The two children of Gautam Dongre in India and the son of Pascazia Mazeze in Tanzania live with an inherited blood disease that turns blood cells into instruments of pain.
With new gene therapies promising a cure for their sickle cell disease, Dongre says he is “praying for the treatment to come to us.”
But experts say the one-time treatment is out of reach in India and Africa, places where the disease is most common. Major inequalities have cut off much of the world from gene therapy in general.
While access to all kinds of medicines is limited in developing countries, the problem is especially acute for these therapies, which are among the most expensive treatments in the world.
In addition to the sky-high prices, these therapies are extremely complex to deliver 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 disease have only been approved in wealthier countries: both in the US, and one each in Britain and Bahrain.
“The vast majority of patients live in an area where they do not have access to this type of therapy,” says 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, need to think about that.”
Access to gene therapies was a key focus at this year’s International Summit on Human Genome Editing in London. A subsequent editorial in the journal Nature said high prices are “completely failing” low- and middle-income countries and could hinder 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 disease will remain a distant dream.
FIGHTING FOR BASIC TREATMENT
For gene therapy to even be an option, people in developing countries must survive long enough to receive it. There, sickle cell disease is more likely to cause disability or be fatal than in wealthy areas. Late diagnosis is common and basic care can be difficult to obtain.
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 its attack on the body at birth, affecting hemoglobin, the protein in red blood cells that transports oxygen. 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 cure 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 put the number at between 6 and 8 million. It is more common in areas prone to malaria because carrying the sickle cell trait helps protect against severe malaria. Research shows that more than one million people live with sickle cell disease in India, and more than five million in sub-Saharan Africa.
Dongre, who lives in Nagpur in central India, has seen the struggle in his own family and among the people he has met as leader of the National Alliance of Sickle Cell Organizations in India. For years, awareness of the disease was lacking, he said, even among some health care workers.
Dongre recalled how his newborn son Girish cried constantly due to stomach and leg pain. Doctors couldn’t figure out what was wrong and didn’t diagnose him with sickle cell disease for 2 1/2 years. When their daughter Sumedha was born, he and his wife immediately had her tested and discovered that she too had the disease.
Other patients remain undiagnosed for ten years or more. Lalit Pargi, who lives in Udaipur in northern India, said he was not diagnosed until he was 16, despite having the telltale yellow eyes and skin of jaundice, a common sign of sickle cell disease. That meant a childhood full of inexplicable pain.
‘GOD AND GOOGLE’
Available treatments can reduce the attacks of pain known as ‘crises’. Dongre’s children, now 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 controls the disease. Both have been hospitalized for bouts of pain, especially when they were younger.
Other patients in rural areas die at a very young age without receiving proper treatments, Dongre said.
In July, Indian Prime Minister Narendra Modi launched a sickle cell elimination mission that combines awareness, education, screening, early detection and treatment. Dongre praised the efforts but said the country faces major obstacles to achieving its goals.
The situation is much the same in East Africa’s Tanzania, where the health ministry is working with pharmaceutical company Novartis, which makes sickle cell drugs, to improve access to diagnosis and treatment.
Mazeze searched 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. “Afterwards I was praying. It was God and Google.”
Her son is now 10 and takes hydroxyurea and folic acid for anemia. They’ve helped, but haven’t eliminated pain attacks like the one that put him in the hospital for two weeks earlier this year.
Yet Mazeze considers herself lucky that she can afford treatment at all.
“We have people in Tanzania who can’t even handle folic acid,” she said. “One month’s worth of folic acid costs 1,000 Tanzanian shillings – less than a dollar,” while out-of-pocket costs for hydroxyurea can be more than 35 times as much.
‘IMPORTANT CHALLENGES’
Such grim realities make the cost of gene therapies an insurmountable obstacle, experts say. The price tags for the two sickle cell therapies in the US are $3.1 million and $2.2 million, although costs for gene therapies can vary by country.
The process of delivering the therapies is just as big a hurdle.
Patients must go to the hospital, where stem cells are removed 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 switch off a gene. The cells should 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 getting their changed cells back via IV, and spend weeks in the hospital. The process can take months.
“The infrastructure doesn’t exist to make this possible in many parts of the world,” says Dr. David Altshuler, Chief Scientific Officer at Vertex. “There is a great unmet need, but there are also great challenges.”
Not only do many medical centers lack things like specialized equipment, but the health care systems themselves are relatively skeletal. For example, World Health Organization data shows that India and Tanzania both have less than a quarter of the hospital beds per capita in the US.
Scientists say one possible solution — although not an immediate solution — 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 the need for chemotherapy, which carries serious risks such as infertility. His team is working to create a pill that would not edit genes but would serve the same purpose: helping the body produce a fetal form of hemoglobin, since the adult form is defective in people with sickle cell disease.
Other scientists are also working on simpler possible treatments, 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, such as pills, will necessarily be affordable.
“Someone is going to want to be compensated for developing that pill,” although foundations could help bring the pill to developing countries, said the Harvard Medical School pediatrics professor, who is paid by the Howard Hughes Medical Institute, which also makes The Associated supports. Health and Science Press Department. Experts say governments will also likely play an important role in getting patients a cure.
Dongre said he hopes gene therapy for sickle cell disease eventually reaches India. If so, he would like his children to be among the first to get it. Mazeze said she may wait to see how other patients fare, but she will consider it for her son as well.
Both agreed that patients in all countries – rich or poor – should have a choice.
“We are all part of one single planet,” Dongre said.
___
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.