Depression medicine: Breakthrough for sickle cell disease?
After more than three decades of studying life-threatening sickle cell disease, the most prevalent of all hereditary illnesses, University of Michigan Medical School researchers have discovered that an anti-depressant marketed since the 1960s wipes out the disorder in lab-tested human blood and mice.
If upcoming clinical trials prove it’s safe for adult sickle cell patients to ingest tranylcypromine, the anti-depressant could be an alternative to the current treatment — hydroxyurea — which is mainly a cancer fighter.
Hydroxyurea, which also is highly toxic, is only moderately effective on about half of sickle cell sufferers, most of whom are of African descent. The disorder, which causes blood cells to harden, become C-shaped, and ultimately clog arteries, also strikes people of Mediterranean, Middle Eastern and South Asian ancestry.
The genetic mutation that causes sickle cell disease was the first mutation of any inherited disease to be discovered, a finding made in 1949, also at the University of Michigan. That was a “fascinating” discovery, said molecular biologist and chemist James Douglas Engel, lead researcher in Michigan’s current sickle cell study, published last month in Nature Medicine.
“It prompted me,” Engel continued, “to believe that, ‘okay, here’s a disease we’re really going to be able to [soon] cure.’ It was with that idea that I began this work 35 years ago … It wasn’t until about 10 years ago that we figured out what a possible mechanism for controlling [the defect] might be.”
And two years ago, when the Michigan researchers zeroed in on a molecule involved in cell sickling, they began scouting a drug to combat that, said Engel, who directed the four-person research team and is co-director of the University of Michigan’s Center for Organogenesis. The center studies human organ development. Organ damage caused by the defective blood cells is a leading cause of premature death among those with sickle cell disease.
Clinical trials using the anti-depressant to treat adult sickle cell patients will take place at Wayne State University in Detroit. A pre-trial review required by the federal government is underway there; it will dictate when and with whom the clinical trials begin.
Worldwide, millions are believed to have sickle cell disease. In the United States, the federal Centers for Disease Control estimates that 100,000 African-Americans have it but cautions that the precise number of people with the illness is unknown. An estimated one out of 500 African-American babies and one in 36,000 Latino-American babies are born with sickle cell disease, according to the CDC; one in 12 blacks carry the sickle cell trait.
Though considered less hazardous than hydroxyurea, tranylcypromine — commonly called TCP — has its own side effects, ranging from anxiety to worsened depression to uncontrollable bodily shaking. Combined with certain foods — from charbroiled steaks to red wine — TCP is potentially deadly, Engel said.
Nevertheless, the prospect of treating sickle cell disease with TCP represents a promising breakthrough on a disease for which there has been insufficient scientific progress over the last 60 years and that remains misunderstood even by physicians, said Dr. Andrew Campbell, who has collaborated with Engel. Campbell is director the pediatric sickle cell program at the University of Michigan’s C.S. Mott Children’s Hospital.
“When I came to this area of work in the late 1990s, essentially what I saw was a lack of research … devoted to sickle cell. Number two, there’s often been a lack of compassion from physicians taking care of people with sickle cell,” Campbell said.
Clustering sickle cells cause excruciating pain, demand relatively frequent hospitalizations and the immediate attention of patients’ doctors, Campbell said.
“Especially in the adult world — even though patients are actually in a tremendous amount of pain — health care providers will brush them aside.”
In the face of that, some patients grow reluctant to seek palliative care. They’re often looked upon as akin to recreational drug addicts, Campbell added.
“It’s ‘Oh, you’re here again for pain medicine? You should go home. We just saw you.’”
It is a dismissal driven partly, Campbell said, by stereotypes of race and class.
More effective treatment of sickle cell will undo some of those wrong-headed presumptions, Campbell said. He lauds the Michigan researchers and is hopeful that the clinical trials will bear fruit.
About TCP, Engel adds: “This isn’t a perfectly proven therapy yet. We need to test it in humans. We need to find drugs other than TCP that work better, that are more effective at lower concentrations and have fewer side effects.”
New York-based freelancer Katti Gray specializes in reporting health, higher education and criminal justice. Her byline has appeared in The Washington Post, Salon, Reuters, Newsday, Ms., Essence, Ebony, CNN.com, ABCNews.com and other national and regional publications. Follow her on twitter@KattiGray.