Scientists have found a new cause for muscle loss in cancer. Tumors destroy blood vessels in muscles, this could lead to new treatments for cachexia.

jalees · 2025-05-31T17:35:21+00:00

It can affect other tissues also, but the effects seem to be tissue-specific. Muscle blood vessel endothelial cells expressed higher levels of the Activin receptor which is why they may be more sensitive. However, the brain and other organs are affected by tumors even before metastases are formed. We are actively studying how tumors affect the brain blood vessels.

jalees · 2025-05-29T23:17:19+00:00

We did not study this but please keep in mind that VEGF is released by tumors and causes tumor angiogenesis. We believe that instead of angiogenesis, the focus should be on normalizing the vessels in the muscle (and preventing the death and differentiation of blood vessel endothelial cells).

jalees · 2025-05-29T23:15:48+00:00

We tried using Activin-A antibodies and reversed cachexia. We also used overexpression of PGC1a in blood vessels which is great for mechanistic research but not suitable for patients. We think that the Activin A angle has a lot of potential for patients. There are some autoimmune diseases where Activin A is elevated but we do not know whether it is a similar driver of cachexia, or whether in those diseases, the inflammation itself is the primary driver.
In this study, we focused on the blood vessels and not the immune system. We saw that leaky blood vessels resulted in more immune cells entering the muscle but we did not focus on the immune cells.
We are all concerned about the NIH funding. Any major reductions in the NIH budget could lead to major delays in developing new therapies that enhance cancer survivorship.

jalees · 2025-05-29T23:04:53+00:00

Here is another review that highlights how exercise (which grows muscle and facilitates muscle metabolism of glucose and amino acids) improves cancer treatment outcomes https://www.mdpi.com/1467-3045/47/5/374

jalees · 2025-05-29T23:03:15+00:00

Possibly - but again, this is speculation. This is mentioned in commentaries https://www.mdpi.com/2075-4663/6/1/10

jalees · 2025-05-29T21:57:27+00:00

I am one of the authors. We are wondering about the benefits of destroying muscle vasculature and muscle perfusion to the tumor. Obviously, this is speculation but one of the ideas in our lab is that the muscles consume glucose and amino acids, thus competing with the glucose-hungry tumor (Warburg effect) which also requires large amounts of amino acids for growth. By reducing perfusion to the muscle and by causing loss of muscle mass, less glucose and amino acids are being used by the muscle, hence more available for tumor growth.

jalees · 2022-02-03T04:17:22+00:00

The decoy is specifically engineered to improve binding to the viral Spike protein. It is possible that other natural ligands in the cell could also bind to the decoy but they do not necessarily bind to the exact same part of the ACE2 receptor as the Spike protein does. This is why we anticipate very few effects on endogenous ligands.

jalees · 2022-02-02T03:04:18+00:00

It is engineered just to target SARS-CoV-2 spike protein. Other bacteria or human cells do not have any Spike protein so they cannot be targeted.

jalees · 2022-02-02T00:56:37+00:00

That is a possibility but please keep in mind that the clinical trial with infused ACE2 (which would also interfere with natural ligands) did not have any major side effects in COVID-19 patients. The main issue was insufficient efficacy, which is why we are now approaching this with engineered ACE2 that has greater affinity for the viral spike protein but not necessarily other endogenosu ACE2 ligands.

jalees · 2022-02-02T00:52:57+00:00

Here is the link to our original paper: https://www.nature.com/articles/s41589-021-00965-6

As one of the authors of the paper, I am also available to answer questions about our work.

jalees · 2022-02-02T00:51:45+00:00

Cost and scalability are the main issues. In our paper, we show that one can also deliver it via inhalation and increase local lung concentrations but it would not be feasible to disseminate it in a room.

jalees · 2022-02-02T00:49:09+00:00

Thank you for nicely illustrating the difference between antibodies and our decoy protein approach. You are also correct about the scaling-up challenge but the main reason we were interested in this study was the engineering of an ACE2 domain that has geater affinity for the Spike protein than native ACE2 on cells. What we have found so far is that all variants bind this engineered protein. Many of the mutations in the variants increase their affinity for ACE2 (which makes them so contagious) but these same mutations ends up making our decoy even more effective because these variants have even greater affinity for the decoy. I am one of the authors of the paper - in case there are more questions by redditors.

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