by The two children of Gautam Dongre 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 anemia, Dongre says he is “praying that the treatment comes to us.”
But experts say the one-size-fits-all treatment is out of reach in India and Africa, places where the disease is most common. Large inequalities prevent much of the world from accessing gene therapy in general.
While access to all types of medicines is limited in developing countries, the problem is especially serious with these therapies, which are among the most expensive treatments in the world.
Beyond their sky-high prices, these therapies are extremely complex to administer to patients because they require long hospital stays, sophisticated medical equipment, and specially trained doctors and scientists. So far, the two gene therapies for sickle cell anemia have only been approved in wealthier countries: both in the United States and one also in Britain and Bahrain.
“The vast, vast majority of patients live in an area where they don’t have access to this type of therapy,” said Dr. Benjamin Watkins, who treats sickle cell disease in New Orleans and is also involved in pediatric work internationally. “We, as medical professionals and as a society, have to think about that.”
Access to gene therapies was a major topic at this year’s international summit on human genome editing in London. A subsequent editorial in the journal Nature said high prices leave low- and middle-income countries “completely in the lurch” and could hamper progress across the field.
Some scientists worry that new cures will not reach their potential, that future treatments may never be invented and that the prospect of eradicating diseases like sickle cell anemia remains a distant dream.
FIGHT FOR BASIC TREATMENT
For gene therapy to even be an option, people in developing countries must stay alive long enough to receive it. There, sickle cell anemia is more likely to disable or kill than in wealthy regions. Late diagnosis is common and basic care can be difficult to obtain.
While gene therapy “is a huge advance … we can’t forget about those patients,” said Watkins, of Children’s Hospital of New Orleans.
Sickle cell anemia begins its attack on the body from birth and affects hemoglobin, the protein in red blood cells that carries oxygen. A genetic mutation causes cells to become crescent-shaped, which can block blood flow and cause problems such as excruciating pain, organ damage and stroke.
The only other cure is a bone marrow transplant, which must come from a very compatible donor and carries a risk of rejection.
Global estimates of how many people suffer from the disease vary, but some researchers put the number between 6 and 8 million. It is more common in malaria-prone regions because having the sickle cell trait helps protect against severe malaria. According to studies, more than 1 million people with sickle cell anemia live in India, and more than 5 million are in sub-Saharan Africa.
Dongre, who lives in Nagpur, central India, has seen the struggles in his own family and among people he met as a leader of the National Alliance of Sickle Cell Organizations in India. For many years, awareness about the disease has been lacking, he said, even among some health professionals.
Dongre recalled how his newborn son, Girish, was constantly crying due to stomach and leg pains. Doctors couldn’t figure out what was wrong and didn’t diagnose him with sickle cell anemia for two and a half years. When his daughter Sumedha was born, he and his wife immediately tested her and discovered that she too had the disease.
Other patients go undiagnosed for a decade or more. Lalit Pargi, who lives in Udaipur, northern India, said she was not diagnosed until she was 16, despite having yellow eyes and skin telltale of jaundice, a common sign of sickle cell anemia. That meant a childhood full of inexplicable pain.
‘GOD AND GOOGLE’
Available treatments can reduce pain attacks known as “crises.” Dongre’s children, now 19 and 13, take a medication called hydroxyurea, a decades-old chemotherapy drug that helps prevent the formation of sickled red blood cells and control the disease. Both have been hospitalized for episodes of pain, especially when they were younger.
Other patients in rural areas are dying at very young ages without receiving proper treatments, Dongre said.
In July, Indian Prime Minister Narendra Modi launched a sickle cell “elimination mission” that combines awareness, education, early detection and treatment. Dongre praised the effort, but said the country faces enormous obstacles in achieving its goals.
The situation is very similar in Tanzania, in East Africa, where the Ministry of Health has partnered with the pharmaceutical company Novartis, which makes drugs for sickle cell anemia, to improve access to diagnosis and treatment.
Mazeze sought 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.”
Her son is now 10 years old and takes hydroxyurea and folic acid for anemia. They have helped, but not eliminated, bouts of pain like the one that put him in the hospital for two weeks earlier this year.
Still, Mazeze considers herself lucky to be able to afford the treatment.
“We have people in Tanzania who can’t even administer folic acid,” he said. “Folic acid for a month costs 1,000 Tanzanian shillings, less than a dollar,” while out-of-pocket costs for hydroxyurea can be more than 35 times more.
‘SIGNIFICANT CHALLENGES’
These stark realities make the cost of gene therapies an insurmountable obstacle, experts say. Prices for the two sickle cell therapies in the United States are $3.1 million and $2.2 million, although the cost of gene therapies can vary by country.
The process of administering therapies is an equally large obstacle.
Patients must go to the hospital, where stem cells are extracted from their blood in a process that requires specialized equipment. One treatment, made by Vertex Pharmaceuticals and CRISPR Therapeutics, involves sending the cells to a lab as quickly as possible to keep them fresh and using a gene-editing tool called CRISPR to turn off a gene. The cells must be returned to liquid nitrogen so that they remain frozen until ready to use.
The other therapy, made by Bluebird Bio, does not use CRISPR but involves the same process for patients. In both cases they must undergo chemotherapy before recovering their altered cells intravenously and spending weeks in the hospital. The process can take months.
“The infrastructure does not exist to make this possible in many parts of the world,” said Dr. David Altshuler, Vertex’s chief scientific officer. “There is a huge unmet need, but also significant challenges.”
Not only do many medical centers lack things like specialized equipment, but the healthcare systems themselves are comparatively skeletal. For example, World Health Organization data show that India and Tanzania have less than a quarter of the hospital beds per capita that the United States has.
Scientists say a possible solution, although not immediate, is to develop easier-to-administer versions of the new therapies. Altshuler said Vertex is trying to find ways to provide the same benefits without requiring chemotherapy, which carries serious risks such as infertility. His team is working on making a pill that would not edit genes but would have the same goal: helping the body produce a fetal form of hemoglobin, since the adult form is defective in people with sickle cell anemia.
Other scientists are also working on simpler potential cures, including Dr. Stuart Orkin, one of the scientists whose work led to the development of Vertex therapy.
Orkin said he’s not sure if next-generation treatments, like the pills, will necessarily be affordable.
“Someone is going to want to be compensated for the development of that pill,” although foundations could help bring it to the developing world, said the Harvard Medical School pediatrics professor, who is paid by the Howard Hughes Medical Institute. , which also supports The Associated Department of Science and Health Press. Experts said governments will also likely play a decisive role in getting cures to patients.
Dongre said he hopes gene therapy for sickle cell will eventually come to India. If so, he would like his children to be among the first to receive it. Mazeze said she may wait to see how other patients do, but she will consider it for her son as well.
They both agreed that patients in all countries (rich or poor) should have the 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 Educational Media Group. The AP is solely responsible for all content.
