Gautam Dongre’s two children in India and Pascazia Mazeze’s son in Tanzania live with an inherited blood disorder that turns blood cells into instruments of pain.
Now that new gene therapies promise a cure for sickle cell disease, Dongre says he’s “praying for the cure to come to us.”
But experts say a one-time treatment is out of reach in India and Africa, where the disease is most common. Huge inequalities mean that large parts of the world are generally excluded from gene therapy.
While access to all kinds of medicines is limited in developing countries, the problem reaches especially serious levels in these treatments, which are among the most expensive in the world.
Beyond their sky-high prices, these treatments are extremely complex to administer to patients because they require long hospitalizations, advanced medical equipment, and specially trained doctors and scientists. So far, two gene therapies for sickle cell have been approved only in richer countries: both in the US and one in Britain and Bahrain.
Dr., who treats sickle cell in New Orleans and is also interested in pediatric studies internationally. “The vast majority of patients live in an area where they do not have access to these types of therapies,” said Benjamin Watkins. “We, as medical professionals and as a society, need to think about this.”
Access to gene therapies was a key focus of this year’s international summit on human genome editing in London. A later editorial in the journal Nature noted that high prices leave low- and middle-income countries “completely stranded” and could hinder progress in this field.
Some scientists worry that new treatments may not live up to their potential, that future treatments may never be invented, and that the possibility of eradicating diseases such as sickle cell will remain a distant dream.
WE FIGHT FOR BASIC TREATMENT
For gene therapy to be an option, people in developing countries need to survive long enough to receive it. Sickle cell disease is more likely to maim or kill there than in affluent areas. Late diagnosis is common and basic care can be difficult to achieve.
While gene therapy “is a huge step forward … we can’t forget about these patients,” said Watkins, of Children’s Hospital New Orleans.
Sickle cell disease begins attacking the body from birth and affects hemoglobin, the protein that carries oxygen in red blood cells. A genetic mutation causes the cells to become crescent-shaped, which can block blood flow and cause problems such as excruciating pain, organ damage and stroke.
The only other treatment is a bone marrow transplant, which must come from a closely matched donor and carries the risk of rejection.
Global estimates of how many people have the disease vary, but some researchers estimate the number to be between 6 and 8 million. It is more common in malaria-prone areas because carrying the sickle cell trait helps protect against severe malaria. Studies show that more than 1 million people with sickle cell disease live in India and more than 5 million live in sub-Saharan Africa.
Dongre, who lives in Nagpur in central India, has seen the struggles in his own family and among the people he meets as the leader of the National Alliance of Sickle Cell Organizations in India. He said awareness of the disease has been lacking for many years, even among some health professionals.
Dongre recalled how his newborn son Girish was crying constantly due to stomach and leg pain. Doctors couldn’t figure out what was wrong and didn’t diagnose him with sickle cell for 2 1/2 years. When their daughter Sumedha was born, she and her husband immediately had her tested and learned that she too had the disease.
Other patients remain undiagnosed for a decade or more. Lalit Pargi, who lives in Udaipur in northern India, said he wasn’t diagnosed until he was 16 despite having yellow eyes and jaundiced skin, a common symptom of sickle cell. This meant a childhood filled with inexplicable pain.
‘GOD AND GOOGLE’
Current treatments can reduce bouts of pain known as “crises.” Dongre’s children, now ages 19 and 13, take a drug called hydroxyurea, a decades-old chemo drug that helps prevent the formation of sickle-shaped red blood cells and control the disease. Both were hospitalized for attacks of pain, especially when they were young.
Dongre said other patients in rural areas also died at very young ages before receiving the right treatments.
In July, Indian Prime Minister Narendra Modi launched a sickle cell “eradication mission” combining awareness, education, screening, early detection and treatment. Dongre praised the effort but said the country faces major obstacles in achieving its goals.
The situation is much the same in East Africa’s Tanzania, where the health ministry has partnered with pharmaceutical company Novartis, which produces a sickle cell drug, to improve access to diagnosis and treatment.
Mazeze scrambled for information after her son Ian Harely was diagnosed.
“I Googled and Googled and I couldn’t sleep,” said Mazeze, executive director of the Tanzania Sickle Cell Warriors Organization. “After that I was praying. It was God and Google.”
His son is now 10 years old and is taking hydroxyurea and folic acid for anemia. They helped, but they couldn’t eliminate the episodes of pain that hospitalized him for two weeks earlier this year.
Still, Mazeze considers himself lucky to be able to afford the treatment.
“We have people in Tanzania who can’t even handle folic acid,” he said. “Folic acid for a month costs 1,000 Tanzanian shillings, or less than a dollar,” while out-of-pocket expenses for hydroxyurea can be more than 35 times that.
‘SIGNIFICANT CHALLENGES’
Such stark realities make the cost of gene therapies an insurmountable hurdle, experts say. The price tags for the two sickle cell therapies in the US are $3.1 million and $2.2 million, but the cost of gene therapies can vary by country.
The process of delivering therapies is equally a major hurdle.
Patients must go to the hospital, where stem cells are removed from their blood in a process that requires special equipment. One treatment, made by Vertex Pharmaceuticals and CRISPR Therapeutics, involves sending cells to the lab as soon as possible to keep them fresh and using a gene-editing tool called CRISPR to knock out a gene. The cells need to be returned in liquid nitrogen so they remain frozen until ready for use.
In the other therapy made by Bluebird Bio, CRISPR is not used, but the same process is applied for patients. In both cases, they must undergo chemotherapy and stay in the hospital for weeks before they can get their modified cells back through an IV. The process may take months.
Vertex’s chief scientific officer, Dr. “In many parts of the world, the infrastructure to make this possible does not exist,” said David Altshuler. “There is a huge unmet need, but there are also significant challenges.”
Not only do many medical centers have shortages such as specialized equipment, but their healthcare systems are also relatively weak. For example, World Health Organization data show that India and Tanzania have less than a quarter of the number of hospital beds per capita in the United States.
Scientists say one possible solution (though not an immediate one) is to develop easier-to-administer versions of new treatments. Altshuler said Vertex is trying to find ways to provide the same benefits without the need for chemotherapy, which comes with serious risks such as infertility. His team is working on a pill that wouldn’t change genes but would have the same purpose: to help the body produce the fetal form of hemoglobin, since the adult form is defective in people with sickle cell.
One of the scientists whose work led to the development of Vertex therapy, Dr. Other scientists, including Stuart Orkin, are also working on simpler potential treatments.
Orkin said he’s not sure whether next-generation treatments like pills will necessarily be cost-effective.
“Although foundations can help bring this pill to the developing world, someone is going to want to get compensated for developing this pill,” said the Harvard Medical School professor of pediatrics, who is paid by the Howard Hughes Medical Institute, which also supports The Associated. Health and Science Section of the Press. Governments will also likely be instrumental in providing treatment to patients, experts said.
Dongre said he hopes gene therapy for sickle cell will eventually reach India. If so, she wants her children to be among the first to receive it. Mazeze said he could wait to see how other patients fare, but he would also consider this for his son.
Both agreed that patients in all countries, rich or poor, should have this option.
“We are all part of one planet,” Dongre said.
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Education Media Group. AP is solely responsible for all content.