The current research goals of CAMK2 Therapeutic Network are to:

— 1 —

Work toward finding current FDA approved drugs to lessen symptoms our children are experiencing (termed drug repurposing), and

— 2 —

Work toward genetic therapies both to lessen symptoms and with a goal toward cure.

Primary goal: Support the science of drug repurposing for CAMK2 disorders so that clinical trials are available two years after funding. Our estimate is that we need $150,000 to $200,000 US dollars to support this effort. Although the expertise is available, without funding, the investigations cannot be done.

The science of drug repurposing will involve 1. Understanding our children’s symptoms and those we most need to improve (likely seizure, agitation, constipation), 2. Cell culture with iPSC (back engineered cells derived from the blood of affected persons) or other cells to better understand the cellular effect of different CAMK2 mutations, and 3. Possibly animal models to assess effects of different CAMK2 mutations with regard to biologic processes, such as seizures, agitation, and bowel motility. Once we have cell models and/or animal models, we can start screening medications that are already FDA approved to see which ones may be able to normalize function. Once we have this information, clinical trials can be designed. With drug repurposing, drugs found to help one child with a CAMK2 gain of function mutation will likely be generalizable to help all kids with CAMK2A, B, G, and D gain of function mutations. Likewise, medications to help a child with one CAMK2 loss of function mutation will likely be generalizable to help all kids with CAMK2A, B G. and D loss of function mutations.

Secondary goal: Fund science working toward gene therapies. With regard to current technology, ASO (anti sense oligonucleotide therapy) is likely the best approach. It will likely take three to five years after funding is initiated before clinical trials can be initiated. We are exploring multiple options to fund this initiative.