Hope4Livi’s Research Goals

G947R AHC Research Roadmap:

1. Create a G947R AHC “worm model” (C. elegans) - Project Initiated!

• Dr. Anne Hart, Ph.D., Professor and Chair of Neuroscience at Brown University, & Diana Wall (Ph.D. trainee) https://www.thehartlab.org/

• Create a gene edit in worms that is representative of the G947R AHC mutation – Completed!

• Characterize the G947R AHC worm model and compare this to the other AHC variants (D801N, E815K, L839P) - Underway!

• Evaluate assays that may be useful for future drug screens, using experiments conducted for the other AHC worm models - Upcoming!

Budget: $16,259 - Funding Secured!

Estimated timeline: 8 – 12 months

- This project will teach us more about how the G947R mutation affects a living organism (other animal models include mice, flies, frogs, etc.). Behavioral and functional endpoints have already been identified in the worms in a previous study. To learn more about this see Dr. Hart’s previous publication http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5148073. Efforts are already underway to explore other AHC patient mutations in the worm. This work will enable us to compare the G947R mutation to the other patient mutations, using the same model system.

2. Create a G947R AHC “mouse model” – Project Initiated!

Estimated timeline: 12-18 months

2b. Evaluate the effect of a novel genetic medicine in the G947R mouse model under development. - Funding needed!

Estimated budget: $250,000 - Fundraising!

Estimated timeline: 12-18 months

- There have been several exciting therapeutic approaches evaluated in AHC mouse models very recently. Much of this work has been led by RAREHope (prev. Hope For Annabel), For Henry AHC, CureAHC, and AHCF. We must determine which therapies work best for each AHC mutation type using this unique mouse model. There have been several exciting therapeutic approaches evaluated in AHC mouse models very recently. We must determine which therapies work best for each AHC mutation type using this unique mouse model.

3. Encourage patient participation in registries to understand AHC symptoms and severity - Underway by AHC partners (Hope For Annabel)

• Even though there are many therapies currently being explored, none of them can proceed into clinical trials without a better understanding of the disease in AHC patients.

• As each of these therapies continues to make advancements the role of patients, and their involvement, in patient surveys and natural history studies becomes even more critical.

• If you have a loved one affected by AHC please consider participating in any or all the below studies if you are eligible. The information that we learn from these efforts will make it is easier to conduct and run clinical trials as these promising therapies make progress.

Estimated timeline: Ongoing