Clinical trails of gene therapy are starting to show improvements for sickle cell anemia

    

 According to an article in the New York Times, there have been advancements in gene therapy for those suffering from sickle cell anemia. The article discusses the journey of a specific patient named Helen Obando who was the first Am6erican teenager to become sickle cell free from these clinical trails. The technique used as of late to treat sickle cell anemia is a bone marrow transplant from someone who does not have the disease and is a close enough match. However, there are cases in which a match cannot be found (like Obando's). 

    There are three types of clinical trials involving the treatment of the disease using gene therapy. The first, being the trial Obando underwent, used the technique to turn off her adult gene used to form hemoglobin and turn on her fetal one. The reason behind turning on the fetal gene is due to its inability to carry the sickle cell gene whereas the adult gene does. This allows perfectly formed red blood cells to be produced if the trial is successful. The second trial applied by Vortex used CRISPR in order to turn on and off those specific genes. CRISPR is used to target specific genes within the DNA and is a great technique when used to point out the hemoglobin producing gene. The third trial is being produced by Bluebird Bio which uses an inactive virus to give to the patients that held the appropriate hemoglobin gene. Unfortunately, Bluebird Bio had to pause its trial because two of its patients developed cancer.

    The unfortunate truth about sickle cell anemia is that the African American population are primarily born with the disease. Due to this commonality of the disease between African Americans, the progress for finding new methods for a cure have been happening slower than what may occur for non-minority groups. The reasoning behind this is up to opinion, but I think it is worth a conversation to have and that our heath care system may need to take a step back to reevaluate their focus. 

Sickle Cell Disease gene therapy

 

In this article I came across, the main topic discussed was Sickle Cell Disease. Sickle Cell is caused by a genetic defect that causes normally pliable red blood cells to become hard and sticky, this causes it to form a C-shape, like a sickle. It is an inherited red blood cell disorder, in which there isnt enough healthy red blood cells to carry oxygen. The abnormal blood cells often die early, causing anemia and clots in small blood vessels. The clots have the possibility of triggering a wide range of painful and life-threatening complications. In order to have this disease, it must be inherited from the parents. The article mentions how researchers are mentioning gene therapy treatments for Sickle cell, a pair of new gene therapies promise a potential lasting cure by subtly altering the genetic information in a patient's bone marrow cells. I think that having a possible long-lasting cure is a huge step in the right direction, although not everyone develops symptoms, this will be helping those who suffer from periodic episodes of pain, swelling, and frequent infections. 

https://www.usnews.com/news/health-news/articles/2020-12-05/could-gene-therapy-cure-sickle-cell-disease-two-new-studies-raise-hopes

https://www.cdc.gov/ncbddd/sicklecell/facts.html

Sickle Cell Against Malaria

Sickle Cell is a recessive inherited trait caused by a mutation in the hemoglobin-beta gene on chromosome 11. The disease causes red blood cells, to be abnormal (crescent shaped). 

Normal and Sickle red blood cells

An article published by ScienceDirect notes that Sickle human hemoglobin (Hb) can actually protect against malaria. The article notes that people that are heterozygous for the sickle cell gene, show a survival advantage in areas where malaria is prevalent. The disease in fact does not prevent the host from developing the parasite, but makes it tolerant to it. Individuals with sickle cell accumulate cell free hb and heme (non-protein part of hb) in the plasma which induces the expression of heme oxygenase-1. This enzyme catalyzes heme into other molecules including carbon monoxide, which binds to sickle hb and prevents it from releasing more heme and hence the pathogenesis of experimental malaria. 

Specialists think that the mechanism involving sickle hb is similar to other genetic blood diseases that also seem to provide  a type of protection to the host. These findings provide a great advantage and open ways to new therapeutic inventions against malaria.

Protein's Effect On Blood Cancer

The amino acid Valine has just been found to be a key factor in the formation of blood stem cells. In a recent study by researchers at Stanford University and the University of Tokyo mice deprived of this amino acid for two to four weeks completely stopped making new blood cells. It was found that Valine plays a key role in forming blood cells in humans as well. This finding could have major implications for transplant and leukemia patients. If deprived of protein before a bone marrow transplant, the deprivation would have the same effect the pre transplant chemotherapy has on these patients, killing/stopping all of their blood cells from forming to prepare them for their transplanted blood cells. The head researchers in this study also think that depriving leukemia patients of valine could kill of the cells that are causing their cancers. Deprivation of valine can be achieved from depriving patients of protein through an IV infused diet. Research has to be done to find out how long humans would have to be deprived of valine to completely stop their blood stem cell formation to see if it is a viable option to keep patients on an IV infused diet for the length of time necessary.

The deprivation of Valine could also be used to consider new candidates for bone marrow transplant, like pregnant women, who are not generally candidates because of the pre transplant use of chemotherapy.

Evolutionary change in humans?

The Tibetans live at altitudes of about 13,000 feet. The higher the altitude, the harder it is to breathe. This is because at an elevation of 13,000 feet, the air has 40% less oxygen compared to what is available at sea level. However, the Tibetans suffer from very little sickness.




To figure this problem out, researchers compared the genomes of the Tibetans and the Han chinese, which happen to be the two majority ethnic groups in China. The biologist found 40 genes that had undergone mutation or evolutionary change that allowed the Tibetans to adapt to the high altitude. The two groups split apart about 3,000 years ago.

If this holds true, this would be the most recently known example of evolutionary change in humans. When lowlanders try to adjust to the high altitudes, their blood thickens which causes the body to overproduce red blood cells. As a result, this causes mountain sickness which leads to lesser fertility.

I personally find this stuff fascinating. Later in the article it mentions that they think that natural selection played a role as more and more offspring were thrown into the population. However, I am in awe of what the human body is capable of. The way that it can heal itself and change in order to survive is taken for granted, I think.