What is in utero therapy?
Currently, treatments for genetic conditions are administered after birth when symptoms have already appeared. In utero therapies are unique because they treat babies before birth. Giving therapy prenatally allows the earliest chance to prevent, delay, or treat symptoms and reduce future complications from a condition. Importantly, in utero therapies may offer the possibility of a one-time curative treatment. Gene therapy, enzyme replacement therapy, and stem cell transplant are all examples of treatments with promising applications before birth.
What is gene therapy?
Genes contain the instructions for our bodies to produce proteins, the building blocks that are crucial for growth and development. Genetic conditions are caused by changes, or mutations, in these genes which can lead to health problems, birth defects, or developmental differences. Gene therapy is a technique that aims to prevent, stop, or potentially cure diseases caused by mutations. Gene therapy can involve replacing parts of a gene, introducing entirely new working copies of a gene, or even deactivating a gene that is causing disease. It has the potential to treat a wide range of conditions caused by genetic mutations that result in too little or too much protein production.
Gene therapy before birth has some key benefits over gene therapy after birth. A baby's immune system isn't fully formed yet while in the womb. This lowers the chance that the baby's body will reject gene therapy. It also means a smaller dose of gene therapy can work well or even better when given before birth.
What is enzyme replacement therapy?
Enzyme replacement therapy (ERT) is a treatment that replaces missing or defective enzymes in the body. Usually, ERT is given after birth and requires lifelong infusions which can be expensive and hard to manage. Researchers hope that in utero ERT can help babies with certain genetic conditions like lysosomal storage disorders to live longer and healthier lives.
Many severe and life-limiting genetic conditions do not have any therapy available. In utero ERT may be the first and only opportunity for an affected baby to receive life-altering treatment. The advantages of in utero therapy have been demonstrated in studies, including a baby girl affected with infantile-onset Pompe disease recently highlighted in a New England Journal of Medicine article. This lysosomal storage disorder is one of eight being treated with in utero ERT in an FDA-approved Phase 1 clinical trial.
What is in utero stem cell transplant?
Many people with certain blood disorders need a stem cell transplant (SCT) to cure their disease. In a stem cell transplant, a patient gets healthy stem cells from a donor. Stem cells make blood cells in the bone marrow. The new stem cells replace the patient's unhealthy blood cells over time. But stem cell transplants have risks, and it is difficult to find a donor who is a perfect match.
A baby's immune system works differently before birth making in utero stem cell transplants (IUSCT) potentially safer than those after birth. IUSCT removes the need for drugs to suppress the immune system that are often needed in traditional stem cell transplants performed after birth and overcomes the challenge of finding a perfect donor match.
Researchers at UCSF are studying stem cell transplants on babies in utero with a serious blood disease called alpha-thalassemia major (ATM). Often, these babies become very sick during a pregnancy and may not survive outside the womb, or rely on frequent blood transfusions for their entire lives. The goal of in utero stem cell transplants are to help affected babies to live longer and healthier lives. If proven safe and effective, IUSCT may become a potential curative treatment for many types of severe genetic blood disorders.
What does the future hold for in utero therapy?
While in utero therapies represent exciting new therapeutic strategies for many genetic conditions with limited or nonexistent treatment options, it also comes with a number of safety and ethical considerations. Extensive research is still needed to determine the long-term benefits, risks, and efficacy of these treatments. It will take collaboration between scientists, regulators, physicians, and most importantly, patients and families with these disorders to make this technology a reality.
If you or someone you know may be a candidate for a gene therapy clinical trial, you can visit www.clinicaltrials.gov to explore ongoing opportunities. A genetic counselor can help you determine your genetic risk and enroll in these trials. To find a certified genetic counselor near you, visit: https://findageneticcounselor.nsgc.org/
References
1 https://www.genome.gov/dna-day/15-ways/rare-genetic-diseases
2 Cohen, J. L., Chakraborty, P., Fung-Kee-Fung, K., Schwab, M. E., Bali, D., Young, S. P., Gelb, M. H., Khaledi, H., DiBattista, A., Smallshaw, S., Moretti, F., Wong, D., Lacroix, C., El Demellawy, D., Strickland, K. C., Lougheed, J., Moon-Grady, A., Lianoglou, B. R., Harmatz, P., Kishnani, P. S., … MacKenzie, T. C. (2022). In Utero Enzyme-Replacement Therapy for Infantile-Onset Pompe's Disease. The New England journal of medicine, 387(23), 2150–2158. https://doi.org/10.1056/NEJMoa2200587
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