In a call with 19 leaders of A.M.E. Zion church in North Carolina, Dr. Opeyemi Olabisi asked how many of them knew a friend.
The anguished replies came from the assembled pastors.
A childhood friend has died.
A father and sister died from the disease.
People lost.
Three cousins and a brother-in-law.
Dr. Olabisi had lost family members to the disease. The man who taught him to ride a bike in his native Nigeria died in his 30s.
Black Americans are disproportionately affected by the disease. Black people make up 12 percent of the U.S. population, but 35 percent of Americans have some kind of chronic disease. Black patients are more likely to contract the disease at a younger age.
There is a genetic factor that contributes to this burden. Many people with sub-Saharan ancestry have a copy of the APOL1 variant that puts them at high risk. APOL1 is one of the most powerful genes underlying a common human disease.
There is hope that the suffering can be alleviated. Several companies are working on drugs to target the APOL1 variant. Dr. Olabisi has a grant from the federal government to test whether baricitinib can help patients with the variant of arthritis.
There are difficult questions about the promise of treatments.
Should genetic testing be offered to anyone? The variant increase risk, but they do not preordain the disease. If someone knows that they have the variant, will they survive?
There are no proven ways to reduce the risk of having two copies of the variant. It can be difficult to control blood pressure in people with the variant.
The reason you can't get your blood pressure down is because you have a disease that raises your blood pressure.
Despite their joy at the progress being made, some experts like Dr. Olabisi say that policymakers should ignore the social and economic differences underlying the disease.
He said that they don't want to pretend that the biology doesn't exist.
It has been known for a long time that African Americans are five times more likely to suffer from kidney failure than whites.
Researchers were looking for a genetic cause. A decade ago, a team led by Giulio Genovese, Dr. David Friedman, and Dr. Martin Pollak found a variant of the APOL1 gene.
It was a complete surprise. Trypanosomes are part of the immune system and can cause illnesses. No one expected it to have anything to do with the kidneys.
The variant rose to a high level among people in Africa because of its ability to protect against African sleeping sickness, a disease caused by trypanosomes. It is similar to a gene variant that protects against Malaria but causes a disease in people who inherit two copies. In parts of Africa and other areas of the world where Malaria is common, the variant became prominent, but it is less common than the APOL1 risk variant.
A majority of Black Americans have at least one copy of the risk variant of the gene. People with two copies are more likely to get a disease that starts in young adulthood. Approximately 15 percent to 20 percent of people have two copies of the same disease.
In contrast, 7.7 percent of Americans with African ancestry have one copy of the variant.
What nature gave with one hand, it took away with the other, according to Dr. Olabisi.
One way to treat the disease is to block the genes from acting in the body. Researchers had to find out if APOL1 was needed. Drugs that blocked it might do more harm than good.
A farmer in India had no APOL1 gene. His kidneys were in good shape.
Too much is dangerous and too little is useless when it comes to drug development, according to Dr. Friedman. He said that the discovery of the farmer told him that he could probably drive the level of the APOL1 protein very low.
Some experts are not enthusiastic about the genetic discoveries.
Washington is a lecturer in ethics at Columbia University and author of the book "Medical Apartheid."
She said that the implication was that this is something happening in nature, so what can we do about it?
Joseph L. Graves, Jr., a professor of biological sciences at North Carolina Agricultural and Technical State University, raised another issue.
The environment in which people live determines the action of genetic variations. It is not how it works if you find a genetic variant and make the story simple. Environmental effects are important.
Structural racism and inequitable effects of law and policies can lead to a lack of access to health care for Black Americans.
While finding a treatment that might counteract the effect of the genetic variant is good news, she worried that social inequalities could not be fixed. Emphasizing the variant, she said, "deflects from our social responsibility to actually change the conditions that contribute to the onset of chronic kidney disease."
Twins Martin and Malcolm Lewis have a disease that can cause organ damage. When Martin was 10, his doctors said he had a disease called lupus.
In July 2020, Martin, an actor who lives in Brooklyn, was visiting Malcolm, a data analyst who was hospitalized at Duke with a flare-up. The brothers were told about APOL1 by Dr. Olabisi.
They talked about his research project, which involves testing Black Americans and people with a variant of the arthritis drug in a study. He asked if they wanted to know if they had APOL1 variant.
Malcolm said he was all for it. So was Martin.
When they were tested, the brothers found out they had the variant and that it was most likely damaging their kidneys. They didn't know how to react.
Malcolm said he was still trying to grapple with it.
But Dr. Olabisi was not surprised. When there is a secondary factor, researchers think the variant causes the disease. The body's own antiviral response, interferon, is produced in abundance in people with the disease.
People with Covid-19 can suffer a catastrophic collapse of their kidneys if they have the variant. Some viral infections that may go undetected can cause a surge of interferon that can set off the APOL1 variant. Interferon was tested as a treatment for Covid patients who had cancer.
Malcolm and Martin can't do much except take their medication.
Martin is glad he learned he has the variant. He knows what he's facing now.
He said that he is the kind of person who likes to plan.
While Dr. Olabisi waits for his study to start, a drug company is doing its own research. It was not clear what a drug was supposed to block because there wasn't an agreement on how APOL1 caused the disease.
If you don't understand the mechanism, you can't measure the effects in a lab.
It was known that the APOL1Protein protected against sleeping sickness by punching holes in the disease-causing trypanosomes.
Researchers at Vertex theorize that the variant spurred APOL1 to punch holes in other parts of the body.
Years of research in lab studies and in animals given genes for human APOL1 variants led to the discovery of a million compounds that might block APOL1.
The drug worked in animal models.
The drug was tested in a group of patients. The drug reduced the amount ofprotein in their urine.
In late March, the company announced it would take the next step, a clinical trial that would enroll approximately 66 patients in the first phase, to find the best dose, and 400 in the next phase, to see if the drug could improve kidney functions in patients with the risk.
Other companies have not revealed much about their plans. It was only in the early stages of testing a drug that could bind to APOL1, the messenger that carries instructions from the genes to the cells.
A co-founder and board member of the company said that the company is pursuing a strategy similar to the one of Vertex.
Dr. Kathiresan said he was optimistic this could move quickly.
At the meeting with the pastors in North Carolina, Dr. Olabisi said he wanted to test 5,000 Black people for the disease with a simple urine test and saliva test. The arthritis drug would be tested.
The pastor of Trinity A.M.E. Zion Church said that he was in.
They were enthusiastic. The effort would be led by people in the community and promoted on social media. People could be tested in their homes or in churches. It was a way to advance the day when a treatment would be available.
Dr. Olabisi smiled.
He said that it gave him energy and a lot of hope.
All Rights Reserved © 2024
