Aminu Alibe

25 March 2019

Period 6

Synthesis Paper Rough Draft

Sickle Cell Anemia is an inherited blood disorder that causes a mutation in the DNA to

produce abnormal hemoglobin - reducing the body organs’ supply of oxygen. The amount of

people who have sickle cell increased throughout history in typically hot regions of the world,

like Africa, India, and the Middle East because of sickle cell’s resistance to malaria. Limited

historical human migration out of these areas contained the spread of sickle cell. In recent

history, the disease has spread to other areas of the world as a result of migration. The Sickle

Cell Disease Association of America estimates an average of 100,000 people living in the United

States with the disorder. While the life expectancy of patients with sickle cell has been lower

than the life expectancy of those without it, modern medications have seen the life expectancy

for people with sickle cell who live in developed countries go beyond 60 years. This is

unfortunately contrasted to people with sickle cell who live in developing countries, where 90%

of children with sickle cell die before their fifth birthday. In order for extensive progress to be

made towards the alleviation of these adverse effects, such as ‘traditional’ or ‘silent’ stroke,

researchers must focus on gene therapy, developing new medicines, and distributing them to

those in areas of Africa and Asia where Sickle Cell is common.

Sickle Cell effects can affect the brain’s supply of oxygen. If the brain is deprived of

oxygen for enough time, a traditional or silent stroke can occur, which can impact other areas of

a person’s life. Traditional strokes are easier to spot because they have conventional symptoms,

meaning they could potentially be addressed before causing major damage. Silent strokes affect a
person’s physical health as well as a person’s cognitive abilities, which could result in poorer

academic performance and a lower intelligence quotient (Estcourt et al., n.d.). Silent cerebral

ischemia, or silent stroke, is potentially a more dangerous form of a stroke because it can be

undetected and adjust the brain’s white matter. Importantly, patients with sickle cell anemia are

more likely to have either silent or traditional strokes as a result of a blood clot forming and

blocking off oxygen supply to the brain (Coloigner et al., n.d.). A new technique, called diffusion

tensor imaging, or DTI, could be able to analyze the brain’s white matter, potentially providing a

way for doctors to monitor silent strokes (Issar, Nehra, Singh, & Issar, n.d.). When analyzed with

DTI, people with Sickle Cell suffered potential axonal damage (Issar, Nehra, Singh, & Issar,

n.d.). The effect of a silent stroke depends on which area of the brain was impacted. A person’s

speech, memory, and motor skills may be altered (“Could a Silent,” 2012). Silent strokes affect a

person’s physical health as well as a person’s cognitive abilities, which could result in poorer

academic performance and a lower intelligence quotient (Estcourt et. al., n.d.). There are

potential steps a person can take to mitigate his or her risk of a silent cerebral ischemia. For all

patients, researchers found ways to reduce the risk of a silent stroke include reducing blood

pressure and cholesterol, as well as having regular checkups with a doctor (“Reduce Your,”

2015). For Sickle Cell patients, researchers found that long-term blood transfusions could

prevent a silent stroke because it increased the amount of oxygen found in the red blood cells.

Transfusions reduced the frequency of acute chest syndrome and vaso-occlusive crisis (Estcourt

et al., n.d.). However, no difference was noted in children who already suffered from silent

cerebral ischemia.

Scientific advances in the field of gene therapy is a potential field that must be further

researched when looking for a cure for sickle cell anemia. Sickle cell disease has been identified
by researchers as a potential disease that can be cured by gene therapy with further research.

Sickle Cell disease is a candidate for gene therapy because it would only involve manipulating

one amino acid in the “β-globin” gene of DNA (Gammon, n.d.). However, complications arise

from harvesting stem cells from a patient because stem cells cannot be enticed to enter the

bloodstream because it increases the risk for a sickle cell crisis, so researchers must obtain them

from the bone marrow (Gammon, n.d.). This method would be done by taking stem cells from a

patient’s body, editing them, and reintroducing them to the body. A specific form of gene editing

that the author looks at is CRISPR-Cas9, which involves the Cas9 enzyme ‘cutting out’ portions

of the DNA, allowing them to be replaced. If successful in the future, this cure would provide a

cure for those living in the wealthier countries who suffer from sickle cell disease (Weintraub,

n.d.). Some researchers have even proposed gene therapy as early as in the womb. Researchers

who conducted studies have had success in dogs with the canine equivalent of sickle cell anemia.

The potential for this treatment still has a long way to go (“Healed in the Womb.”, n.d.).

Another treatment is already developed, however it requires stark tradeoffs in order to be

successful, involving taking medication to ensure the body does not reject a donor’s bone

marrow. This cure is only viable for 10% of people that have Sickle Cell Anemia because it

involves having a donor (Weintraub, n.d.). In another potential treatment, researchers have begun

trials to develop a drug that would further mutate a person’s genes in order to keep fetal

hemoglobin production up. So far, the trials present another tradeoff for parents. In order for the

drug to work, it would require strong chemotherapy that presents problems for the patient, such

as a risk of cancer in the future (Weintraub, 2016).

Aside from curing Sickle Cell Anemia, which researchers say may take a long time,

doctors are focused on addressing or preventing the symptoms that arise with Sickle Cell
Anemia, as well as quality of life. For example, researchers have discovered that certain drugs

reduce the pain in people with Sickle Cell Anemia. Researchers discovered that people with

sickle cell have a heightened sensitivity to temperature and pain because of the CaMKIIα

enzyme. Researchers tried using a drug that inhibits CaMKIIα in a trial of 18 patients and found

that 8 felt 50% less pain (Nogrady, n.d.). A long-term concern with managing sickle cell anemia

is the rigorous annual visits to a hospital that should be adhered to. They include at least 3-4

visits to monitor blood toxicity attributable to the drug hydroxyurea, a transcranial doppler scan

(TCD) to monitor for overt strokes, a visit to an opthamologist, and biannual oral hygiene

checkups (DeBaun, 2014).

Starting from the late 20th century, doctors and researchers have made huge strides in

helping people with Sickle Cell Anemia, starting by finding medications that can be taken to

prevent red blood cells from adopting a sickle shape and continuing with the development of a

greater understanding of how sickle cell affects the organs of the body. Doctors are now able to

treat side effects that arise as a result of sickle cell anemia, such as strokes, improving the quality

of life of people with sickle cell. However, more progress must be made. Especially in

developing countries, where a lack of access to quality healthcare sees people with sickle cell die

younger and at a higher rate. One major problem the developing world faces in relation to sickle

cell treatment is a lack of awareness among people about sickle cell anemia. Graham Serjeant, a

physician living in Jamaica that works to help the local population by providing free-screening

for people with sickle cell anemia. He notes that another major problem in fighting sickle cell

anemia is a lack of political motivation to dedicate resources towards proper healthcare.

Recently, three Indian states developed sickle cell programs to assist their citizens with the

disease. Should patients with sickle cell have a better quality of life, more governments in
countries with a larger sickle cell population must dedicate resources towards fighting the

disease.