“I was all for it,” said Malcolm. So is Martin.
When tested, the brothers found that they had the variants and that the variants, not lupus, most likely damaged their kidneys. They hardly knew how to react.
“I’m still trying to struggle with it,” Malcolm said.
But Dr. Olabisi was not surprised. Researchers believe that the variants only cause kidney disease if there is a secondary factor. A key candidate is the body’s own antiviral response, interferon, which is produced in abundance in people with lupus.
High levels of interferon also occur in people with untreated HIV. As with people with Covid-19, if they have the variants, they can have an unusual and catastrophic kidney failure. Other viral infections, including some that go undetected, can cause an increase in interferon that could cause the APOL1 variants. Interferon is also used as a drug to treat some diseases, including cancer, and has been tested as a treatment for Covid patients.
For now, Malcolm and Martin can do little except take medication to control their lupus.
Martin said he understands all that, but he’s glad to hear he has the variants. Now he knows what to expect.
“I’m the kind of person who likes to plan,” he said. “It does make a difference.”
From a gene to drugs
While Dr. Olabisi is waiting to begin his studies, a pharmaceutical company, Vertex, has continued its own research. But there was no agreement on how APOL1 variants caused kidney disease, so it wasn’t clear what a drug was supposed to block.
“If you don’t understand the mechanism, that means you can’t measure effects in a lab,” says Dr. David Altshuler, Chief Scientific Officer at Vertex. “And if you can’t measure effects in the lab, you can’t correct them.”
It was known how the APOL1 protein protected against sleeping sickness – it punched holes in the disease-causing trypanosomes, causing them to swell with fluid and burst.
