Advances in the Treatment of Childhood Diseases

Respiratory Distress Syndrome
Tyrosinemia
Primary IGF-1 Deficiency

Respiratory Distress Syndrome

Premature babies face an uphill battle as their fragile, still-developing systems fight to overcome many issues—including immature lungs struggling just to breathe. Respiratory distress syndrome (RDS) is caused by an infant's lack of surfactant, a natural lung-wetting agent, which normally develops between the 26^th and 34^th week of pregnancy. Without surfactant, the lungs cannot inflate.¹ Its absence in premature infants causes breathing difficulties and collapsed lungs. Prompt treatment is required for high-risk and premature infants. This treatment may include medicines, supplemental oxygen, and use of a ventilator.²

RDS is a common lung disorder in premature infants, affecting 10 of every 100 babies born prematurely in the United States, and nearly all babies born before 28 weeks of pregnancy. RDS usually occurs within the first 24 hours after birth.³

The discovery and approval of three new medicines for this one rare condition marked an important advance in the way that neonates with immature lungs are treated. With these medicines, premature infants have a better chance of surviving this life-threatening disorder.

PHARMACEUTICAL ADVANCES
Rescuing the Tiniest Lungs
Calfactant, approved in 1998, is used to treat babies with RDS, and also to prevent premature babies from developing RDS.⁴ A natural bovine-derived surfactant, calfactant attaches rapidly to the surface of the air-to-liquid interface within the lung's air sacs and modifies surface tension similarly to natural lung surfactant, thereby allowing the air sacs to expand and improving newborns' breathing ability.

Nitric oxide, approved in 1999, reduces the common complications of lung hypertension in newborns by expanding blood vessels in the lungs.⁵ Nitric oxide reduces the need for ventilator support and helps regulate the muscle tone in the arteries of the lungs.

Poractant alfa, approved in 1999, treats RDS in premature babies by reducing the amount of air trapped in the lining of the lungs. A natural porcine-derived surfactant, poractant alfa increases lubrication within the lung's air sacs thus improving expansion and ventilation.⁶

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Tyrosinemia

Children with the genetic, metabolic disorder tyrosinemia gradually develop liver failure and liver cancer, but the drug nitisinone, approved in 2002, can extend their lives. These children lack the enzyme that breaks down the amino acid tyrosine. Normally, the liver is where tyrosine is broken down; when it accumulates in the blood, it can lead to progressive liver failure and, often, cancer. Tyrosinemia may also cause damage to the kidneys, eyes, skin, and nervous system.

The most common and severe form of the disease is acute tyrosinemia, with which children are born or develop soon after birth. Infants with acute tyrosinemia exhibit rapid onset of symptoms, and they often fail to gain weight and grow. Infants with the less prevalent chronic tyrosinemia have a more gradual and less severe onset of symptoms.

Children who experience liver failure or are diagnosed with liver cancer as a result of tyrosinemia rarely make it into their twenties without a liver transplant. According to the FDA, this disorder affects 2,500 children in the United States.⁷

PHARMACEUTICAL ADVANCES
Patients' Pathway to Longer Life
Nitisinone opens the door to an extended lifespan for children with tyrosinemia. It decreases the level of tyrosine in the blood, thereby reducing the likelihood of liver failure and liver cancer. In combination with a diet restricted in the amino acids tyrosine and phenylalanine, this drug has been shown to increase the four-year survival rate of children who were diagnosed at less than two months of age to 88 percent. Historical data for children treated with dietary restrictions alone shows a survival rate of 29 percent for the same time period.⁸

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Primary IGF-1 Deficiency

Kids labeled as having "short stature" are signifcantly shorter than other children their same age and gender. Short stature can be caused by several factors, including family genetics, hormone problems, or various medical conditions.⁹

In recent years, it was found that short stature can also be the result of low insulin-like growth factor-1 (IGF-1) levels. This condition is called Primary IGF-1 Deficiency (Primary IGFD).¹⁰

PHARMACEUTICAL ADVANCES
First Medicine to Treat Primary IGFD
In 2005, the FDA approved mecasermin, the first treatment for approximately 6,000 children in the United States with severe Primary IGFD.¹¹ Mecasermin is a manufactured protein that functions like the natural human protein as a growth catalyst. This protein must be present for children's bones, cartilage, and organs to grow properly. An eight-year clinical trial demonstrated that, on average, children grew one inch per year for each year of therapy using this new medicine.¹²

Endnotes:

 ¹National Heart Lung and Blood Institute, What Causes Respiratory Distress Syndrome?, http://www.nhlbi.nih.gov/health/dci/Diseases/rds/rds_causes.html (accessed 1 October 2010).
 ²National Library of Medicine, MedlinePlus Medical Encyclopedia, Respiratory Distress Syndrome in Infants, http://www.nlm.nih.gov/medlineplus/ency/article/001563.htm (accessed 1 October 2010).
 ³National Heart Lung and Blood Instiute, What Is Respiratory Distress Syndrome?, http://www.nhlbi.nih.gov/health/dci/Diseases/rds/rds_whatis.html (accessed 1 October 2010).
 ⁴Food and Drug Administration, Infasurf (calfactant) Drug Approval Package, 25 http://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20521_Infasurf.cfm (accessed 1 October 2010).
 ⁵S. Reents et al., Clinical Pharmacology, Gold Standard, An Elsevier Company, Nitric Oxide, https://www.clinicalpharmacology.com/forms/login.aspx  (accessed 3 August 2005).
 ⁶S. Reents et al., Clinical Pharmacology, Gold Standard, An Elsevier Company, Poractant Alfa, https://www.clinicalpharmacology.com/forms/login.aspx (accessed 3 August 2005).
 ⁷Rare Disease Therapeutics, Inc., "FDA Approves Drug to Treat Rare Pediatric Liver Disease," 22 January 2002, http://www.raretx.com/january2002.html (accessed 3 October 2005).
 ⁸Ibid. 
 ⁹National Library of Medicine, MedlinePlus Medical Encyclopedia, Short Stature, http://www.nlm.nih.gov/medlineplus/ency/article/003271.htm (accessed 1 October 2010).
 ¹⁰Ipsen, IGF-1 is an Important Factor in the Growth of Children, Increlex.com, http://www.drugs.com/increlex.html (accessed 1 October 2010).
 ¹¹M. Herper, "FDA Approves Tercica's Increlex," Forbes.com, 31 August 2005, http://www.forbes.com/markets/2005/08/31/fda-increlex-tercica-0830markets01.html?partner=yahootix (accessed 1 October 2010).
 ¹²Drugs.com, Increlex, Drugs.com, http://www.drugs.com/increlex.html (accessed 1 October 2010).
 ¹³Food and Drug Administration, "Office of Orphan Products Development," Budget 2006, http://www.fda.gov/oc/oms/ofm/budget/2006/PDFs/Summary/Pages194thru199.pdf (accessed 7 September 2005).