Developing novel therapeutic targets for neurological conditions in Australia
Questions to be answered
Variations in genes that regulate brain connectivity cannot be restored using current therapeutics. However, targeting synaptic homeostasis, or normal signaling, is potentially an important therapeutic mechanism that could alleviate symptoms without the need to change neuronal circuitry. Our work is examining this concept by testing whether we can develop therapeutics that do not directly target the mutant protein Homer but instead target the signalling mechanisms regulated by Homer. This work will not only have implications for the Homer proteins, but also other related proteins that are also implicated in conditions such as autism and depression.
Goal One (COMPLETED)
We will examine how the Homer gene variant disrupts normal function in synapses in lab-based studies.
Goal Two (ONGOING)
We will use ISPC - Induced pluripotent stem cells grown from the skin or blood of affected individuals and converted into neurons - to study basic nervous system function of affected individuals and recapitulate the pathophysiological and the pharmacy-responsive properties of the “Homer Brain”.
We will use electrophysiological testing measures to develop targeted precision based medicines to treat the neuronal complications associated with Homer variants with the potential of these targets being efficacious in treating other neurological diseases involving calcium signalling and scaffolding proteins.
Goal Three (IN PROGRESS)
We will then use our evidence base derived from our first 2 goals to increase awareness of the implications of Homer variants and other rare scaffolding proteins in neurological conditions, building a suite of tools to assist patients and their families to reach better outcomes.
Timeline
YEAR 1 ('22)
YEAR 2 ('23)
YEAR 3 ('24)
YEAR 4 ('25)
1
Demonstrate effect of Homer in pre and postsynaptic signaling in vitro
2
Determine the effects of Homer variants on circuit formation in vivo
3a
Isolate,characterise and validate proband IPS cells
3b
Use proband IPSCs to study synaptic signaling and drug rescue
Mission
Drive research to better understand Homer and other rare genes and their role in neurological disease and improve outcomes for people with these variants, their families and carers
Vision
Our knowledge, translated into practice, delivers demonstrable improvements in the capacity and lifetime journeys of people affected by Homer and rare gene variants
Goal/Pillar 1
Facilitate a leading research program
- Establish and maintain a scientific advisory committee.
- Design a comprehensive research framework and multi-year research program.
- Enable and monitor the agreed, multi-year and multi-level research program.
Goal/Pillar 2
Enhance the translation of knowledge
- Contribute to scientific evidence-base and literature.
- Investigate and, where appropriate, progress the clinical diagnosis of Homer variants.
- Define the interplay of Homer and other rare gene variants in broader neurological diseases.
Goal/Pillar 3
Build awareness and education
- Enhance baseline communications platforms and content.
- Locate, connect with and maintain a network of people with Homer and other rare gene variants and their families.
- Design and deliver an education program for the general public 4. Build awareness of the implications in other neurological diseases.
How can you help?
We welcome scientific collaboration and people seeking information about The Homer Hack.
You can also donate to The Homer Hack Neurodevelopmental Research Fund. Your contribution will go to our research goals. All donations are tax deductible.
