Fetal Stem Cell Therapy Trial for Brittle Bone Disease

Dr. Cecilia Gӧtherström works as a medical researcher at the Karolinska Institutet in Stockholm, Sweden. Earlier this month, Dr Gӧtherström announced the commencement of the first clinical trial that utilizes fetal stem cell transplants to treat the brittle bone disease, Osteogenesis Imperfecta.

Osteogenesis imperfect (OI) was made famous by the Bruce Willis/Samuel Jackson movie “Unbreakable.” In this movie, Samuel Jackson played a wheel-chair bound savant whose bones were incredibly fragile, but acted as a mentor to Bruce Willis’ character who had a tendency to not become injured despite being in accidents and other traumatic events. Willis becomes a kind of local protector of the weak and innocent in his community under Jackson’s tutelage. I will not give away the surprising ending, but the fact that Jackson’s character had OI and his bones broke so easily put OI in the public’s consciousness.

OI is actually a group of genetic disorders that affects an estimated 6 to 7 per 100,000 people worldwide and prevents the bones from forming properly. This disease results from mutations in the COL1A1, COL1A2, CRTAP, and P3H1 genes. More than 90 percent of all cases of OI result from mutations in the COL1A1 and COL1A2 genes. The COL1A1 and COL1A2 genes encode the type I collagen proteins. Collagen is the most abundant protein in bone, skin, and other connective tissues. Patients with OI have fragile bones that break easily, sometimes with no apparent cause. OI can also cause loose joints, fatigue, early hearing loss, and respiratory problems. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person’s lifetime.

The publication SelectScience interviewed Dr. Gӧtherström who is the coordinator of this clinical trial that will use stem cell therapy to treat babies diagnosed with OI before they are ever born. Dr Gӧtherström told SelectScience that she and her colleagues selected OI as a disease to attack with stem cell treatment because “no good treatment exists.” Dr. Gӧtherström continued: “OI is a chronic disorder that affects the patient throughout their lifetime with reduced quality of life.” Also, because OI causes poor bone mineralization, fractures and malformation of the bones commences by the time the baby is born. Therefore, physicians can diagnose OI during pregnancy, and once it has been diagnosed, it is crucial to initiate treatment as soon as possible.

Dr. Gӧtherström and her colleagues will infuse stem cells into the fetal bodies of babies afflicted with OI by employing the same protocol that is generally used for blood transfusions during pregnancy. This is a very well-tested technique that carries a very little risk to the mother and her baby. According to Dr. Gӧtherström, there is a theoretical risk of the donor cells acquiring mutations that causing cancer in the mother, but this is very unlikely.

Fetal stem cell therapy has some benefits over other types of stem cell therapy. According to Dr. Gӧtherström, “Fetuses do not have a fully developed immune system, so the donor cells may have a better engraftment potential.” Also, fetal Mesenchymal Stem Cells (MSC) have a far better ability to form bone tissue than adult stem cells.

“If this proves to be safe and efficient, we will explore other disorders that can be treated prenatally, such as other skeletal dysplasias, or metabolic disorders,” Dr Gӧtherström explained. The success of this trial could open up new avenues for prenatal therapies to become more common. Dr. Gӧtherström believes that prenatal diagnosis of similar chronic disorders will shift, from delaying or slowing down the onset of a condition to actually treating it.

Stem Cells Treat Babies With Brittle Bone Disease While Still in the Womb

A new study published by the journal STEM CELLS Translational Medicine shows that stem cells can be effective in treating brittle bone disease, a debilitating and sometimes lethal genetic disorder.

Also known as osteogenesis imperfecta (OI), this genetic disorder was popularized by actor Samuel T. Jackson in the Bruce Willis movie “Unbreakable.” OI is characterized by fragile bones that cause patients to suffer hundreds of fractures over the course of a lifetime. According to the OI Foundation, other symptoms include muscle weakness, hearing loss, fatigue, joint laxity, curved bones, scoliosis, brittle teeth and short stature. In the more severe cases of OI, restrictive pulmonary disease also occurs. Unfortunately, to date no cure exists for OI.

Physicians use ultrasound to detect OI in babies before they are born. In this study, an international research team treated two patients for the disease with mesenchymal stem cells (MSCs) while the infants were still in the womb. After they were born, the babies were given additional mesenchymal stem cell treatments.

“We had previously reported on the prenatal transplantation for the patient with OI type III, which is the most severe form in children who survive the neonatal period,”said Cecilia Götherström, Ph.D., of the Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. She and Jerry Chan, M.D., Ph.D., of the Yong Loo Lin School of Medicine and National University of Singapore, and KK Women’s and Children’s Hospital, led the study that also included colleagues from the United States, Canada, Taiwan and Australia.

“The first eight years after the prenatal transplant, our patient did well and grew at an acceptable rate. However, she then began to experience multiple complications, including fractures, scoliosis and reduction in growth, so the decision was made to give her another MSC infusion. In the two years since, she has not suffered any more fractures and improved her growth. She was even able to start dance classes, increase her participation in gymnastics at school and play modified indoor hockey,”Dr. Götherström added.

The second child suffered from a milder form of OI and received a stem cell transfusion 31 weeks into gestation and did not suffer any new fractures for the remainder of the pregnancy or during infancy. She followed her normal growth pattern — just under the third percentile in height, but when she was 13 months old, she stopped growing. Six months later, the doctors gave her another infusion of stem cells and she resumed growing at her previous rate.

“Our findings suggest that prenatal transplantation of autologous stem cells in OI appears safe and is of likely clinical benefit and that re-transplantation with same-donor cells is feasible. However, the limited experience to date means that it is not possible to be conclusive, for which further studies are required,”Dr. Chan said.

“Although the findings are preliminary, this report is encouraging in suggesting that prenatal transplantation may be a safe and effective treatment for this condition,”said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.