by Both children of Gautam Dongre in India and Pascazia Mazeze’s son in Tanzania have 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 that the cure should 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. Huge imbalances reduce much of the world from gene therapy in general.
Although access to all types of medicine is limited in developing countries, the problem is particularly acute with these therapies, which are among the most expensive treatments in the world.
Apart from their sky-high prices, these therapies are extremely complicated to administer to patients as they require long hospital stays, sophisticated medical equipment and specially trained doctors and scientists. So far, the two gene therapies for sickle cell have only been approved in rich countries: both in the US, and one in Britain and also in Bahrain.
“The vast majority of patients live in an area that doesn’t have access to this type of therapy,” said Dr. Benjamin Watkins, who treats sickle cell 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 focus 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 a lurch” and could hinder progress across the board.
Some scientists are concerned that new medicines will never reach their potential, that treatments may never be devised in the future and that the prospect of eradicating diseases such as sickle cell will remain a distant dream.
STRUGGLING YOUR BASIC TREATMENT
For gene therapy to even be an option, people in developing nations need to live long enough to receive it. Sickle cell disease is more likely to disable or kill than in affluent regions. Late diagnosis is common and access to basic care is difficult.
Although gene therapy is a big step forward … we can’t forget about those patients,” said Watkins, of Children’s Hospital, New Orleans.
Sickle cell disease begins to attack the body at birth, affecting hemoglobin, the protein in red blood cells that carries oxygen. A genetic mutation causes the cells to become sickle-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 a risk of rejection.
Global estimates of how many people have the disease vary, but some researchers put the number between 6 million and 8 million. It is more common in regions prone to malaria as carrying the sickle cell trait helps protect against severe malaria. More than 1 million people with sickle cell disease live in India, studies show, and more than 5 million in sub-Saharan Africa.
Dongre, who lives in Nagpur in central India, saw the struggles in his own family and among people he met as the leader of the National Alliance of Hemp Cell Organizations in India. For many years, there has been a lack of awareness of the disease, he said, even among some health professionals.
Dongre recalled how his newborn son Girish was constantly crying due to stomach and leg pain. The doctors couldn’t figure out what was wrong and they went undiagnosed with sickle cell disease for 2 1/2 years. When their 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 in northern India, said he was not diagnosed until he was 16, despite having yellow eyes and jaundiced skin, a common sign of sickle cell. That meant a childhood filled with inexplicable pain.
‘GOD AND GOOGLE’
Available treatments can reduce pain known as “crisis.” Dongre’s children, now 19 and 13, take a medicine 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 episodes of pain, especially when they were younger.
Other patients in rural areas are dying at very young ages without receiving the proper treatments, Dongre said.
In July, Indian Prime Minister Narendra Modi launched a sickle cell “eradication mission” that combines 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 Tanzania in East Africa, where the health ministry is partnering with the drug company Novartis, which makes sickle cell medicine, to improve access to diagnosis and treatment.
Mazeze was looking for information after her son, Ian Harely, was diagnosed.
“I Googled and Googled and I couldn’t sleep,” said Mazeze, executive director of the Tanzanian 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 helped, but didn’t stop episodes of pain like the one that put him in the hospital for two weeks earlier this year.
However, Mazeze considers herself lucky to be able to receive treatment at all.
“We have people in Tanzania who can’t even manage folic acid,” she said. “Folic acid for a month is 1,000 Tanzanian shillings – less than a dollar,” and out-of-pocket costs for hydroxyurea can be more than 35 times that.
‘SIGNIFICANT CHALLENGES’
Such harsh 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 the cost of gene therapies can vary by country.
The process of administering the therapies is such a hurdle.
Patients must go to hospital, where stem cells are extracted from their blood in a process that requires specialized equipment. One treatment, developed 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 knock out a gene . The cells must be sent back in liquid nitrogen so that they remain frozen until they are ready to be used.
The other therapy, made by Bluebird Bio, does not use CRISPR but involves the same process in patients. In both cases they have to undergo chemotherapy before getting their changed cells back by IV, and spend weeks in hospital. The process can stretch for months.
“The infrastructure to do it is not there in many parts of the world,” said Dr. David Altshuler, chief science officer at Vertex. “There is a huge unmet need, but there are also significant challenges.”
Not only do many medical centers lack things like specialized equipment, but the health care systems themselves are quite skeletal. For example, World Health Organization data shows that India and Tanzania have less than a quarter of the hospital beds per-capita of the US.
Scientists say one possible solution – though not an immediate solution – is to develop versions of the new therapies that are easier to administer. Altshuler said Vertex is trying to find ways to provide the same benefits without requiring chemo, which comes with serious risks like infertility. His team is working on making a pill that would not rearrange genes but would have the same goal: to help 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 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 will be as affordable as pills.
“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 pediatrics professor at Harvard Medical School, who is paid by the Howard Hughes Medical Institute. , which also supports the Associated. Department of Health and Science Press. Experts said governments are likely to play a key role in getting medicines to patients.
Dongre said he hopes gene therapy for sickle cell will eventually reach India. If he does, he wants his children to be among the first to receive it. Mazeze said she may wait to see how other patients have fared but will consider it for her son as well.
Both agreed that patients in every country – rich or poor – should have the choice.
“We are all part of one planet,” Dongre said.
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The Associated Press Health and Science Section is supported by the Howard Hughes Medical Institute Science and Media Education Group. The AP is solely responsible for all matters.
