Neurofibromatosis type 1 (NF1)

Dear Friends,

A few days ago I was responding to a kind request to help with some ideas for a young girl dealing with a benign but fast growing neurofibromatosis type 1 (NF1). There are some tumors of about 1 cm located in difficult areas making it impossible to removed them surgically, and are life-threatening.  Below is my response to that request. I thought is good to share it here, as we never addressed this subject “” and it may help other people too. If you have comments, remarks, regarding the content below or other ideas for treatments relevant to neurofibromatosis type 1 (NF1) patients please write a comment below. 


Selumetinib seems to be an option that has been granted in 2019 breakthrough designation by FDA, based on the following results blocking MAPK/ERK pathway.

Update April 2020: the patient is on Selumetinib and she is doing very well.

Assuming this is not a glucose avid tumor, but its growing fast, the tumor must use respiration in order to produce the required energy. On this line:

–          Glutamine and fatty acids will be in this case critical nutrients for driving cancer cell proliferation. Indeed, it has been showed that NF1 associated tumors can be targeted via glutamine depletion and glutaminase inhibition (Ref.). Deplition of Glutamine can be done with Phenyl Butyrate, and FDA approved drug. Avoiding foods (like red meat) containing large amounts of glutamine may also help. I just checked and see if this idea has been applied before and it seems where was some phase 1 clinical trial on Phenyl Butyrate in children with NF1-related plexiform neurofibromas but there was no follow up, probably due to the financial limitations. EGCG and Curcumin supplements may help here too.

–          Another way to make use of the fact that the tumors may use mainly oxidation is to use mitohocondria inhibitors such as Metformin, or other mito inhibitors that I listed here

–          Given that these tumors rely on mitochondrial energy production, another approach could be to consider inducing catastrophic oxidative stress combining e.g. mTOR inhibitors (such as Metformin – indirectmTOR inhibitor) with HDAC inhibitors (such as Valproic Acid) with thioredoxin reductase inhibitors (such as Auranofin). Here is a paper from Harvard discussing this approach Here is another reference discussing a similar approach in (malignant) NF1

–          Also because the tumors rely on mitochondrial energy production, access to oxygen is very important for their growth. This is why they should be sensitive to angiogenesis inhibitors. Thalidomide is an angiogenesis inhibitor Celecoxib is another one that targets angiogenesis. Mebendazole could also be useful here. Here is a longer list of angiogenesis inhibitors

Furthermore, it is known that Ras, angiogenesis, COX-2 could be good targets in NF1. The development of NF1-associated tumors is largely explained by the underlying defect of the NF1 gene which results in activation of the RAS proto-oncogene- a key mechanism of tumorigenesis.

–          Drugs to target Ras:

Mevalonate is also an essential precursor for producing isoprenoids such as farnesylpyrophosphate and geranylgeranylpyrophosphate. These isoprenoids are especially important for anchoring small GTPases to the membrane before they function; e.g., Ras GTPases modulate proliferation and apoptosis, Rho GTPases control cytoskeleton formation, and Rab GTPases are essential for intracellular vesicle trafficking. Inactivation of these small GTPases alters cellular functions. (Ref.) inhibiting Mevalonate pathway:

    • Statin (Atorvastatin or Pitavastatin) to inhibit mevalonate
    • Dipyridamole to maintain effectiveness of statins
    • Vitamin E to maintain effectiveness of statins
    • HCA supplement may also help here to reduce input on mevalonate pathway
    • Bisphosponates (e.g. zoledronic acid) will also inhibit mevalonate pathway and as a result Ras (Ref.)

Geranylgeraniol addition via food could be fine since the goal here is to inhibit Ras and not Rho. This could reduce the chance of side effects from Statins. Flaxseed oil contains good amounts of Geranylgeraniol.

Note: Such approach to target mevalonate has been proposed in the past although a little different   Indeed, pilot studies concerning the use of drugs—such as the protein farnesyltransferase inhibitor tipifarnib are underway

–          Drugs to target COX2

    • Celecoxib

Other targets in neurofibromatosis type 1 (NF1) is neurofibroma, are Schwann cells, fibroblasts, mast cells, neuritis, and collagen.

–          To target Mast Cells

–          To target fibroblasts

    • Tranilast (also addressing mast cells) or NSAIDs. Indeed, here are publication indicating Transilast may help: Tranilast, an anti-allergic drug, down-regulates the growth of cultured neurofibroma cells derived from neurofibromatosis type 1 Tranilast inhibits the expression of genes related to epithelial-mesenchymal transition and angiogenesis in neurofibromin-deficient cells

Natural treatments:

  1. CAPE that can be found in high amounts in the Propolis from Manuka has also be found to stop the growth of NF1 tumors:
  1. Strong antioxidants such as NAC (supplements found online) may help NF1 patients (although may not help the direct fight against the tumors):

Other references:

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

Schwannomas cells cand be targeted by Artesunate

Dietary intervention rescues myopathy associated with neurofibromatosis type 1.

Absence of Neurofibromin Induces an Oncogenic Metabolic Switch via Mitochondrial ERK-Mediated Phosphorylation of the Chaperone TRAP1.

In conclusion, there are several drugs and supplements that are easily accessible and could be add value in the treatment strategy against NF1. Using the above information, I would create a cocktail of drugs and supplements to increase the chance of success.


This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here:

Related Articles

13 thoughts on “Neurofibromatosis type 1 (NF1)

  1. Daniel you are a great person because of your altruistic help to so many people.
    I am proud to have met you and your wonderful blog.
    Hopefully we can help everyone to bring research advances to people who have no more therapeutic options.
    I have many ideas to help but my lack of time is my biggest obstacle.

    Kind regards

    1. Thanks Manuel! I think this is what we have in common many of us active here and trying to help others, family, friends. Time is so limited and goes so fast indeed. When you have ideas, just share them here – one line it’s enough and maybe some of us will be triggered and go deeper on that line.

      Kind regards,

  2. I am completely sure that we have real therapeutic options of great potential. I don’t want to trust too much but I think so.
    From my humble opinion it would be good and it would help new readers to structure the treatments.
    I believe that the metabolic approach is adjusted to all types of tumors to a greater or lesser extent and a “route example” therapy could be done.
    All this with the subsequent disclaimer logically.
    There is very valuable information in all the blog and forum discussions but it is difficult to read all of them.
    On the other hand I understand that it is a lot of work for you. For my part I will try to compile my treatment and the most relevant comments in my post of “gliosarcoma”.

    Kind regards

    1. Thanks Manuel. I agree. There is a lot of content on this website and it may be too much for most new to the field. I am considering to simplify things in the future, indeed.

      Kind regards,

  3. Hi Daniel,

    Can you help to find a good Vitamin e supplement? I´d like to add to my chloresterol approach and maybe could be to my damaged inmmune system .

    Very informative post this one, we always could learn something 🙂

    Thank you

  4. Good night Daniel,

    I have reading some info in differents websites and i´m not sure if in cancer is more beneficial to take a product focused on Tocotrienols more than another forms. So in your opinion, would you take separately these two forms (Morning – night) and .

    Or could be a better approach two caps daily of the second one ? )only tocotrienols 🙂

    thank you daniel!

Leave a Reply