Due to federal regulations, access to abortion medications is restricted, despite their record of safety and efficacy.
A few days before Christmas 2015, Paige Alexandria, a 28-year-old counselor at the Austin Women's Health Center in Texas, found out she was pregnant.
Alexandria had missed the cutoff for a medication abortion by three days.
"It was an unplanned pregnancy, and instantaneously I knew I needed an abortion," Alexandria recalls. Already a mother of two children, one with special needs, a third child was not something Alexandria and her husband felt prepared to take on. "Mentally, I knew my limit. I wasn't prepared for a third and I didn't want one," she says.
At an ultrasound appointment one week later, scans showed she was a little over eight weeks pregnant. Alexandria opted to have an abortion as soon as possible, and preferably with medication. "I really wanted to avoid a surgical abortion," she says. "It sounded a lot more invasive, and I'm already uncomfortable with pap smears and pelvic exams, so I initially went in wanting to do the pill."
But at the time, medication guidelines stipulated that one of the pills, called Mifepristone, could only be prescribed to end a pregnancy at eight weeks gestation or earlier – Alexandria had missed the cutoff by three days. If she wanted to end the pregnancy, she would need to undergo a surgical abortion, otherwise known as a vacuum aspiration abortion.
With a vacuum aspiration abortion, doctors dilate the cervix and manually aspirate out the contents of the uterus. Medication abortion, on the other hand, consists of the patient taking two pills – Mifepristone, which blocks the hormones that help the pregnancy develop, and Misoprostol, which empties the uterus over a period of days, identical to a miscarriage.
Alexandria was upset about the change of plans but resolute in her decision to end the pregnancy. "The fact that I didn't really have a choice in how my procedure was performed has made the experience just a little more sensitive for me," she says. She scheduled the earliest available appointment for a surgical abortion.
Paige Alexandria would have chosen to terminate her pregnancy with medication if the regulations were less stringent.
(Photo courtesy of Alexandria)
Like Alexandria, many people looking to terminate a pregnancy opt to do so with medication. According to research from the Guttmacher Institute, medication abortions accounted for nearly 40 percent of all abortions in the year 2017 – a marked increase from 2001, when medication abortions only accounted for roughly five percent of terminations. Taken 24-48 hours apart, Mifepristone and Misoprostol have a 95-99 percent success rate in terminating pregnancies up to 63 days – or nine weeks – of gestation, according to the American College of Obstetrics and Gynecology (ACOG).
But even though the World Health Organization (WHO) considers medical abortion to be highly safe and effective, the medication is still carefully guarded in the United States: Mifepristone is only available for terminating pregnancies up to 10 weeks gestation, per the FDA, even though limited research suggests that both are safe and effective at terminating pregnancies between 12 and 20 weeks.
Additionally, a separate set of regulations known as a Risk Evaluation and Mitigation Strategy (REMS) means that patients can only take Mifepristone under specific circumstances. Mifepristone must be distributed in person by a healthcare provider – usually interpreted in most states as a doctor or nurse practitioner – who has registered with the drug's manufacturer. The medication cannot be distributed through a pharmacy, so doctors who wish to provide the drug must stock the medication in-office, and both the provider and the patient must sign a form that warns them of the "risk of serious complications associated with Mifepristone," according to the FDA.
"REMS is a set of restrictions that the FDA puts on the distribution of drugs it considers dangerous or risky in some way," says Dr. Elizabeth Raymond, an OB-GYN and senior medical associate at Gynuity Health Projects. Although not always called REMS, these restrictions have been imposed on Mifepristone since the medication was approved by the FDA in 2000, Raymond says.
Raymond is part of a growing number of physicians and researchers who want to eliminate the REMS requirements for Mifepristone, also known by its brand name Mifeprex. In 2017, Raymond and several other physicians authored a paper in the New England Journal of Medicine (NEJM) arguing that Mifepristone is extremely safe and needlessly over-regulated.
"When the FDA first approved [Mifepristone] and imposed these requirements, they might have made sense 19 years ago when there was limited information about the use of this treatment in the United States," says Dr. Daniel Grossman, director at Advancing New Standards in Reproductive Health at UCSF and co-author of the 2017 report in the NEJM. "Now, after 19 years, it's clear that this medication is very safe, and safer than a lot of others available in a pharmacy."
Since 2000, Mifepristone has been implicated in 19 deaths, making its mortality rate 0.00063 percent.
According to their research, over three million people have taken Mifepristone since it was approved in 2000. Since then, Mifepristone has been implicated in 19 deaths, making its mortality rate 0.00063 percent. Even then, the risk is inflated, Grossman says.
"The requirement is that practitioners need to report any deaths that occur after taking these medications, and so you'll see deaths included in that figure which are homicides or suicides or something unrelated to taking Mifepristone," says Grossman. In contrast, Acetaminophen – better known as Tylenol – was associated with 458 overdose deaths between 1990 and 1998, as well as 56,000 emergency room visits and 26,000 hospitalizations. Sildenafil, better known as Viagra, was linked to 762 deaths in the first twenty months after it was approved by the FDA. Yet neither Tylenol nor Viagra have been burdened with the same REMS restrictions as Mifepristone.
"It's clearly about more than just the safety of the medication at this point," says Grossman. "It's more about stigma related to abortion and politics."
For people who want a medication abortion, the REMS requirements mean they often need to take off work to schedule a doctor's appointment, arrange for transportation and childcare, and then arrange an additional doctor's appointment days afterward to take the second dose of medication. While surgical abortion procedures are quicker (usually a one-day outpatient procedure, depending on gestation), many people prefer having the abortion in the comfort of their home or surrounded by family instead.
Paige Alexandria, who counsels people seeking abortions at her job, says that survivors of sexual violence often prefer medical abortions to surgical ones. "A lot of time survivors have a trauma associated with medical instruments or having pelvic exams, and so they're more comfortable taking a pill," she says.
But REMS also creates a barrier for healthcare providers, Grossman says. Stocking the medication in-office is "a hassle" and "expensive," while others are reluctant to register their name with the drug manufacturer, fearing harassment or violence from anti-choice protestors. As a result, the number of practitioners willing to provide medical abortions nationwide is severely limited. According to Grossman's own research published in the journal Obstetrics and Gynecology, 28 percent of OBGYNs admitted they would administer medication abortions if it were possible to write a prescription for Mifepristone rather than stock it in-office.
Amazingly, the restrictions on Mifepristone have loosened since it first came on the market. In 2016, the FDA updated the guidelines on Mifepristone to allow its use until 10 weeks gestation, up from eight weeks. But doctors say the REMS restrictions should be eliminated completely so that people can obtain abortions as early as possible.
"REMS restrictions inhibit people from being able to get a timely abortion," says Raymond, who stresses that abortion is generally more comfortable, more affordable, and safer for women the earlier it's done. "Abortion is very safe no matter when you get it, but it's also easier because there's less risk for bleeding, infections, or other complications," Raymond says. Abortions that occur earlier than eight weeks of gestation have a complication rate of less than one percent, while an abortion done at 12 or 13 weeks has a three to six percent chance of complications.
And even for people who want a medication abortion early on in their pregnancy, REMS restrictions make it so that they may not have time to obtain it before the 10-week period lapses, Raymond says.
"If you're seven weeks pregnant but it takes you three weeks to figure out travel and childcare arrangements to go into the doctor and take this medication, now you're at the cutoff date," she says. "Even if you manage to get an abortion at nine weeks, that's still a later gestational age, and so the risks are increased."
In 2016, at a little over nine weeks gestation, Alexandria completed her abortion by having a D&E. But because she didn't have anyone to drive her home after the procedure, she wasn't able to have sedation throughout, something she describes as "traumatic."
"I had the abortion completely aware and coherent, and paired with the fact that I hadn't even wanted a surgical abortion in the first place made it harder to deal with," Alexandria says.
"When you're just a day or two past eight weeks and you want an abortion – why is medication not immediately available?"
Today, Alexandria shares her story publicly to advocate for abortion care. Although she doesn't regret her surgical abortion and acknowledges that not everyone experiences surgical abortion the same way she did, she does wish that she could have gone a different route.
"If I had to do it over, I would still try to do the pill, because [the surgical abortion] was such a terrifying experience," she says. "When you're just a day or two past eight weeks and you want an abortion – why is medication not immediately available? It just doesn't make sense."
In a recent research trial, patients with Parkinson's disease reported that their symptoms had improved after stem cells were implanted into their brains. Martin Taylor, far right, was diagnosed at age 32.
For years, there's been little improvement in the standard treatment. Patients are typically given the drug levodopa, a chemical that's absorbed by the brain’s nerve cells, or neurons, and converted into dopamine. This drug addresses the symptoms but has no impact on the course of the disease as patients continue to lose dopamine producing neurons. Eventually, the treatment stops working effectively.
BlueRock Therapeutics, a cell therapy company based in Massachusetts, is taking a different approach by focusing on the use of stem cells, which can divide into and generate new specialized cells. The company makes the dopamine-producing cells that patients have lost and inserts these cells into patients' brains. “We have a disease with a high unmet need,” says Ahmed Enayetallah, the senior vice president and head of development at BlueRock. “We know [which] cells…are lost to the disease, and we can make them. So it really came together to use stem cells in Parkinson's.”
In a phase 1 research trial announced late last month, patients reported that their symptoms had improved after a year of treatment. Brain scans also showed an increased number of neurons generating dopamine in patients’ brains.
Increases in dopamine signals
The recent phase 1 trial focused on deploying BlueRock’s cell therapy, called bemdaneprocel, to treat 12 patients suffering from Parkinson’s. The team developed the new nerve cells and implanted them into specific locations on each side of the patient's brain through two small holes in the skull made by a neurosurgeon. “We implant cells into the places in the brain where we think they have the potential to reform the neural networks that are lost to Parkinson's disease,” Enayetallah says. The goal is to restore motor function to patients over the long-term.
Five patients were given a relatively low dose of cells while seven got higher doses. Specialized brain scans showed evidence that the transplanted cells had survived, increasing the overall number of dopamine producing cells. The team compared the baseline number of these cells before surgery to the levels one year later. “The scans tell us there is evidence of increased dopamine signals in the part of the brain affected by Parkinson's,” Enayetallah says. “Normally you’d expect the signal to go down in untreated Parkinson’s patients.”
"I think it has a real chance to reverse motor symptoms, essentially replacing a missing part," says Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh.
The team also asked patients to use a specific type of home diary to log the times when symptoms were well controlled and when they prevented normal activity. After a year of treatment, patients taking the higher dose reported symptoms were under control for an average of 2.16 hours per day above their baselines. At the smaller dose, these improvements were significantly lower, 0.72 hours per day. The higher-dose patients reported a corresponding decrease in the amount of time when symptoms were uncontrolled, by an average of 1.91 hours, compared to 0.75 hours for the lower dose. The trial was safe, and patients tolerated the year of immunosuppression needed to make sure their bodies could handle the foreign cells.
Claire Bale, the associate director of research at Parkinson's U.K., sees the promise of BlueRock's approach, while noting the need for more research on a possible placebo effect. The trial participants knew they were getting the active treatment, and placebo effects are known to be a potential factor in Parkinson’s research. Even so, “The results indicate that this therapy produces improvements in symptoms for Parkinson's, which is very encouraging,” Bale says.
Tilo Kunath, a professor of regenerative neurobiology at the University of Edinburgh, also finds the results intriguing. “I think it's excellent,” he says. “I think it has a real chance to reverse motor symptoms, essentially replacing a missing part.” However, it could take time for this therapy to become widely available, Kunath says, and patients in the late stages of the disease may not benefit as much. “Data from cell transplantation with fetal tissue in the 1980s and 90s show that cells did not survive well and release dopamine in these [late-stage] patients.”
Searching for the right approach
There's a long history of using cell therapy as a treatment for Parkinson's. About four decades ago, scientists at the University of Lund in Sweden developed a method in which they transferred parts of fetal brain tissue to patients with Parkinson's so that their nerve cells would produce dopamine. Many benefited, and some were able to stop their medication. However, the use of fetal tissue was highly controversial at that time, and the tissues were difficult to obtain. Later trials in the U.S. showed that people benefited only if a significant amount of the tissue was used, and several patients experienced side effects. Eventually, the work lost momentum.
“Like many in the community, I'm aware of the long history of cell therapy,” says Taylor, the patient living with Parkinson's. “They've long had that cure over the horizon.”
In 2000, Lorenz Studer led a team at the Memorial Sloan Kettering Centre, in New York, to find the chemical signals needed to get stem cells to differentiate into cells that release dopamine. Back then, the team managed to make cells that produced some dopamine, but they led to only limited improvements in animals. About a decade later, in 2011, Studer and his team found the specific signals needed to guide embryonic cells to become the right kind of dopamine producing cells. Their experiments in mice, rats and monkeys showed that their implanted cells had a significant impact, restoring lost movement.
Studer then co-founded BlueRock Therapeutics in 2016. Forming the most effective stem cells has been one of the biggest challenges, says Enayetallah, the BlueRock VP. “It's taken a lot of effort and investment to manufacture and make the cells at the right scale under the right conditions.” The team is now using cells that were first isolated in 1998 at the University of Wisconsin, a major advantage because they’re available in a virtually unlimited supply.
Other efforts underway
In the past several years, University of Lund researchers have begun to collaborate with the University of Cambridge on a project to use embryonic stem cells, similar to BlueRock’s approach. They began clinical trials this year.
A company in Japan called Sumitomo is using a different strategy; instead of stem cells from embryos, they’re reprogramming adults' blood or skin cells into induced pluripotent stem cells - meaning they can turn into any cell type - and then directing them into dopamine producing neurons. Although Sumitomo started clinical trials earlier than BlueRock, they haven’t yet revealed any results.
“It's a rapidly evolving field,” says Emma Lane, a pharmacologist at the University of Cardiff who researches clinical interventions for Parkinson’s. “But BlueRock’s trial is the first full phase 1 trial to report such positive findings with stem cell based therapies.” The company’s upcoming phase 2 research will be critical to show how effectively the therapy can improve disease symptoms, she added.
The cure over the horizon
BlueRock will continue to look at data from patients in the phase 1 trial to monitor the treatment’s effects over a two-year period. Meanwhile, the team is planning the phase 2 trial with more participants, including a placebo group.
For patients with Parkinson’s like Martin Taylor, the therapy offers some hope, though Taylor recognizes that more research is needed.
BlueRock Therapeutics
“Like many in the community, I'm aware of the long history of cell therapy,” he says. “They've long had that cure over the horizon.” His expectations are somewhat guarded, he says, but, “it's certainly positive to see…movement in the field again.”
"If we can demonstrate what we’re seeing today in a more robust study, that would be great,” Enayetallah says. “At the end of the day, we want to address that unmet need in a field that's been waiting for a long time.”
Editor's note: The company featured in this piece, BlueRock Therapeutics, is a portfolio company of Leaps by Bayer, which is a sponsor of Leaps.org. BlueRock was acquired by Bayer Pharmaceuticals in 2019. Leaps by Bayer and other sponsors have never exerted influence over Leaps.org content or contributors.