipes, and especially our hard-earned wisdom related as stories of hope and healing. Welcome to Suppers."
A bigger societal-level approach to transformation towards health is pursued by the "Blue Zones" project. https://www.bluezones.com/
Congrats on finding things that work for you to stay healthy in our current short-term-profit-maximizing society -- one that often privatizes gains like from addictive ultra-processed foods while socializing costs like ill health (paid for by higher medical-related taxes/borrowing and higher "health"-insurance premiums, not to mention years of personal suffering or family/communal grief from early deaths).
That is, if it's only suppressing pain, the people suffering will do more things that may cause more cartilege damage. (disclaimer: I don't know much about arthritis so I may be wrong)
I’ve had osteoarthritis in my knees since I was 16. At 27 I was opened up and told I had worn grooves through the cartilage and into the bone (I guess that’s why it hurt to ride a bike).
Doc told me quite literally to sit on a couch. Instead I took up karate, and the enforced stretching there relieved a ton of the pain. It didn’t fix anything, and i’d still get knee pain when riding a bike (I cut way back) or running, but my every day experience was tolerable.
In the past few years I started going to a functional fitness gym, and our coach got me towing a sled backwards- THAT fixed up my knees. Something about it has let my knees repair, and I haven’t had knees that felt this good sinc3 at least 1990.
I don't have a diagnosis for arthritis, but I'm testing around a lot and maybe this info helps you in your journey:
I make gelatine from pig's feet occasionally, when I make it with just salt and some lemon or vinegar, I don't have problems.
Last time I thought, maybe try bell pepper, haven't tried for a while and I seem to do okay with capsaicin. Boy was I wrong, within a week I got horrible joint pain in the feet.
Bell peppers are seemingly high in lectin and other phyto-nutrients.
I recently found on hacker news, that I can neutralize oxolates with a pro-biotic - will try that for lectins next. Have to prepare the gut with L-Glutamine and Silicea.
God's speed!
Edit: Between ingestion and symptoms, it takes about 3-4 days
Very interesting. Have you tried consuming beef liver to see if that helps? I was able to completely stop my VitD supplements after consuming liver.
Thinks can go wrong in Phase III.
Relyvrio (HIV vaccine) did well in P2 but flopped on P3.
Cancer drug xevinapant failed in P3 after Merck executives were reassuring analysts that the failure of a phase 3 trial of xevinapant was “unlikely.”
My rheumatologist wanted to put me on methotrexate but I declined out of fear if the side effects. He never mentioned anything about diet, but clearly a dietary intervention worked for me.
This looks more promising: https://www.youtube.com/watch?v=pQ1CLtc8oIk
Many times, I met people who genuinely believed they were super close and about to achieve a "huge" breakthrough.
In each case, the scientists themselves, in their minds, were absolutely convinced they were on the brink of unfathomable achievements: curing Alzheimers, or some cancers etc.
Particularly true for the scientists in biomedical startups - they were like Mulder from X-Files; they all wanted (and were desperately eager) to believe. Like Elizabeth Holmes of Theranos, I think she completely believed her own exaggerations and BS - at some point, fact and fiction merge.
Thus I've become extraordinarily skeptical of articles like these.
More like Pfizer invested in an employee's startup.
> The drug is based on a molecule he discovered while working at Pfizer
tells me that he'd better have good lawyers on speed-dial.
[EDITED TO ADD] It’s really common for large corporations, with staff counsel, to lodge lawsuits they know they can’t win, because they bet their pockets are deeper, and they think they can force a settlement.
Ugly, but it’s the American way. He may have more luck in the UK, though.
Yeah, I don't feel so bad for assuming.
The timeline is that you replied 4 days ago to the original thread, then 3 days later continue to try enage in arguments with me in another thread. Did you spend those three days festeringly mad and couldn't help but go in for round three?
If I made sure every paywalled link posted here had a paywall workaround linked in the comments, would that make you more mad? The FAQ says those links are allowed, but what are your personal feelings on it?
Yes, I guess you could belittle that by calling it 'a painkiller'. No different at all to taking a handful of ibuprofen, which every arthritis sufferer knows enables regeneration and why it is a solved problem.
It's another thing to read, as we have here, a title that proclaims 'This is a Pipe' to an article that states 'This is not a pipe'
If it weren't a similar story with so many 'medical breakthrough' headlines, it would annoy less.
> The drug is based on a molecule he discovered while working at Pfizer, and can be delivered via a once-a-month EpiPen-style injection, where it restores protective processes to diseased joints and enables the regeneration of affected tissues. It works by blocking a compound that supports the nerve cells involved in transmitting pain signals to the brain.
The mechanism might be to affect the nerve cells involved in pain signaling, but the effect is to actually help regenerate tissue.
This needs some heavy scrutiny, it seems like this is related to tanezumab. Which yes, blocks pain by affectively sticking a lego in front of another lego that when connected says hey I'm hurt, but doesn't pro-actively heal anything as far as I'm aware.
The usual play with claims like this is that with reduced inflammation there might be a better chance of circulation allowing for better natural regeneration (somewhat true?). But active regeneration of damaged tissue especially in places typically afflicted with athritis is a bit more complex because it's often at osteochondral boundry layers aren't as vascularized.
> It is hoped the drug — which is not a cure but will make the condition much less painful for sufferers [...]The “cure” for osteoarthritis would need to regenerate or replace damaged or missing cartilage, a seemingly impossible task from my limited understanding.
Patient don't care about having cartilage or bone sclerosis or subchondral cyst formation; they care about pain that stops them moving (which in turn can increase their weight further exacerbating the joint issues).
So, osteoarthritis is a problem in that it causes pain. If something specifically reduces osteoarthritic pain, I am okay with it saying it 'beats' the dis-ease.
I am merely explaining what the issue at hand is - I am not saying that is what the proposed medicine does. Another way to say it, is the compound treating the symptom or the problem - or perhaps both.
Imagine you have a hernia that hurts and you take medicine that masks that pain, do you still have hernia?
Edit: yup - https://web.archive.org/web/20240811063000/https://www.theti...
> It works by blocking a compound that supports the nerve cells involved in transmitting pain signals to the brain.
Unfortunately it doesn't fix the underlying issue.
I can see Pfizer lawyers salivating uncontrollably after reading that phrase. Extremely unwise of him to mention this.
> On leaving the company, he acquired the intellectual property [IP] rights from his former employer
Additional info: https://www.fiercebiotech.com/biotech/british-biotech-levice...
Is Pharma different than Engineering in terms of IP?
If my former employer has evidence that what I am working on in a new gig was discovered while on company time using company resources couldn't they sue?
> On leaving the company, he acquired the intellectual property [IP] rights from his former employer…