Therapeutic interventions for treating vascular malformations

This technology identifies proteasome inhibitors and PI3K/mTOR inhibitors as therapeutic interventions for patients with pathologic vascular malformations.

Unmet Need: Treatment options for resolving vascular malformations

Current patients suffering from vascular malformations have limited treatment options, with no available FDA-approved therapy. While several clinical trials are exploring various candidates including sirolimus, an mTOR inhibitor, these treatment options are expected to require substantially high doses. These doses can exacerbate unwanted side effects, necessitating more precise therapeutic options.

The Technology: Proteasome inhibitors and PI3K/mTOR inhibitors to treat vascular malformations

This technology identifies proteasome inhibitors and PI3K/mTOR inhibitors such as omipalisib as therapeutics for treating vascular malformations. These targets were identified through high-throughput screening of patient-derived endothelial cells, suggesting that treatments will be much more germane to specific molecular pathology. Targeting the proteasome and PI3K/mTOR were revealed to be effective at reducing outgrowth of pathogenic endothelial cells, underscoring them as potential treatments.

This technology has been validated in patient-derived endothelial cell lines.

Applications:

• Treatment for vascular malformations
• Treatment for other types of endothelial proliferative diseases
• Inhibition of endothelial cell proliferation for research studies

Advantages:

• Greater expected efficacy than repurposed therapeutics
• More precise than emerging standard of care
• Lower dose is required for efficacy
• Opportunity for combinatorial therapeutics

Lead Inventor:

Carrie Shawber, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Schonning MJ, Koh S, Sun RW, Richter GT, Edwards AK, Shawber CJ, Wu JK. Venous malformation vessels are improperly specified and hyperproliferative. PLoS One. 2021 May 27;16(5):e0252342

• Davis RB, Pahl K, Datto NC, Smith SV, Shawber C, Caron KM, Blatt J. Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations. Sci Rep. 2018 Dec 20;8(1):17987

• Shawber CJ, Lin L, Gnarra M, Sauer MV, Papaioannou VE, Kitajewski JK, Douglas NC. Vascular Notch proteins and Notch signaling in the peri-implantation mouse uterus. Vasc Cell. 2015 Dec 1;7:9

Tech Ventures Reference:

• IR CU20315

• Licensing Contact: Cynthia Lang