Dr. Prithu Sundd Working to Cure Sickle Cell Disease

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According to the Center for Disease Control, it is estimated 1 in 13 African Americans are born with the genetic trait that can cause sickle cell disease (SCD). In Wisconsin, approximately 85% of SCD patients live in the southeastern region of the state.  

Sickle Cell Disease is an inherited blood disorder characterized by abnormal hemoglobin, a protein that helps red blood cells carry oxygen throughout the body. People with sickle cell disease have a mutation in the gene that produces hemoglobin, causing their red blood cells to become rigid and crescent or sickle-shaped instead of the normal round shape.

These rigid cells have difficulty passing through small blood vessels, leading to blockages that can cause pain and organ damage. Affecting both women and men, sickle cell disease is commonly found in people of African descent. Although curative therapies have been recently introduced, the access to these therapies remains limited, but ongoing research in medical care offers hope. For instance, early diagnosis through newborn screening programs can enhance the quality of life for sickle cell disease sufferers.

As the principal investigator running a sickle cell disease lab, Dr. Prithu Sundd is investigating sickle dell blood disorders. I caught up with him at the Versiti Blood Research Institute and Blood Center of Wisconsin, part of the broad complex of Medical College of Wisconsin and Milwaukee Regional Medical Center buildings in Wauwatosa. His blood research work has been cited by hundreds of publications, and he has written or co-written more than 50 articles. 

A half hour into my interview with Sundd, I realized I had entered the mind of this accomplished research scientist, and my brain was straining.

You grew up in India. Where did you spend your childhood? What were your parents like? And why did you end up moving to the United States?

I was born in Varanasi, India in the plains below the Himalayas, one of the oldest cities in the history of civilization. Varanasi is now a popular tourist destination. My father was an environmental scientist working for a government agency. I graduated from St, John’s School, a convent high school. For college, I went to Harcourt Butler Technology University and got my bachelor’s degree in biochemical engineering. After that, I worked for one year in a big Indian beer brewing company, United Breweries Ltd. But I wasn’t interested in being a beer brewer.

How did you come to settle in the United States? 

I started my Ph.D. program at Ohio University in Athens, Ohio. I learned how cells interact in blood vessel walls and with platelets. I graduated with my Ph.D in Fall 2007, and I moved to La Jolla, California to study at the La Jolla Institute of Immunology as a postdoctoral fellow. Over the five years there, I published two landmark and several other articles. In beginning of 2013, I was invited to the University of Pittsburgh as an assistant professor of medicine and bioengineering, then later promoted to associate professor with tenure. Until 2013, I was studying how white blood cells and platelets do their jobs in blood vessels. In 2013, I began to study sickle cell disease. Six months ago, I took this job at the Versiti Blood Research Institute as the senior investigator in the thrombosis and hemostasis program. 

You are also head of the sickle cell disease SCD lab. What does the Versiti Blood Research Institute do? 

We study sickle cell disease, which is now also recognized as an immune disorder. The patients’ white blood cells attack the body because they respond to antigens generated by patients’ own body. In other words, your cells react as if you had an infection, but you do not have an infection. In the last decade, we and other scientists found that sickle red blood cells break open to release hemoglobin, which in turn results in organ injury and causes blood cells to bind to other cells, causing the occlusion or blockage of the blood vessels. This causes inflammation.

According to the Versiti Blood Research Institute webpage, sickle cell disease is an inherited condition that affects one out of every 400 African American births. The symptoms of sickle cell anemia are a yellowish color of the skin (jaundice) or whites of the eyes (icterus) that appear when a large number of red cells undergo hemolysis, extreme tiredness from anemia, and painful swelling of the hands and feet.

We call this pain crisis. A few days later, the patient might have respiratory failure. The patient is put on transfusions, which might make improvements. But there is no therapy they can take at home to avoid the crisis. Along with the pharma companies, we are working on rescue therapies. The health care costs can be $3 billion for these patients in the United States, mainly because of frequent emergency room and hospital visits. The jaundice-like appearance is caused by excessive anemia. Dactilytis is the painful swelling of hands and feet caused by blockage of blood vessels and affects primarily infants or toddlers suffering from sickle cell disease.

If a patient is diagnosed with sickle cell disease, how much time do they have to live?

The data says the medium lifetime expectancy is 45, but some can live into their 60s with therapies like hydroxyurea and blood transfusions.

I understand that sickle cell disease is an inherited disease.

Yes, it is an inherited genetic disease. The mutation probably happened 20,000 to 25,000 years ago in west Africa when it was a wetland, not a desert, and the land was being cultivated for crops, and malaria was rampant. Currently, there are 100 to 200 million carriers of the sickle cell gene on this planet. Most are asymptomatic and nothing happens.

How old would someone be when they can first recognize the symptoms of sickle cell disease?

The disease starts happening after three months of birth. If you have two copies of the mutation in your hemoglobin, when your blood flows through your body, it gives oxygen to tissues, but as it deoxygenates, this hemoglobin tends to form rod-like structures and becomes stiff causing red blood cells to take sickle shape. 

Because sickle cell disease is an inherited disease, if I am diagnosed as positive, would you advise me not to have children?

In the United States, we do not do that. But there is a voluntary counseling process available to parents who are carriers. Currently, every baby is screened for sickle cell disease. On a global scale, there are 8 million people who have tested positive for sickle cell disease, which is the 12th major cause of death among children zero to five years old. More than half of those children live in Africa. 

Let me quote you, “Our goal is to understand how innate immune signaling in neutrophils and platelets contributes to morbidity of sickle cell disease.” Can you translate this concept into common terms readers can understand?

Neutrophils and platelets are the innate immune cells in your blood. 60 to 80% of your blood cells are neutrophils, which are the cells that heal a scratch. We try to understand how these cells cause blood vessel occlusion and respiratory failure in sickle cell disease. If you know how it happens, then you can create therapies to stop it.     

If you have the Sickle Cell Disease, what happens with the red blood cells?

The red blood cells contain the mutated hemoglobin, which forms stiff rod-like structures that are needle-like. As a result, red blood cells become stiff and can get stuck and break in the bloodstream, releasing the hemoglobin. This stiffening also works the red blood cells into a kind of dent. These dents stick to the white blood cells, platelets, and blood vessel walls. Remember that red blood cells contain hemoglobin which can bind to oxygen in the lungs and take the oxygen to different parts to the body. 

If I am a child and diagnosed with sickle cell disease, what is the treatment process?

You would be taking Hydroxyuerua from an early age. Your spleen’s job is to clear damaged red blood cells. Overtime, spleen function will drop to overload of removing damaged cells and by the time you are an adult, you most likely will have no spleen function left. Most patients have a low-grade chronic pain and occasional episode of severe acute pain requiring emergency treatment.

Here is a quote from you, “African Americans should be more forthcoming in donating blood to blood banks. Most patients, because of donations, end up getting Caucasian blood, which leads to an elevated response, and patients end up getting more sick. We need African Americans to come forward so the therapy can be more meaningful.” Why are African Americans reluctant to donate blood?

There is an element of mistrust among African Americans when it comes to health treatment. Some believe they will be treated unfairly. Many don’t like donating their blood. But we do need more blood donations from African Americans. When we test a drug in the lab, we need to make sure we have a race-matched blood sample from someone who does not have the disease. In healthcare, patients get blood transfusions. To sustain one patient, you cannot take blood from the same donor every day. To sustain that patient over one year, you need at least ten race-matched healthy controls with the same blood types. Over 50% of African Americans have type Ro blood. I am appealing to African Americans to donate blood.

You are the senior investigator in your sickle cell blood lab. What are your responsibilities?

We are looking mainly at how to prevent lung injury and respiratory failure and blood clotting in the lungs. 

Your lab team consists of accomplished post-doctoral researchers. Are these scientists assigned a specific task?

They are assigned specific questions to answer. One scientist might look at xyz mechanism in neutrophils, the causes, how he can silence that. Another scientist might be looking at blood clotting. Another could be studying platelets. We are trying to dial down symptoms enough to keep patients safe from infection. We also do research with mice models which express human sickle cell disease. We work with Pharma companies on a regular basis, exchanging test results. We have a long way to go, but there has been progress.

Symptoms of sickle cell anemia can vary in severity and may include:

•Pain Crises: Episodes of severe pain, often in the bones, chest, abdomen, or joints, caused by blocked blood flow.

• Anemia: Fatigue, weakness, pale skin, and shortness of breath due to a reduced number of healthy red blood cells.

• Organ Damage: Sickle cells can damage organs such as the spleen, kidneys, lungs, and liver over time, leading to complications like organ failure.

• Infections: People with sickle cell anemia are more susceptible to infections due to loss of spleen function.

• Stroke: Caused by blocked blood vessels or blood vessel shape change leading to reduced blood flow in the brain.