Adrenoleukodystrophy (ALD), also known as X-linked ALD (X-ALD), is caused by mutations in the ABCD1 gene, which contains the instructions to produce a transporter protein that allows fatty molecules, called very long‐chain fatty acids (VLCFA), to be degraded. As a result of the mutations, the transporter does not work as intended and fatty molecules accumulate in regions like the brain, spinal cord, and adrenal glands.
Another receptor for VLCFAs, called ABCD2, can also promote the breakdown of fatty molecules. VK0214 enhances the activity of a receptor, called the thyroid beta receptor, that regulates ABCD2 levels and can lead to VLCFAs being broken down as intended.
Preclinical data in a mouse model of X-ALD showed that treatment with oral VK0214 significantly reduced the levels of VLCFAs in the animals’ blood compared to untreated mice after 25 weeks. This reduction in VLCFA levels was also detected in the animals’ liver and central nervous system (CNS, the brain and spinal cord).
Researchers also confirmed that treatment with VK0214 increased the levels of the alternative transporter, ABCD2, by 35% in the brain and 262% in the liver compared to control animals.
The results were presented in a poster, “Long-term dosing with the thyroid hormone receptor agonist VK0214 reduces VLCFA levels in plasma and tissue in an in vivo model of X-inked adrenoleukodystrophy,” at the 87th Annual Meeting of the American Thyroid Association in 2017.
At the time, Brian Lian, PhD, chief executive officer of Viking, called the results “particularly exciting as they demonstrate the first evidence of VK0214’s effects in CNS tissues.”
“The observed reductions in brain and spinal cord VLCFAs, combined with the stimulation of brain ABCD2 expression suggest potential benefits in tissues that are difficult to penetrate and especially prone to degeneration in X-ALD. In addition to the potent and durable reductions of plasma VLCFAs, we believe these results provide compelling support for the continued evaluation of VK0214 in this setting,” Lian added.
VK0214 was designated an orphan drug by the U.S. Food and Drug Administration as a potential X-ALD therapy in December 2016. Orphan drug status aims to encourage the development of treatments for rare and serious diseases through incentives such as seven years of market exclusivity and exemption from FDA application fees.
Viking expects to launch its clinical trial evaluating VK0214 for X-ALD early next year.
“We continue to advance our … work for VK0214 for the treatment of X-ALD, and expect to initiate a Phase 1 clinical trial in the first half of 2020,” Lian said in the recent press release.
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