CORRECTING and REPLACING IntraBio Announces Publication of New Research Showing a Direct, Bidirectional Effect on Lysosomal Function with Levacetylleucine

AUSTIN, Texas--(BUSINESS WIRE)--The last paragraph in the release after the boilerplate has been removed.

The updated release reads:

INTRABIO ANNOUNCES PUBLICATION OF NEW RESEARCH SHOWING A DIRECT, BIDIRECTIONAL EFFECT ON LYSOSOMAL FUNCTION WITH LEVACETYLLEUCINE

IntraBio today announced the publication of new research in PLOS ONE describing a newly identified way that levacetylleucine, the active ingredient in AQNEURSA®, acts directly on cellular lysosomal function.

The study, conducted by researchers at the University of Oxford, examined the drug's effect on Transcription Factor EB (TFEB), the master transcriptional regulator of lysosomal biogenesis and autophagy - the cellular systems responsible for clearing damaged proteins and lipids. Uniquely, a biphasic action of levacetylleucine on TFEB activity was identified, whereby levacetylleucine normalizes TFEB, activating its translocation in disease models when there is a deficiency, but also downregulating TFEB in models where it is overstimulated, thereby maintaining cellular homeostasis. This biphasic action is essential for a therapeutic effect and to ensure TFEB is not persistently overexpressed.

The effect was also shown to be stereospecific and rapid in onset, appearing within approximately one hour. Only the purified L-enantiomer (levacetylleucine) was active; the D-enantiomer and the racemic mixture produced no effect, reinforcing the distinct pharmacology of the purified L-enantiomer used in AQNEURSA.

Levacetyllecuine has been previously identified to have polypharmacolohical effects, with direct action on other cellular organelles such as the mitochondria, where it normalizes energy metabolism (cellular energy production). These novel findings provide the first evidence that levacetylleucine directly modulates lysosomal function. As TFEB dysregulation is implicated in a range of neurodegenerative and neurodevelopmental conditions, these findings provide further evidence of the potential applicability of levacetylleucine as a broad treatment for rare and common neurological conditions.

“We have not previously observed a mechanism that regulates TFEB in this bidirectional, homeostasis-restoring manner,” said Professor Antony Galione, FRS FMedSci, senior and corresponding author and Professor of Pharmacology at the University of Oxford. “Rather than simply activating or inhibiting the pathway, levacetylleucine appears to recalibrate lysosomal activity according to the state of the cell to match its needs – in effect, acting as a molecular thermostat. These findings are remarkable and may have important implications for diseases characterized by lysosomal and mitochondrial dysfunction.”

The full publication, “N-acetyl-L-leucine normalizes Transcription Factor EB activity by stereospecific bidirectional modulation in a HeLa cell model of Niemann-Pick disease type C,” can be accessed here: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0353834

ABOUT INTRABIO

IntraBio Inc. is a global biopharmaceutical company headquartered in Austin, Texas, focused on developing and commercializing targeted therapies for rare and common neurological, neurodevelopmental, and mitochondrial diseases. IntraBio’s platform technologies are built on decades of scientific research and collaboration with leading institutions worldwide, including the University of Oxford and the University of Munich.