Date of Award
Spring 5-2026
Language
English
Document Type
Honors Thesis
Degree Name
Bachelor of Science
Department
Biological Science
Advisor/Committee Chair
Pauline Carrico
Committee Member
Andy Berglund
Committee Member
Ting Wang
Abstract
Myotonic Dystrophy is a rare repeat expansion disorder. It’s a common neurodegenerative disease caused by the mutation of microsatellite repeats in the native genome. Thousands of people worldwide, including hundreds of people in NY, are affected by it. Myotonic Dystrophy also known as DM patients suffer from insulin resistance, reduced fertility, cognitive impairment, and cardiac dysfunction but not limited to these symptoms. The onsets are produced from the formation of toxic RNA that recruits MBNL1 (Muscle Blind Like) proteins leading to functional inactivation of the protein, disrupting the downstream pathways of protein processing. The molecular hallmark of the disease is mis-splicing of exons in alternative splicing of pre-mRNA. The formation of toxic RNA and the severity of onset depend on the nucleotide repeats of the DNA theoretically. There is no FDA approved therapeutic to treat this genetic disease currently. However, many therapeutics are under research for Myotonic Dystrophy 1 targeting disease mechanisms from various aspects. One of them includes diamidine compounds that targets to rescue dysregulated splicing events in DM. Pentamidine, heptamidine and furamidine are part of the diamidine family molecules that have been shown to decrease the expression of toxic RNA causing gene and upregulate MBNL1 protein. Modified Polycyclic Compounds or MPCs are a type of small molecule that shares a similar structure to those compounds that have also been shown to be effective against Myotonic Dystrophy type 1 or DM1 recently. MPC03 and MPC04 have exhibited the highest effectiveness in severe cases of DM1 with higher repeat lengths of nucleotides among numerous MPC structures. Our focus was on MPC03 for this project. We were able to synthesize a small batch of this compound. We also found out that MPC03 can be effective in DM1 cell lines containing shorter repeats with shorter treatment duration.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Ahmed, Sanjida, "Modified Polycyclic Compound Synthesis and Screening in Myotonic Dystrophy Type 1" (2026). Biological Sciences. 111.
https://scholarsarchive.library.albany.edu/honorscollege_biology/111