Researcher offers her hope for release from lifelong pain

For as long as she can remember, Summer Harris has been in pain. Sometimes dull, throbbing pain, but often pain so piercing that she feels "like somebody is stabbing me in the back and legs, my head, my knees." It can last for hours or linger on for days.

 

Sickle cell disease, a genetic ailment that makes her bone marrow produce distorted, oxygen-starved red blood cells shaped like crescents or sickles, has kept the North Inglewood woman on the sidelines of life throughout her 24 years — out of the school she loved, in the hospital countless times, away from her four brothers and sisters and close friends.

           

The pain can recur anytime the sickle cells start to clog her small blood vessels and keep her body from getting the oxygen it needs. In addition to pain that Harris calls "indescribable," it can also cause strokes. Harris has had two so far, one at age 6 and another at age 20. Strokes have affected her brain. "My learning skills aren't the same," said Harris, who had to leave school in the seventh grade when she started having seizures. She is currently on five pain medications and was recently released after a month's stay at a hospital. "I loved school and being with my classmates," she said. But the strokes have left her reading at the fourth-grade level.

 

The general public has little understanding about how devastating this disease can be, said Dr. Donald Kohn, a renowned professor of microbiology, immunology and molecular genetics as well as pediatrics who was recruited to UCLA in February.

 

Sickle cell affects roughly one in 500 African Americans and about one in 1,000 to 1,400 Latinos in the U.S. Although bone marrow transplants help when a donor can be found who's a perfect match, the shortened lifespan of sickle cell patients — they live on average into their 40s —  has not been lengthened appreciably by these conventional therapies.

 

But that may change because of a $9.2 million grant Kohn is receiving from the California Institute for Regenerative Medicine, the state's stem cell agency. On Oct. 28, the institute announced grants totaling more than $250 million that are going to 14 disease teams.

 

UCLA scientists will receive three such grants for a total of $49.2 million to turn leading-edge stem cell science into stem cell therapies for sickle cell, HIV/AIDS and brain, ovarian and colorectal cancers. That brings the total amount of state funding awarded to scientists with the Broad Stem Cell Research Center at UCLA to nearly $122 million since 2005. Other Broad center scientists are collaborators in disease team projects based at other research institutions. Dr. Hanna Mikkola will work with a team seeking better treatments for leukemia, while Drs. Paul Mischel, Tim Cloughesy and Linda Liau will collaborate with a team focusing on glioblastoma. In addition, Dr. S. Thomas Carmichael, associate professor in the UCLA Department of Neurology, will serve as co-principal investigator for a team developing a new treatment for stroke.

 

In his research, Kohn will use an approach developed by another lab that made a virus to carry a gene into the stem cells, Kohn and his team will transplant sickle cell patients with their own bone marrow after their adult blood stem cells are genetically corrected by adding a hemoglobin gene that blocks the sickling of red blood cells.

 

"If we could take their own bone marrow cell and put into it a gene to fix the sickle cells, we could use self-transplantation of their own gene-corrected bone marrow stem cells," Kohn said.

 

The gene that Kohn will use comes from fetal hemoglobin, which is different from the hemoglobin adults produce, richer in oxygen. The gene usually turns off at birth. But for a few people, the gene stays on. Scientists have found that the fetal hemoglobin gene prevents the sickling of red blood cells. 

 

Under the terms of the grant, Kohn will have four years to reach the clinical trial stage with his stem cell therapy. The grant will fund all the steps it will take for him to get to clinical trials — the lab work, the development of protocols and all the regulatory reviews.  If this is successful, he said, "there's a whole group of genetic blood cell diseases that can be treated with bone marrow self-transplants." He has already started a clinical trial that uses stem cell therapy to treat severe combined immunodeficiency (SCID), sometimes known as "bubble boy disease," named after a boy with SCID who lived for 12 years in a plastic, germ-free bubble.  

 

Kohn's grant and the timeframe it sets for clinical trials have given Harris hope that she may one day be free of pain and able to live a normal life. "I would be so happy — not just for me, but for all the sickle cell people who will have a chance to experience a normal life," she said.

 

To read more about the grants, see this.