How gene therapy can boost treatment of sickle cell disease in Nigeria

By Ojoma Akor

Medical experts have said high-burden countries need increased investment in and adoption of new, advanced therapies for sickle cell disease, such as gene therapy and bone marrow transplants.

They said recent breakthroughs in medical research show that adopting gene therapy is important to reduce the burden of sickle cell disease and leave no one behind.

Gene therapy is a procedure in which specialists fix or replace a faulty gene to cure a disease or help the body fight it.

Sickle cell disease is a genetic blood disorder that affects a person’s red blood cells and is passed on from parents.

The disorder causes normal, round, flexible blood cells to become stiff and sickle-shaped, which in turn stops the blood cells and the oxygen they carry from moving freely around the body.

Nigeria is also ranked as the most sickle cell-endemic country in Africa; about 25 percent of Nigerian adults are healthy carriers of the sickle cell gene.

Many children are born with sickle cell disease every year in Nigeria. About 150,000 children are born annually with the disease in Nigeria, and 100,000 infants die from the disease, which is 8 percent of infant mortality, according to medical experts.

The country also has the highest burden of sickle cell disease in the world, ahead of India and the Democratic Republic of Congo.

People living with sickle cell disease in Nigeria live with excruciating pain, frequent hospital visits, and, along with their families, suffer under the burden of high treatment costs, poor health, and sometimes death.

Prof. Obiageli Nnodu, a hematologist and the director of the Center of Excellence for Sickle Cell Disease Research & Training (CESRTA),  said children born with the disease die early if they are not followed up with appropriate care.

She said the 2018 National Demographic and Health Survey showed that around 2% of Nigerians live with the disease, translating to an estimated about four million people.

 A patient’s experience with the treatment

A recipient of gene therapy treatment, Jimi Olaghere, said he received the treatment for sickle cell disease five years ago in the United States of America. Since then, he has been functionally cured of the disease.

He said, “Before I was born, my mom did not have access to prenatal screening. And fortunately, she was able to fly to the U.S. and get that prenatal screening done. That prenatal screening confirmed that I would have sickle cell disease, so my mother decided to give birth to me there.”

He said he lived with sickle cell disease for 35 years before undergoing gene therapy treatment in the US, adding that it has completely changed his life.

The Atlanta-based technology entrepreneur said he lived with pain crises and frequent emergency room visits but that today, he is ” virtually pain-free.”

He said, “And fast forward to 35 years after being born, I got fortunate to participate in a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based gene therapy trial that has completely changed my life. I have traveled around the world telling my story, but this is the most important destination: Nigeria, where I feel my story needs to be heard because this is where I am from. So I am just really excited to come home and really show the community the impact of these gene therapies and other curative therapies. From what my life was like to what my life is right now, I’m excited to share this story.”

He said that the treatment is, however, not a walk in the park, adding that it took him nearly a year to recover.

“But if you have lived with sickle cell disease, you have already survived worse,” he added.

Olaghere added that he has been able to climb Mount Kilimanjaro after gene therapy treatment.

Experts view

Prof. Jennifer Adair, co-founder of the Global Gene Therapy Initiative (GGTI) and a faculty member at the University of Massachusetts Chan Medical School, said there was an urgent need to introduce curative treatments such as gene therapy and bone marrow transplants in countries with the highest burden of sickle cell disease, such as Nigeria.

She said, ” Jimi has had a tremendous response following gene therapy treatment, including living mostly pain-free since that treatment happened. Since then, he has been thriving physically and trying to manage the emotional changes that come with such a large transition.”

Prof. Adair highlighted that it is important for those affected to see that curative options are not science fiction, but real and increasingly within reach.

She said, “It is so important for us to let people of Nigeria, especially those warriors who live here in-country, see the possibilities for curative therapies such as gene therapy and also bone marrow transplant as possibilities for a better future for themselves,” she said during the recent 5th Global Sickle Cell Congress in Abuja.

Explaining gene therapy treatment for sickle cell disease, Prof. Nnodu of the Center of Excellence for Sickle Cell Disease Research & Training (CESRTA)  said, “It is a type of treatment in which an abnormal disease-causing gene is taken out of a cell and replaced by a gene to correct the deficiency. It involves altering the genetic material within cells to correct underlying genetic defects. Sometimes a functional copy of a faulty gene is added, such as beta-globin A in sickle cell disease, to make non-sickle red cells, or by disabling a disease-causing gene.”

She further explained that in sickle cell disease, ” the gene that controls the switch to make adult hemoglobin is knocked out. Hence, the cell goes back to making fetal hemoglobin, which inhibits sickling so that the individual has fewer crises and fewer complications.”

On the benefits of gene therapy for sickle cell disease patients, she said gene therapy is transformational, reduces crisis frequency, and restores health and well-being.

“Gene therapy corrects the abnormal gene, reduces its production in the body, and restores the individual to health and normal living,” she stated.

She added that sickle cell disease exerts a huge economic burden for individuals and their families because of the catastrophic health expenditures that it poses due to frequent crises and complications involving many organ systems over the life course.

She said, “Some complications such as stroke and chronic kidney disease, chronic leg ulcers, and priapism also prevent an individual with sickle cell disease from making meaningful contributions to their families in various ways”

Also, Prof. Adair, who is also the vice chair of the Department of Genetic and Cellular Medicine at UMass Chan Medical School, said that, as a medical professional, she has witnessed the transformation in the lives of children and adults who have been offered the opportunity to undergo gene therapy and other curative treatments.

She said, ” Many of us have taken care of sickle cell patients for most of our careers, and we were certainly happy to see some of the incremental steps that have occurred in terms of improving outcomes for sickle cell disease. But in the last five to ten years, seeing this opportunity to apply science in a way that would allow the patient to be their own donor and conceivably have a long-term effect on controlling their sickle cell disease, at some point would have been almost unimaginable.”

She added that, to date, no gene therapy clinical trial for sickle cell disease has taken place in Africa, where most patients are.

Prof. Nnodu, who also chaired the 5th Global Sickle Cell Congress local organizing committee, said the large number of people affected by the disease underscores the need to integrate advanced therapies like gene therapy into Nigeria’s healthcare system.

Eligibility for gene therapy treatment 

Dr. Alexis Thompson, a physician-scientist at the Children’s Hospital of Philadelphia and a lead investigator in U.S. gene therapy trials

said current gene therapy clinical trials have focused on individuals between ages 12 and 35, adding that patients outside the age range could still benefit from the therapies.

She said eligibility factors include age, disease severity, organ health, and willingness to undergo intensive conditioning.

She said, “But with earlier screening and better interventions, more patients could become eligible over time.”

Alexis, who is also a former president of the American Association for Hematology, said fertility preservation is recommended before the procedure.

She said, “For individuals who have not had children, we recommend harvesting and freezing eggs or sperm before the procedure. While the risk of cancer is considered low—likely below 5%—the risk of infertility is significant enough to warrant precautionary measures.”

She also applauded gene therapy treatment, saying, “What was once unthinkable, using a patient’s own genetically modified cells to control or even cure sickle cell disease is now a reality.”

Dr. Thompson said that, like all other treatments, there were some  risks such as infertility, infection, and rare cases of cancer, but that “This isn’t for everyone, but for many, the promise of a life without crisis pain is worth the trade-offs.”

She added that most patients who participated in their trials traveled far away from home, even within the United States, to undergo gene therapy, adding, ” In the future, that should not be the case. They should be able to get these therapies in a way that actually does not require that they disrupt their lives as much as they have had to so far.”

Concerns over cost of treatment 

Despite its curative effects, concerns remain about equitable access to gene therapy treatments in Nigeria and other countries in Sub-Saharan Africa.

Before the recent advancement of gene therapy,  bone marrow transplant was the only cure for sickle cell disease.

Nigeria has had a center for stem cell therapy for sickle cell for some years, but most patients have not been able to access the treatment because of the high costs.

These concerns have also been raised for gene therapy because its current cost is beyond the reach of many patients and their families in Nigeria.

A mother of two children who have sickle cell disease said meeting the cost of hospital bills during crises has not been easy, not to talk of expensive treatments like bone marrow transplant and gene therapy.

Another patient, Ibrahim, said he first heard of the treatment in the news in 2023 when the FDA approved two gene therapy treatments.

While saying it is a silver lining for reducing the burden of the disease in the country, he said most sufferers and their families in Nigeria cannot afford the cost of treatment.

On affordability, Prof. Adair said government involvement through local production and training will help reduce the cost of gene therapy.

She said, ” So, this is the opportunity that governments have to invest locally. If the government invests in the local economy and local manufacturing of these approaches, it can be done much more affordably and within the scale of the economy in which it is operating.”

She acknowledged that the current cost of the gene therapy treatment Olaghere received ranges from $2 million to $3 million in the US.

However, she said the US cost does not reflect what it will cost in every country.

She said, ” It is important to note that the price of these drugs in the U.S. is not necessarily reflective of what it costs to make that drug.

“In the United States, we use something called a value-based pricing system. It reflects what the market can bear and also the value that the therapy adds to the patient and to society. We have to look at the economic factors that go into that price in the U.S. and scale them for the local economy.”

The medical expert cited  Uganda as an example, where the same therapy could be cost-effective at approximately $40,000, saying it represents a starting point for investment.

“We have been doing research over the last five years on how best to approach this. We have developed a cost-effective strategy in Uganda that will be part of new research.  “What we found is that if you take the gene therapy that Jimi received, which costs $2.2 million right now in the U.S., and you scale that for the local economy in Uganda, you get something that is just as cost-effective if it costs about $40,000 in the Uganda setting, so there is a big scaling there.

“Now, $40,000 is still a lot of money. We don’t think that will be the ultimate price. Still, it is a starting point that could be leveraged to give access to the patients  who could most benefit from  gene therapy now to help implement the clinical research and the access for patients moving forward.”

She also said Nigeria is part of the GGTI, a coalition of nations committed to building local capacity for research, regulation, and access to gene-based treatments.

She said Uganda, one of the first six countries in the network, has already passed legislation to support bone marrow transplants and gene editing.

She said the  GGTI also supports knowledge transfer, including training programs between Nigeria, India, and the U.S., and promotes access to technical information in local languages.

While saying Nigeria has the foundation for investments in gene therapy, such as clinicians, researchers, and patient advocates, among others,  she said, “We are working to support clinicians who want to learn how to manufacture and administer these therapies locally.”