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Breakthrough Drug for Progeria- rapid-aging disease of children

Breakthrough Drug for Progeria- rapid-aging disease of children

Hutchinson-Gilford Progeria is a very rare genetic condition occurring in just 1 in 4 million births.It is characterized by premature aging and is fatal by the late teens. But a new drug originally designed for a very different purpose may be changing the prognosis of disease in coming times.Until recently, there have been no known therapies for the disease and the natural history of progeria is death, usually due to cardiac causes or stroke.Lonafarnib a  farnesyl transferase inhibitor that has been found useful in hepatitis delta virus infection and is being investigated for its anti-cancer properties was investigated for its efficacy in Progeria.

Leslie B. Gordon, Heather Shappell, Joe Massaroet al conducted a study to evaluate the association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with the mortality rate in children with Hutchinson-Gilford progeria syndrome.The researchers found that patients with Hutchinson-Gilford progeria syndrome on monotherapy with Lonafarnib had a lower mortality rate as compared to no treatment.The Study has appeared in JAMA.

In this cohort study, the researchers included  27 treated patients with Hutchinson-Gilford progeria syndrome and compared them with a pool of 103 contemporaneous untreated patients.Treated patients received oral lonafarnib (150 mg/m2) twice daily. Untreated patients received no clinical trial medications.They found that treatment with lonafarnib monotherapy compared with no treatment was associated with a significantly lower mortality rate (3.7% vs 33.3%) after a median of 2.2 years of follow-up.

 The primary gene defect in progeria is in lamin A which normally gets farnesylated, but the farnesyl part of the protein is subsequently cleaved. In progeria, that cleavage site is rendered inactive, leading to retention of the farnesyl group and accumulation of the altered protein which leads to the progeria phenotype.Researchers wondered whether inhibiting farnesylation in the first place would make a difference and found that  Lonafarnib does just that.

The first trial of lonafarnib conducted on July 30, 2013, led to promising results when kids treated with the drug had improved weight gain and less skeletal rigidity. But only now was there enough data collected to look at all-cause mortality.

 This is a story that is inspiring on many levels. There’s obviously the potential to transform the lives of a group of very special children. But it’s also exemplary of the scientific method gone right — where rigorous basic science and the smart application of an existing drug combine to produce outcomes that are genuine breakthroughs.

For further reference log on to : doi:10.1001/jama.2018.3264

Source: With inputs from JAMA

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