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Ubenimex (bestatin) treats lymphedema in mice. Will the drug help you?

By: Ryan Davey, PhD  
Last Updated: July 18, 2017
Editors: Ryan Davey, PhD and Lindsay Davey, MScPT, MSc, CDT

Could the drug Ubenimex (also known as bestatin) be used to treat lymphedema in humans? A nice study was recently published, and a clinical trial is underway. But how excited should we be?

**UPDATE: the clinical trial has now been completed, and as expected from our discussion below, the trial was unsuccessful. But the research underlying it is still both exciting and promising, and the story will not end here. Read our discussion of the results of the trial here. But for a very interesting explanation of why this is still fertile ground for new therapies, keep reading below!**

There is some buzz happening about the Ubenimex lymphedema clinical trial (see the ‘ULTRA’ clinical trial details here). Patients have inquired about the drug in our clinics, there are numerous press releases about it including one on the Stanford University website (see here), and a lymphedema blog I enjoy recently interviewed the Chief Medical Officer of the pharmaceutical company involved (see here).

I haven’t had a chance to dig into the science of this study until now. My own doctoral thesis was vaguely related (I studied natural biochemicals that direct our bodies ‘stem cells’ to do things: make new cells, turn into different types of cells, or to die), so I was looking forward to giving this study a good read.

Let me start by saying that the research supporting a possible therapeutic role for Ubenimex in lymphedema is well-done and very impressive in both its scale and depth (you can read the abstract of the study of interest here). I also sincerely hope that the clinical trial will demonstrate improvement in the lymphedema symptoms of study participants. But the skeptical scientist in me isn’t feeling overly optimistic about the likelihood that this clinical trial will show a large benefit to patients. Let me explain:

Here’s where the excitement about treating lymphedema with Ubenimex (bestatin) comes from

The Stanford University press release about this new study states:

  1. “The researchers found that the buildup of lymph fluid is actually an inflammatory response within the tissue of the skin, not merely a “plumbing” problem within the lymphatic system, as previously thought.”
  2. “…scientists discovered that a naturally occurring inflammatory substance known as leukotriene B4, or LTB4, is elevated in both animal models of lymphedema and in humans with the disease, and that at elevated levels it causes tissue inflammation and impaired lymphatic function.”
  3. “Further research in mice showed that by using pharmacological agents to target LTB4, scientists were able to induce lymphatic repair and reversal of the disease processes.”

Combined with the fact that Ubenimex (bestatin) has been used for 35 years in Japan as a chemotherapy adjuvant for leukemia (and so has a history of safety in humans), these statements make for a very enticing story and a lot of optimism.

Optimism is great, and I’m glad the pharmaceutical company is funding the clinical trial and that further research on the effects of Ubenimex on lymphedema is ongoing. But the above statements issued in the press release are not an accurate representation of the results of this key study.

What does the Ubenimex (bestatin) lymphedema study actually tell us?

The authors of this study (ref 1) used an experimental mouse model of lymphedema to investigate the effects of Ubenimex on lymphedema. Here’s what they did: they made a very small circular cut around the base of each mouse tail. This cut severs lymph vessels. As expected, the mice subsequently developed lymphedema in their tails because lymph drainage (ie, the lymphatic ‘plumbing’) was disrupted. If the mice are left untreated from this injury they will naturally recover some lymphatic function, but they will not heal completely, and will instead suffer from chronic swelling in their tails.

Here’s the exciting part: the researchers found that if you treat these injured mice with bestatin, the mice are better able to heal the damage caused to their lymphatic vessels. This in turn improves their lymphatic drainage, and permanently reduces their swelling. In other words, in mice who’ve had their tails cut, bestatin worked as a treatment for lymphedema!

(You can skip this next section if you don’t feel like reading more details about the science of the study)

The science

Through a nice collection of experiments the researchers discovered how bestatin works to reverse swelling and prevent chronic lymphedema the mice. They observed a naturally occurring substance called leukotriene B4 (LTB4) (which is a member of a group of biochemical signals known as ‘cytokines’) at the site of the injury, and noticed further that it plays a big part in the healing process. In the first three days following the tail-cutting surgery, a small amount of LTB4 can be found at the injury site. This small amount of LTB4 works to HELP the mouse heal from the injury, and when they experimentally blocked LTB4 at this stage, healing was reduced. Low levels of LTB4 appears to promote healing by encouraging beneficial immune cells to come to the site of injury, AND (importantly) by directing the damaged cells of the lymph vessels to grow and repair the damage. (If you are a cell biology fan and are curious about how exactly LTB4 is doing this, it appears to be related to activating the Notch1 and VEGFR3 signaling pathways in these cells).

Unfortunately, after the third day following the surgery, things got out of control. Levels of LTB4 got too high, which in turn caused too much inflammation.  Importantly, it also changed what cells of the lymph vessels were doing. The researchers discovered that high levels of LTB4 had the OPPOSITE effect as low levels. High levels of LTB4 told the cells to STOP trying to heal the vessels (by deactivating Notch1 and VEGFR3 activity in the cells). In other words, the mouse tails try to heal themselves for the first three days with the help of LTB4, but after day three LTB4 levels become too high, and this tells the healing process to stop prematurely. In a nutshell: low levels of the LTB4 cytokine helps lymphatic healing, but high levels prevent lymphatic healing.

So how does the experimental drug bestatin fit into this picture?  What happens if you give these mice the bestatin drug, which blocks the activity of LTB4? As you would guess, the study showed that if you give bestatin to the mice too early (before day 3), it will prevent healing and make lymphedema worse. BUT if you give it to the mice after day 3 (when inflammatory processes get out of control), it can shut down the excessively high levels of LTB4, remove the negative effects caused by high levels of LTB4, and allow the mouse to heal and recover lymphatic function!

The paper had a lot of interesting data and figures in it, but one that is particularly impactful is reproduced in Figure 1 below. In this figure you can see two mouse tails that underwent surgery. One was treated with bestatin (the bottom one), while the other was treated with a harmless solution of saline (the top one). Although it can be a little hard to see in this photo (the authors captured the photo from a video they made), in the bestatin treated mouse you can see a dye called NIR that was injected into the tail lymphatics travelling past the wound site on it’s way back into the body of the mouse (‘proximal’ means towards the center of the mouse). In the mice treated with saline no dye is visible proximal to the wound. This shows visually that meaningful lymphatic function is restored by bestatin treatment.

Ubenimex (bestatin) can treat lymphedema in mice

Figure 1: Ubenimex (bestatin) can improve lymphatic function in an experimental mouse model of lymphedema (figure adapted from ref 1). NIR dye injected into tail lymphatics is seen travelling through the wound site in mice treated with bestatin, but not in control mice treated with saline solution.

 

(If you’ve skipped the above, you can rejoin here:)

The study conclusions

Contrary to the press release, the scientists did not find that the buildup of lymph fluid is due to an ‘inflammatory response’ rather than ‘merely a plumbing problem’. Instead, they found that insufficient healing after an injury to the lymphatic system (which is a plumbing problem) is caused by an excess buildup of LTB4 (a pro-inflammatory factor) which at high doses limits normal lymphatic healing processes.

This might feel like I’m splitting hairs a bit, but I’m not. This distinction is very important, because it suggests that Ubenimex (bestatin) may help NEW lymphatic injuries heal, but ONLY if natural healing is biologically possible, and ONLY if it is given at the right time and right dose. In contrast, the press release implicitly suggests that bestatin may reduce the symptoms of lymphedema regardless of the underlying plumbing problem and divorced from the normal healing process – which is not supported by the available data. To say it more plainly: this data does not say that elevated levels of LTB4 “causes impaired lymphatic function”, it instead says that it causes impaired lymphatic healing.

But LTB4 was shown in the study to also reduce general inflammation in the area, so perhaps a reduction in inflammation could also be playing a beneficial role in curing lymphedema in mice?

Not so, or at least the data doesn’t support this hypothesis. The data suggests that the benefit of bestatin for treating lymphedema is ONLY due to its ability to stop LTB4 from telling the cells of the damaged lymphatic vessels (the plumbing) to stop trying to heal themselves, and has little or nothing to do with reducing general inflammation. This is why other anti-inflammatory drugs studied by the researchers were unable to treat lymphedema in the mice, and why the researchers concluded:

“it is unlikely that blocking inflammation alone is sufficient to reverse disease”

If Ubenimex (bestatin) has only been shown to repair lymphedema by allowing natural healing mechanisms to proceed unhindered by the inflammatory factor LTB4, should we expect it to work in human cases of secondary lymphedema?

The researchers show that LTB4 is elevated in humans with lymphedema, and that human lymphatic endothelial cells studied in a lab grow when LTB4 levels are low, but stop growing when they are high. These observations suggest that bestatin plays a similar role in humans as it does in mice.

This means that there is a good chance that if you cut a lymphatic vessel in a human and treat the human with bestatin at the right time and dose to encourage healing, that the results would be better than if bestatin were not used. That’s pretty exciting.

But how does this relate to real-world patients with lymphedema? This is where we need to start extrapolating from the data. If, as the study suggests, bestatin is ONLY beneficial because it removes a natural barrier to normal healing (which is different than “inducing repair” as stated in the press release), then we should ONLY expect it to work when healing processes are active, and when healing is possible. This is where it is important to note a distinction between the mouse experimental model and a human with the disease. The mouse model of lymphedema destroys a very small length (a few millimeters) of a handful of lymph vessels, vessels that can normally undergo some healing on their own, even without bestatin to help. The human experience of lymphedema is very different from the experimental mouse model.

The most common form of lymphedema in humans, is lymphedema secondary to cancer. This results from much greater lymphatic damage than is incurred in the mouse model. Rather than damaging a few millimeters of a few lymph vessels, in humans whole lymph nodes are removed and/or irradiated. Lymph nodes act in part as collecting chambers for lymph fluid flowing from smaller vessels toward larger ones, en route to rejoin the circulatory system at the heart. Normal injury healing processes in humans appear unable to regrow such substantial tissue structures. Worse still, as days pass after lymph node surgery and/or radiation, scar tissue can onset which further challenges lymphatic drainage and can lead to disuse of the limb (which is also detrimental). Eventually the onset of lymphedema can cause additional damage to the neighbouring lymphatic vessels in the area, through overburdening and gradual tissue changes.

Therefore, if bestatin’s only function in curing lymphedema is to remove the barrier that LTB4 creates to normal healing, then we should expect it to have little or no effect on established cases of lymphedema in humans. We can’t expect the drug to regrow missing lymph nodes, or to repair significant vessel damage. But LTB4 is present and elevated in human patients with lymphedema (as it is with inflammation caused by other injuries or conditions), so blocking it with bestatin could still have some positive effects. I’m speculating here without data, but perhaps smaller ongoing lymphatic damage caused by disease progression could be reduced or reversed by the drug. This could potentially reduce symptoms or fend off disease progression.

Could Ubenimex (bestatin) help cases of primary lymphedema where patients are born with the condition or with a predisposition to developing it?

Individuals with primary lymphedema may be less likely to respond positively to bestatin for two reasons:

  1. Primary lymphedema is caused by a lymphatic defect that patients are born with and which manifests as lymphedema either right away, or later in life, typically after a lymphatic challenge. So unlike for cases of secondary lymphedema, with primary lymphedema there is no primary injury that the body is trying to repair.
  2. Some cases of primary lymphedema are known to be caused by abnormal lymphatic cell behaviour. One underlying cause of primary lymphedema appears to be mutations that interfere with the function of a cell protein called VEGFR3 that helps lymphatic cells communicate with their environment and thus decide what to do (ref 2). Unfortunately, the current study suggests that LTB4’s action on lymphatic cells is via VEGFR3. If this is true, then blocking LTB4 with bestatin in these patients could have no impact whatsoever on their lymphatic cells – because the cells simply can’t respond to it. The same would be true for cases of primary lymphedema caused by some other defect in a piece of the cell machinery that works in concert with VEGFR3.

However, cases of primary lymphedema not caused by disrupted VEGFR3 might benefit from bestatin in the same way that secondary lymphedema might: by helping reduce and reverse smaller ongoing lymphatic damage associated with disease progression. But once again, we are hypothesizing without data.

Summary

Ubenimex (bestatin) can reverse the development of experimental lymphedema in mice by blocking an inflammatory protein called LTB4 that prematurely stops the normal healing process. Blocking LTB4 at the right time allows the mice to heal their lymphatic injury and avoid getting chronic lymphedema.

This discovery is an exciting and significant contribution to our understanding of lymphedema, and offers a novel and potentially beneficial treatment avenue for the disease. But the available data suggests that Ubenimex will unfortunately not represent a cure for lymphedema in humans.

A cure for lymphedema in humans will require repair or regeneration of the significant underlying lymphatic ‘plumbing problem’ found in humans, a problem that natural healing processes are seemingly unable to repair. Even though Ubenimex isn’t expected to solve this underlying problem, it could potentially help with the symptoms of the disease by encouraging normal lymphatic repair processes to heal the smaller ongoing lymphatic damage that occurs with disease progression. There is currently no data for us to look at, so we don’t know if Ubenimex will offer a significant benefit to patients, a minimal benefit, or no benefit at all. But since Ubenimex has previously been shown to be relatively safe and well tolerated, it’s both exciting and heartening that a pharmaceutical company is funding a clinical trial to find out.

References

  1. Tian W., Rockson S.G., Jiang X., Kim J., et al. Leukotriene B4 antagonism ameliorates experimental lymphedema. Sci Transl Med. 2017 May 10;9(389).
  2. Karkkainen M.J., Ferrell R.E., Lawrence E.C., Kimak M.A., et al. Missense mutations interfere with VEGFR-3 signalling in primary lymphedema. Nat Genet. 2000 Jun;25(2):153-9.

22 Comments

  1. deb deb says:

     One of the problems lymphedema biomedical researchers have to deal with is establishing an animal model of “chronic lymphedema”. There is no “chronic disease” animal model for lymphedema, to the best of my knowledge. I have not read the entire research article yet, but I generally concur with the opinions expressed in this article from what I have heard, and I know that this finding of changing levels of the targeted molecule was discussed at a recent forum of scientists in Chicago. However, it is surmised that chronic lymphedema does create some degree of a chronic inflammatory state. There is still so much to be discovered in lymphedema research, and we do all need to get behind the biomedical research to support its movement forward towards better understanding of the disease! It is drastically behind compared to other chronic diseases because of poor funding, and it is only biomedical research that will lead to enough of an understanding of the disease to create new treatments for it.

  2. Ryan Davey Ryan Davey says:

    I think you hit the nail on the head Deb. Part of the misunderstanding that this article has generated in the online discussion comes from the fact that physiological processes at play during induced acute lymphatic injury (such as in the mouse model) are different from those active during chronic lymphatic insufficiency – so drugs that are found to be beneficial in the mouse model may have relevance to lymphatic HEALING processes that occur BEFORE the onset of lymphedema, but be less relevant (or irrelevant) to the chronic disease state. So the mouse model is certainly not an ideal model for human lymphedema, but given that lymphedema is a progressively worsening condition (if not managed) typified by ONGOING lymphatic damage, chronic inflammation, and tissues changes (such as hardening), there is a chance that factors involved in early lymphatic healing of the primary injury may also be beneficial for addressing ongoing damage and repair processes during chronic disease. So we should remain hopeful that pharmaceutical options will become available to help manage symptoms and/or hopefully delay/prevent disease progression. And it is very nice to see a pharmaceutical company getting behind a clinical trail for secondary lymphedema – getting commercial interests involved is a necessary step :)

  3. Alla Alla says:

    Yes. Certainly, every drug works better, if it is being used as soon as possible, at the beginning of the inflammatory process. But, in reality, acute lymphedema ( acute lymphatic injury) doesn t exist. Because it turns immediately cronic. It the LE stars, it is irreversible, even so it is very small. Besides, only the patients , whose diagnose of LE wes confirmed by the lymphoscintilographie were able to participate at the first phase of trials (with humans). But this exam only shows LE in serious cases, and that means that all the patients have serious lyphatic injuries. Eves so, the results of the trials are good.

  4. Ryan Davey Ryan Davey says:

    Thanks for your comments Alla :)

    Yes, human clinical trials are usually very well controlled. Only ‘typical’ patients with well-defined and well-established disease are usually included. Unfortunately this can sometimes mean that test results don’t accurately reflect what might observed in a more varied population that includes early, atypical, or less well-established cases.

    The process of developing lymphedema after a lymphatic injury (or congenital defect) can be very fast, or it can be slow. In fact, it’s likely that many patients first show lymphedema symptoms only after some event happens that overburdens their newly fragile lymphatic system, thus starting the cycle of swelling. During the phase where lymphedema is present but not yet showing, inflammation is also present and is likely contributing to symptom onset. Even after lymphedema becomes established, progressive worsening can still occur over time (and usually does without management), and again, inflammation likely plays a role. It’s possible that this drug candidate might be particularly beneficial at these stages – to delay progression or lessen symptoms. But you’re right, in the end this drug will not be able to reverse lymphedema.

  5. Anonymous Anonymous says:

    I remember talking to Stanley Rockson many years ago, when he was testing the cox-2 inhibitor (the one that was pulled off shelves) on actual patients with lymphedema. At the time, he thought he was just months away from publishing, LOL. And I remember him saying that the drug appeared not just to control symptoms of LE, but also to repair damaged tissue. I kept waiting for him to publish that, but never saw anything. I know side effects on kidneys etc. were an issue so maybe that had something to do with it? Now, he’s got another drug and the basis for your objection is the way it was tested on mice. I’m sure you’re right these are valid objections. i’m just hoping because he’s already tested a similar drug on humans and found it works that helps to address the objections you raise. Fingers crossed– thanks!

  6. Ryan Davey Ryan Davey says:

    My fingers are crossed as well. This current research comes directly out of the earlier promising Cox-2 inhibitor work that you mention – so the story didn’t end, it’s just been evolving. The drug they were investigating was Ketoprofen. In this current study they show that the efficacy of Ketoprofen is likely attributed entirely to its ability to inhibit LTB4. Ubenimex (bestatin) is a more direct way to accomplish this, with a well known drug, and potentially with less side effects – hence the excitement about Ubenimex. So the story continues!

  7. Anonymous Anonymous says:

    Anonymous said: “At the time, he thought he was just months away from publishing, LOL.”

    I find your comment to be extremely distasteful. For those of us sitting on the sidelines dealing with this condition every day, this is not a laughing matter. At least Dr. Rockson is out there trying to solve this horrible condition. Many solutions are found through trial and error (or even by mistake). Sure, maybe we all get overconfident in what we are passionately pursuing but you should be well reminded to think of the people suffering everyday and should choose your words and comments more wisely and with some heart.

  8. Deb Deb says:

    I view all of this as critically important work.  The bottom line is that something will be more clearly revealed because there is molecular research activity directed towards it.  It is not sustainable to think that every lymphedema patient can afford and physically manage their chronic condition into old age….and there are so many undiagnosed cases and suffering patients who can’t afford physical treatment as well because of poor attention to this difficult disease.  It is important to tease all of this apart and understand it for what it is, and also realize the absolute importance of this research, compared to countless redundant research studies done that compare this type of physical management to another type, all of which is constantly costing the patient money out their own pockets…we need good biomedical research to help this “orphaned” patient group to hopefully increase understanding and make the management of this disease more efficient, thus helping a person “manage” the progression of the disease into a person’s older years.  A safe medication could potentially do that, in the absence of a cure.  

  9. Ryan Davey Ryan Davey says:

    Well said, thanks Deb.

  10. Ryan Davey Ryan Davey says:

    I hope the person who left the “LOL” comment wasn’t trying to make fun of Dr Rockson’s efforts, and at least I hadn’t interpreted their comment that way. But you are definitely correct that sometimes we can get carried away talking about lymphedema from a clinical or scientific perspective, without being careful to consider that there are a lot of frustrated people “sitting on the sidelines” who are waiting for help, and listening to the conversation. Thank you for contributing to the conversation, and for your helpful reminder.

  11. Deb Deb says:

    I am compelled to respond to Ryan’s recent comment and other’s recent comments, as I was at a conference recently where there were MDs expressing their skepticism in a somewhat sarcastic way in front of an audience of therapists and patients alike, at Stanley Rockson’s recent clinical trials, and his statement that he was “close” in 2011 and now in 2017.  I was very deeply concerned about what I was witnessing at that moment.  I do hope that the longstanding traditional care providers within the lymphedema treatment sector are not “threatened” by this upswing of molecular research into this disease and the possible new treatment modalities it might bring….that would be very sad indeed.  We all must work together to promote the realization that historically, biomedical/molecular research into chronic diseases has only enhanced the understanding and development of some of the best treatment practices for those diseases, and in turn also has increased the awareness and recognition of the chronic disease in the eyes of medical community and also in the health care funding and provision sector overall!  In Canada, this would be a huge benefit to our lymphedema community within the “universal care for all” philosophy that most lymphedema patients do not get recognition under (!), unless they are extremely sick with cellulitis or other serious complication of their LE.  For example, I do believe we all need to begin to articulate that LE has a large chronic inflammatory component to it, based on many research findings of many researchers whose work has evolved up to this point, because chronic inflammation is at the root of many diseases that receive provincial compensation for treatment to control disease progression. So we must all realize where we are at in this time in the evolution of LE scientific exploration, and not be threatened by the rise in biomedical research into this condition, but rather, welcome it and follow it closely for all the benefits it can potentially offer this particular disease.  So thank you Ryan for this blog and comment forum and for your consistent and timely comments in addressing all the newest developments in research as well as other interesting items you bring to your blog!  

  12. Ryan Davey Ryan Davey says:

    Thanks for your comments Deb. Your idea about emphasizing lymphedema as a disease of inflammation in order to drum up healthcare funding for it is interesting.

    I’m not sure of the source of the overly zealous skepticism (to the point of sarcasm) that you witnessed surrounding Dr Rockson and his group’s work. The quality of their research is certainly impressive and not easily dismissed, and the fact that it has spawned a clinical trial is fantastic. One possibility for overly zealous skepticism may be just what you said: that it threatens established care practices and those who deliver it. This is valid. An alternative (or additional) possibility is that the skepticism is in response to how the Ubenimex story has been told. When the story was spun for public consumption I think perhaps it came out a bit too flashy and overly optimistic. This is often the case with new research, and it’s a difficult balance to strike, especially when the research and it’s conclusions are textured and nuanced. So I wonder if the overly enthusiastic skepticism that you observed was a response to an overly enthusiastic public dissemination of the work? Because when we’re talking about chronic conditions, real people actually read what is being written, and they want to discuss it with their healthcare providers. In fact, my own interest in writing about Ubenimex was aroused by what I felt was potentially misleading online information about it. But I have the fortune of being a slow and plodding writer so I had ample opportunity to dampen my own sarcastic temperament :) I wonder if on the spot, and in person, I too would have come across sarcastically dismissive of their work? I hope not. It’s certainly well done and promising.

    Thanks for the interesting discussion!

  13. Robert J Robert J says:

    As someone who suffers from both lymphedema and pulmonary hypertension I found it interesting that bestatin was hopefully a cure for both problems.

    Have you heard of any further developments on bestatin used to treat pulmonary hypertension?

  14. Ryan Davey Ryan Davey says:

    I’m sorry, I don’t know anything more about using bestatin for pulmonary hypertension, but that’s interesting.

  15. Laura Duncan Laura Duncan says:

    I am a primary lymphie (over 45 years). I started taking Ketoprofen, on my own, with primary doctor’s blessing. The effect was phenomenally miraculous. My skin had developed an “orange peel” consistency and was very rigid and hard. After just one week on Ketoprofen(yes ONE!), my skin returned to normal – soft and smooth. I take 1 pill a day to maintain the effect.

    So anything, any pill, that Stanley Rockson says will help my lymphedema, I will gladly consume. He’s just a little shy of rock star legend in my book. Thanks for the article. It is very insightful.

  16. L.D. L.D. says:

    For Robert J —- They discontinued the trial for the pulmonary part. They stopped after the Phase 1 trial proved disappointing(?). But they have started Phase 2 of the lymphedema trial, so I guess that Phase 1 was satisfactory.

  17. Ryan Davey Ryan Davey says:

    Your positive personal experience with Ketoprofen is interesting. For patients like you that appear to respond positively to LTB4 inhibition it stands to reason that Ubenimex may be equally as effective (or perhaps more effective) and potentially with less risk of side effects. I’m glad you’re on a better path with your self-management. Thanks for sharing :)

  18. Ryan Davey Ryan Davey says:

    Thanks Laura

  19. Riley Riley says:

    Does anyone know when the human trial is due to be completed? I’d love to try Ubenimex and see how it works for me?

  20. E. D. E. D. says:

    For L.D.

    I would greatly appreciate it if you could tell me the strength of the Ketoprofen that you are taking.  I know there’s a 50mg capsule, but I read that there is a time release version, as well.  Are you taking either one of those, or something else?  Thanks so much.

  21. Stella Stella says:

    I am surprised that no one has cited the possibility that bestatin could be given to the cancer patient while undergoing radiation treatments to prevent lymphedema by the suppression of LTB4 to allow for lymphatic repair when the damage occurs. Since Bestatin has been used by the Japanese as a cancer drug for decades, it would be interesting to ascertain if patients taking bestatin developed lymphedema after node biopsy or removal or radiation. If that data supports bestatin as preventative, millions of people undergoing cancer treatment will not have to live with lymphedema after surviving cancer.

  22. I like this idea very much as well Stella. Wouldn’t it be fantastic to have a cancer drug that might also reduce your risk of lymphedema by encouraging the healing of lymphatic damage? Unfortunately I can’t comment on the viability of this idea. I know very little about how Bestatin is used in Japan (indications, dosage, timing) so I can’t comment about it’s potential utility for cancer patients who are at risk of lymphedema (such as breast cancer patients), nor do I know if typical drug dosage and timing would overlap with the sweet spot for lymphatic healing… An easier first strategy for follow-on clinical trials would be to evaluate whether or not Bestatin at optimal concentrations and timing could help reduce the onset of lymphedema, and if it can, there would be a stronger argument for introducing it as a dual-effect drug. Thanks for the comment :)

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