Dr. Aasef G. Shaikh MD,PhD

Functional Electrical Stimulation Institute

Membranes and Models - Towards Targeted Therapy of Opsoclonus

Grant Sponsor

Funded in partnership with The Viswanatha Family + Friends

Opsoclonus is the chaotic involuntary shaking of the eyes leading to a significant visual handicap and can be seen in those with various forms of cancers. It is difficult to treat opsoclonus, and available treatments have significant side effects and unpredictable responses. Opsoclonus typically occurs as a result of the body’s attack on one’s own brain cells. But how or why the immune attack on brain cells causes opsoclonus is still unknown. One hypothesis is that specific brain cells get excited by the immune attack and are unable to ‘turn off’ causing the brain circuit to reverberate. Those reverberations then manifest as opsoclonus. Dr. Aasef is planning to test that hypothesis using his Powered by Pablove grant and well developed computer simulation models to further our understanding of opsoclonus and identify potential treatment targets. 

 

In Dr. Shaikh’s own words:

Opsoclonus is the chaotic involuntary shaking of the eyes leading to a significant visual handicap. Typically occurring as a result of the body’s attack on one’s own brain cells, opsoclonus can be seen in those with various forms of cancers. It is difficult to treat opsoclonus, and available treatments have significant side effects and unpredictable responses. Despite significant therapeutic challenges, it is still unknown how immune attack on the brain cells causes opsoclonus. We propose that opsoclonus is due to excessive excitation of specific types of brain cells, that causes the brain circuit to reverberate. The oscillations then manifest in opsoclonus. We will examine this question by complementary interdisciplinary approaches. We will first examine which types of proteins, that is ion channels and neurotransmitters, are present in brain cells that putatively cause opsoclonus. Then we will examine how such proteins are altered in brain cells in patients with opsoclonus. Once we know the profile of such proteins, we will refine computer simulations of the opsoclonus and further predict which type of drug therapy can be most effective in the treatment of opsoclonus by counteracting the ill effects of abnormally functioning cell proteins. The combined approach suggested in our proposal is unique and it has broad implications for understanding the mechanistic basis for opsoclonus and developing rational therapies.

Awarded in 2022