Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV), or alveolar capillary dysplasia (ACD) for short, is a rare, congenital, and life-threatening disorder. Without receiving lung transplants in infancy, many children born with ACD live from only a few weeks to less than one year. But according to News Medical, a recent study used high-tech nanoparticles to treat pulmonary hypertension (high blood pressure that affects arteries in the lungs and heart) in mice models of ACD. If these findings could one day be replicated in humans, it could significantly improve patient outcomes. See the full findings published in Circulation.
Alveolar Capillary Dysplasia (ACD)
In most cases, alveolar capillary dysplasia (ACD), a rare genetic order, results from FOXF1 gene mutations. However, an estimated 10-20% of diagnoses are idiopathic (of unknown cause). Normally, FOXF1 encodes for transcription factors, proteins which play an important role in multiple bodily functions. But in patients with ACD/MPV, the lack of proteins prevents alveolar capillaries (small blood vessels in the lungs) from properly developing or from being situated correctly. As a result, patients experience pulmonary hypertension and inadequate oxygen distribution throughout the body. Infants with ACD may present, within a few days of birth, as short of breath and cyanotic. Altogether, around 200 cases of ACD have been documented globally. However, considering potential misdiagnosis, the accurate number is unknown.
Typically, ACD symptoms appear within a few minutes to days following birth. Unfortunately, this is a largely fatal condition without early lung transplantation. Symptoms include:
- Cyanosis (bluish discoloration of the skin, lips, and nails)
- Shortness of breath and/or difficulty breathing
- Pulmonary hypertension
- Abnormal twisting of the large intestine
- Note: Additional gastrointestinal defects may also be present.
- Hypoxia (low oxygen in the bloodstream)
- Urinary tract and kidney dysfunction
- Heart defects
Nanoparticles
During the study, researchers wanted to understand whether a new treatment approach – using high-tech nanoparticles – could improve pulmonary function in mice models of ACD/MPV. Researchers from Cincinnati Children’s and the University of Cincinnati first developed mice models of ACD/MPV. Without treatment, approximately 70% of these mice die within 28 days of birth.
Next, researchers treated these mice models using high-tech nanoparticles as carriers. This colloidal drug delivery system does not permanently change the body, as gene therapies might. Instead, the nanoparticles deliver STAT3 directly to the lungs. Since STAT3 is a key downstream target of FOXF1, delivering a functioning gene can help improve blood vessel growth and pulmonary function. Nanoparticles also offer a unique delivery system; they do not stay in the body for more than one week, offer low toxicity, and can provide sustained benefits. Even more excitingly, this particular nanoparticle treatment was developed by University of Cincinnati graduate students!
For example, within this study, mice models treated with just a singular injection saw:
- Improved survival rates
- Only 35% died within 28 days following treatment, as opposed to the original 70%. Thus, this injectable treatment halved mortality rates.
- Lower blood pressure
- Better alveolar capillary density
- Increased oxygenation
Altogether, this treatment helped prompt more normal lung development and prevent permanent pulmonary malformations. Although much more research is needed before any human trials can be held, these results are looking promising.
