Protein fragment to promote neurogenesis

This technology is a dominant-negative fragment of the ATF5 transcription factor that can be used to promote the differentiation and regeneration of several post-mitotic brain cell types in research and central nervous system therapeutics.

Unmet Need: Therapeutic to regenerate mature brain cells

Existing therapies for neurodegenerative conditions target pathologic molecules and attenuate symptoms. However, there are currently no treatments that aim to regenerate neurons or brain cells lost over the course of the disease. Neurons are post-mitotic cells, meaning that following maturation, they generally do not divide further to generate more neurons. Thus, when neurons are lost with neurodegeneration, it is difficult to repopulate these cells to regain function. As such, regenerative therapies are needed to promote neurogenesis and restoration of brain function.

The Technology: Protein fragment that promotes growth and differentiation of brain cells

This technology is a dominant-negative fragment of the ATF5 transcription factor that promotes mature brain cell differentiation from neuroprogenitor cells. ATF5 is normally expressed in neuroprogenitor cells and acts to maintain their undifferentiated and immature state. The dominant negative fragment inhibits ATF5 function and thus accelerates the maturation and differentiation of neuroprogenitors into neurons. As neuroprogenitor cells can give rise to a variety of brain cell types, this protein fragment has been shown to promote differentiation into mature neurons, oligodendrocytes, astrocytes, and even cerebellar granule neurons.

This technology has been validated in vitro and in vivo to investigate the fragment’s ability to drive brain cell development and treat glioma in mice.

Applications:

• Therapeutic for neurologic, neuromotor, and neurodegenerative diseases
• Therapeutic for neuronal stem cell therapy
• Research tool to amplify neurogenesis in vitro and in vivo
• Research tool to study neuronal and brain cell development

Advantages:

• Regenerates post-mitotic brain cell populations
• Relevance to numerous nervous system diseases
• Does not impair healthy, mature brain cells
• Utility in vitro, ex vivo, and in vivo
• Compatible with a variety of delivery systems

Lead Inventor:

Lloyd Greene, Ph.D.

Patent Information:

Patent Pending

Related Publications:

• Cates CC, Arias AD, Nakayama Wong LS, Lame MW, Sidorov M, Cayanan G, Rowland DJ, Fung J, Karpel-Massler G, Siegelin MD, Greene LA, Angelastro JM. “Regression/ eradication of gliomas in mice by systemically-deliverable ATF5 dominant-negative peptide.” Oncotarget. 2016 Mar 15;7(11):12718-30.

• Lee HY, Angelastro JM, Kenney AM, Mason CA, Greene LA. “Reciprocal actions of ATF5 and Shh in proliferation of cerebellar granule neuron progenitor cells.” Dev Neurobiol. 2012 Jun;72(6):789-804.

• Mason JL, Angelastro JM, Ignatova TN, Kukekov VG, Lin G, Greene LA, Goldman JE. “ATF5 regulates the proliferation and differentiation of oligodendrocytes.” Mol Cell Neurosci. 2005 Jul; 29(3):372-80.

• Angelastro JM, Mason JL, Ignatova TN, Kukekov VG, Stengren GB, Goldman JE, Greene JE. “Downregulation of activating transcription factor 5 is required for differentiation of neural progenitor cells into astrocytes.” J Neurosci. 2005 Apr 13; 25(15):3889-99.

• Angelastro JM, Ignatova TN, Kukekov VG, Steindler DA, Stengren GB, Mendelsohn C, Greene LA. “Regulated expression of ATF5 is required for the progression of neural progenitor cells to neurons.” J Neurosci. 2003 Jun 1;23(11):4590-600.

Tech Ventures Reference:

• IR 1416, 1649, CU13345, CU18385

• Licensing Contact: Jerry Kokoshka