Lixte Teams Up With FAST to Support Preclinical Studies of LB-100

Lixte Biotechnology Holdings is teaming up with the Foundation for Angelman Syndrome Therapeutics (FAST) to advance preclinical studies investigating its proprietary lead compound, LB-100, as a potential treatment for Angelman syndrome.

The studies will be led by David Segal, PhD, and Jill Silverman, PhD, two renowned leaders in Angelman research, and carried out at the University of California, Davis School of Medicine and the MIND Institute. 

“FAST is excited to work with Lixte in pursuit of our mission to identify safe and effective therapeutics for Angelman syndrome,” Paula Evans, chairperson of FAST, said in a press release. “This collaboration is yet another example of how a patient organization can offer a pharmaceutical company the tools and expertise necessary to evaluate therapies for a rare disease population.”

LB-100 is a highly selective and potent inhibitor of protein phosphatase 2A (PP2A), an enzyme responsible for removing phosphate groups from other molecules, and is currently being investigated as an add-on therapy for the treatment of solid cancers. By blocking this enzyme, LB-100 prevents cancer cells from repairing their DNA, making them more vulnerable to cancer-killing agents.

A recent study published in the journal PNAS suggested that the loss of the maternal copy of the ubiquitin protein ligase E3A (UBE3A) gene, which causes Angelman syndrome, can lead to an overactivation of PP2A.

When researchers treated a mouse model of Angelman with pharmacological inhibitors of PP2A, they found the treatment eased symptoms in the mice and helped reduce some of the morphological and structural defects present in brain nerve cells (neurons).

In addition to shedding new light into some of the molecular mechanisms at play in Angelman, this study also suggested that medications that are able to block the activity of PP2A, like Lixte’s LB-100, may potentially be used to treat Angelman.

“This was a completely unanticipated finding,” said John S. Kovach, CEO of Lixte. “We can only hope that LB-100 may be of benefit to patients afflicted with this devastating life-long disorder.” 

If the new preclinical studies confirm the findings of this earlier study, both Lixte and FAST have agreed to discuss the possibility of future collaborations to investigate LB-100’s therapeutic potential in patients with Angelman.