Today’s post is about a drug originally proposed by Wayne State University in the US, but so far approved and widely used mostly in Asia. China is the big producer/user and Italy is the outlier where it is also used.
Therapeutic Developed in United States Benefits Many in Asia
Since Wayne State University gastroenterologist Milton Mutchnick, M.D., first proposed using the hormone-like peptide thymosin alpha 1 to combat Hepatitis B in the mid-1980s, the drug has seen both outstanding success and somber letdown. Overseas, thymosin has become an important tool for fighting Hepatitis B, cancers and infections. Within the United States, its promise remains in doubt decades later.
Today we consider
repurposing a naturally occurring peptide from the thymus to restore
balance/homeostasis to the immune system in people with autism.
It has been
well documented in the research (for example by Paul Ashwood at the MIND
Institute) that the immune system can be dysfunctional in many people with
autism, but in different ways.
Some people
with autism suffer from flare-ups when their symptoms get much worse. These flare-ups can be immune mediated,
meaning that the rather complicated pro-inflammatory / anti-inflammatory
balance has been disrupted. A reset is
needed.
In some
cases, a short course of oral steroids is enough to provide the reset, but
often it does not work.
One reader
of this blog was proposed by his Italian doctor to try Thymosin alpha 1 shots to treat
his son’s autism flare up. Not
surprisingly, living in the UK, he had never heard of Thymosin alpha.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747025/figure/F2/
What
is Thymosin alpha 1?
The following paper
provide an excellent explanation:
Thymosin alpha 1: A comprehensive review of the literature
Thymosin alpha 1 is a peptide naturally occurring
in the thymus that has long been recognized for modifying, enhancing, and
restoring immune function. Thymosin alpha 1 has been utilized in the treatment
of immunocompromised states and malignancies, as an enhancer of vaccine
response, and as a means of curbing morbidity and mortality in sepsis and
numerous infections.
Thymosin alpha 1 has long been recognized as an
immune enhancing, immune modulating, as well as an immune restoring agent, and
as such it has been utilized in several clinical and research settings. The
synthetic form of thymosin alpha 1, thymalfasin, is approved in more than 35
countries for the treatment of hepatitis B and C and as an immune enhancer in
several other diseases
Thymosin alpha 1
functions as a toll-like receptor (TLR)-9 and TLR-2 agonist in both myeloid and
dendritic cells, the professional antigen-presenting cells. By targeting TLRs,
thymosin alpha 1 can stimulate the adaptive immune response, which is essential
for fighting viral, bacterial, and fungal infections and cancers, as well as
stimulation of posterior humoral immunity. Additionally, thymosin alpha 1 can
increase levels of IL-2, IL-10, IL-12, interferon (IFN)-α, and IFN-γ. The role
of thymosin alpha 1 in stimulating T-cell dependent antibody production is also
the reason why it has been considered as a vaccine adjuvant for enhancing
response to vaccines.
Thymosin alpha 1 has a wide range of biological
activities that range from anti-tumor to immune-modulating properties. The
immune response of thymosin alpha 1 is due to its action in elevating the
activity of T cell maturation into CD4+/CD8+ T cells. It works to directly
activate natural killer cells as well as CD8+ T cells through which it kills
virally infected cells. Thymosin alpha 1 has a negative effect on IL-1β and
tumor necrosis factor-α, which in turn leads to a decreased inflammatory
response and is quite beneficial in conditions such as chronic hepatitis and
acute pancreatitis.
Thymosin alpha 1 has exhibited
the ability to restrain tumor growth, hence its use in the treatment of various
cancers. It has anti-proliferative properties which have been exhibited in lung
and liver tumor metastases.
Since thymosin alpha 1 is a
polypeptide naturally present in the thymus, it plays a fundamental role in the
control of inflammation, immunity, and tolerance. Thymosin alpha 1 has an
immune-modulating action through its interaction with toll-like receptors. Due
to the action of thymosin alpha 1 on other cell types, it is used as a
therapeutic agent for diseases with evident immune dysfunction. Clinical trials
with thymosin alpha 1 for diseases like DiGeorge syndrome, non-small cell lung
cancer, hepatocellular carcinoma, hepatitis B and C, HIV, and melanoma have
been conducted and yielded promising results. FDA approved the orphan drug
thymalfasin (Zadaxin) for treatment of malignant melanoma, chronic active
hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma
due to its immunomodulatory and anti-tumor effect.
Thymosin
alpha 1 for auto-immune autism flare-ups?
Thymosin alpha 1 is no
wonder drug for autism, but it looks like it has a place in the autism toolbox,
for when symptoms take a sharp turn for the worse and you need a reset back to
your baseline autism.
If it solves the flare-up, great. If not, you just move on to the next option.
Conclusion
Italy does seem to have a different view of medicine. They are big on the medical use of probiotic
bacteria. They have treatments for GI problems that seem to be unheard of in
other countries. It is home to the novel idea, that I found appealing, to use
nerve growth factor (NGF) eyedrops to prevent dementia.
Italy is also home to the use of Thymosin alpha 1 shots, to reset
the immune system after an immune-related autism flare-up. I think it is a great idea and I doubt it is
expensive.
Most readers of this blog
are in North America, where Thymosin alpha 1 is not an approved drug. In China,
India, Italy and another 30 countries it is widely available.
As Zadaxin, Thymosin alpha 1, is produced by SciClone Pharmaceuticals in China. They provide the following summary:
http://www.shijiebiaopin.net/upload/product/2011121219115812.PDF
It looks like our readers who have an autism doctor in Italy have some interesting options.
Wayne State University never sought patent protection for Thymosin alpha 1 in
China, which they now regret.
Hi Peter what do yuo think about LDN theraphy?It can have the same effect of TA-1?
ReplyDeleteLow dose naltrexone (LDN) is a safe and inexpensive long term therapy that does benefit some people with autism. It is one of very many anti-inflammatory therapies that work in some types of autism. Some people take curcumin, some PEA, some VSL#3 etc. The effects are all different, in some people there is a benefit, but for others there is none.
DeleteYou could use thymosin alpha shots long term, but it looks like they may be beneficial as a short term therapy, like oral steroids, for autism flare-ups.
Been recommended it too, never tried it. our combo of ivig, mirokrom, galavit, azithro, diflucan and malarone, while pretty heavy, works wonders. Not just on the pans but also the autism. she is the best she has ever been and if by some magic she became fully verbal today, I don’t thnk there would be much left.
ReplyDeleteTatjana, I assume Mirokrom is Russian cromolyn sodium, the mast cell stabilizer?
DeleteGalavit (Sodium aminodihydrophthalazinedione) is an old Russian drug that seems to have wide-ranging effects.
Hi, malarone has been tried on my son for 10 days, it had no effect, but a little calmer, cromoline sodium had an effect from the first administrations, calmer and happier and less histamine on the face, cromoline sodium Food allergy sufferers should not be missing, but the price is quite expensive, a dose of azitrox 250 mg keeps histamine away for a week for my son, I think it stops the inflammation ... since I'm treating my son, I came to a conclusion that there is a problem in the digestive tract (intestine) and I think it is viral ....
ReplyDeleteIf that worked, I would try galavit too. Yes, cromolyn sodium. Our russian immunologist wanted it paired with Ketotifen but it had the rare but known in children side effect of making her agitated. We have loved veru much the effect of both. Brillia also worth a try.
ReplyDeleteI gave my first shot of Thymosin alpha 5 days ago. Did not see any reductions in coughing, phlegm or improved behaviours.
ReplyDeleteHow can i diagnose autism flare ups related to intestinal issues e.g. burping, pain, phlegm, being sick ect
My autism doctor is unwilling to give propranolol for anxiety, he wants to give rivotril, which i am unwilling
I already treated h pylori with antibiotics
I tried rifaxamin, cromolyn sodium, but did not help
Prucalapride does not help much for constipation
If i stop oxy powder, constipation gets worse.
Started using digestive enzymes
Did a colonic and a lot of yeast was coming out
I would recommend seeing the Italian gastroenterologist that I mentioned before, Dr Federico Balzola. Then you you may get a definitive answer. He is probably worth the long waiting time.
DeleteFor example, coughing can be a sign of reflux as can be white coloured phlegm. Other colours of phlegm are linked to other conditions.
https://www.healthline.com/health/green-phlegm
Asgar - aggressiveness/self injury can also be a sign to gut problems. In fact, it can often be the only obvious sign. Keep working on the gut, figuring out food allergies and sensitivities, trying things like butyrate etc. Just keep going. It pays off in the long run.
DeletePeter,
ReplyDeleteAbout 3 weeks ago, my son Vik had a sharp increase in the throat clearing vocal tic (sounds like the peppa pig grunt). This was the same tic that he had last summer which slowly faded away. This time it came back overnight with a much higher frequency (>1000 times a day). Along with it, there was clear increase in irritability, anger, rigidity and general non-compliance. Having read about PANS, I took him to an allergist/immunologist who also had experience with PANDAS. He ordered blood work to test for allergies and prescribed Nasacort Nasal spray 55mg (a glucocorticoid). We are on day 5 of this spray + a couple of days of children’s claritin at night. The frequency of his tics have roughly halved and we see that he is much more relaxed and has more speech. Interestingly, his serum IgE values came out to be very high (728 IU/ml), almost thrice the normal max limit. He also had elevated IgE values for ragweed and timothy grass. His Igg values were normal and he did not seem to have a previous strep infection.
Vik is 4y 8mo old now and about 4-5 months ago, barring the lack of conversation and his social anxiety, he was a happy and compliant boy for the most part. Today he feels like a different person, hard to manage, very hyperactive, makes odd facial expressions and tics and has episodes of rage. I have noticed some similarities with tpes’ child and was wondering if I should pursue more aggressive treatments like IVIG etc.
(Full case history on the ‘polypill-for-autism’ page)
Regards,
Anvesh
Anvesh, IVIG is a very interesting potential therapy, but it can become very expensive, if you need to keep repeating the infusions.
DeleteThe article below and the paper it links to will be of interest.
Autoimmune targets in Cunningham Panel™ predict IVIG treatment response in subset of autism patients
https://www.moleculeralabs.com/cunningham-panel-predict-treatment-response-autism-patients/
The Cunningham Panel itself costs $925. IVIG costs vary depending on where you live. As usual, the US is the most expensive; some people, or their insurance company, pay tens of thousands of dollars. Some parents find it works well, but they cannot afford to keep paying for it.
It is well worth trying an oral steroid like prednisone, which is ultra cheap. It may be good enough.
Anvesh, I have a child with Pans. I would invest in a very thorough immunological asessment. We use a Russian doctor, Kiril Shlyapnikov, you can go to his clinic or online consults. We also use IVIG, since a positive Cunningham panel gave us monthly doses paid for by the state. Its essential that you deal with this - Pans is much worse than autism as yoi can probably see yourself. You can find me via my name on fb, Tatjana Pes, if you want to talk more.
DeletePeter,
DeleteThanks for the reply. When I asked our allergist/immunologist for an alternative to the nasal spray, he did mention that the only alternative is prednisone, which he said he does not want to try (I have not asked him to elaborate). My son is starting to do better, so I might continue with the current prescription for some more time. However, I am convinced that I should get the Cunningham panel done. I had once read a spectrum news article which was ambiguous about the results from the Cunningham panel, but now I think the potential benefit is worth the cost. About IVIG, we live in the US, but we are originally from India, where I gather the cost of IVIG is relatively affordable out of pocket. I will need to double check on the quality though. I do wonder if beyond PANS, IVIG might be an effective therapy for autism itself? The paper mentioned shows some effect but they are not dramatic and there seems to be some side effects which might need constant monitoring. But I do think it might be worth a try.
Tatjana, thank you so nuch for your comment. I have sent you a request on fb. I would love to talk to you more about the tests and your experience with IVIG.
Regards,
Anvesh
Anvesh, my son uses Fluticasone another common steroid nasal spray. The intranasal delivery is to reduce how much gets into your blood. To treat autoimmune encephalopathies you need the steroid to reach the brain. Steroids are small molecules and are lipophilic so they usually can cross the blood brain barrier. So the nasal steroid with not have same effect as the oral steroid. The oral steroid will go all over your body and hence may cause side effects if not used with care.
DeletePosting an update here. We got the result from Cunningham panel for my son, Vik. Three of the antibodies were termed 'borderline' and CAM Kinase II was elevated.
DeleteHere is the link to the report: https://imgur.com/a/QSplKXl
Anvesh
I tried Fluticasone nasal spray and Prednisone for Pans symptoms for my son, but did not help. A short course of Amoxicillin did help. Cunningham panel test did show elevated Cam kinase II. I am looking into Enzyme potentiated desensitisation (EPD) and Low dose naltrexone.
ReplyDeleteThymosin is an mtor inhibitor.
ReplyDeletehttps://pubmed.ncbi.nlm.nih.gov/26002438/
Stephen
Hi Peter, I came across a peptide called KPV (Lysine, Proline and Valine) - as a mast cell stabilizer - the FB groups also seem positive with no side effects (for a short usage). Wondering if you have come across this and its safety profile.
ReplyDeleteThis question came up previously. KPV peptide does have anti-inflammatory properties and is researched for IBD. It is not very stable and breaks down in the gut. It is unlikely to reach the brain and it is thought unable to cross the blood brain barrier.
DeleteIn someone with GI problems plus autism it might well have a benefit. It is seen as safe. It looks pretty harmless to trial it.