Restoring cerebellar circuit function to treat ataxia

This technology identifies and functionally targets cerebellar circuit defects, specifically climbing fiber-Purkinje cell (CF-PC) synapses, to restore cerebellar functions and alleviate ataxia symptoms.

Unmet Need: Linking climbing fiber-Purkinje cell degeneration to ataxia symptoms

Cerebellar degeneration leads to severe ataxia symptoms such as imbalance, frequent falls, and loss of motor coordination. Current treatments manage symptoms but fail to address the root cause of the disease. In patients, climbing fiber-Purkinje cells (CF-PC) undergo early synaptic pruning followed by neuronal loss at later stages. However, the causal link between synaptic circuit changes and clinical symptoms remains unclear, limiting the development of effective therapies.

The Technology: Circuit-repair strategy targeting CF-PC synapses

The technology demonstrates that loss of climbing fiber-Purkinje cell (CF-PC) synapses is a key driver of disrupted cerebellar function and ataxia symptoms. It identifies cerebellar alpha rhythm as a biomarker of circuit integrity and shows that restoring CF-PC synaptic activity normalizes cerebellar alpha rhythm and alleviates ataxia symptoms. This technology opens the door to therapies for cerebellar degeneration and other neurological disorders involving synaptic loss.

This technology has been validated in mouse models.

Applications:

• Therapeutic strategies for ataxia and cerebellar neurodegeneration
• Use cerebellar alpha rhythm as a biomarker
• Preventing memory loss

Advantages:

• Restores climbing fiber-Purkinje cell (CF-PC) synapse function
• Prevents CF-PC pruning progression
• Supports stage-specific assessment of cerebellar circuit dysfunction
• Alleviates clinical symptoms

Lead Inventor:

Sheng-Han Kuo, M.D.

Related Publications:

• Lin CC, Fang KC, Balbo I, Liang TY, Liu CW, Liu WC, Wang YM, Hung YL, Yang KC, Geng SK, Ni CL, Driscoll CP, Ruff DS, Kumar A, Amokrane N, Desai N, Faust PL, Louis ED, Kuo SH, Pan MK. “Reduced cerebellar rhythm by climbing fiber denervation is linked to motor rhythm deficits in mice and ataxia severity in patients.” Sci Transl Med. 2025 Feb 26;17(787)

• Chaudhari K, Wang L, Kruse J, Winters A, Sumien N, Shetty R, Prah J, Liu R, Shi J, Forster M, Yang SH. “Early loss of cerebellar Purkinje cells in human and a transgenic mouse model of Alzheimer's disease.” Neurol Res. 2021 Jul;43(7):570-581

Tech Ventures Reference:

• IR CU26133

• Licensing Contact: Jerry Kokoshka