Brainwave-Discovery Solutions
Challenges in modern CNS drug discovery:
Pharmaceutical and biotechnology companies need to get more CNS drugs to market to meet rapidly growing demand. However, current R&D pipelines are yielding fewer new FDA approved drugs than before despite increased investment. Choosing the right target – and finding new, innovative targets – is a crucial step to drug development. Genomics has provided vast numbers of CNS proteins that could be new candidates for future therapeutics, but deciding which of these to focus limited research budgets on is a very difficult challenge.
A limiting factor in CNS drug development is that very early in the process, new molecules (targets or candidate drugs) need to be tested in a living brain - cellular models while useful can only go so far. Existing approaches (rodent models) are slow, expensive and under ever-increasing ethical pressure such that reliance on them stifles innovation. These issues are even more critical for indications that require long-term treatment such as neurodegenerative disorders, or the creation of complex genetic models where multiple genes need to be manipulated.
What does Brainwave-Discovery offer?
BrainWave-Discovery specialises in the rapid development of in vivo brain assays for chemicals acting on a human CNS targets selected by our clients. We use our expertise in “humanising” transgenic fruit flies (Drosophila) to deliver the desired human molecule to a specified subset of nerve cells in the insect brain. We introduce the human protein into special strains adapted for the Brainwave assay, so that changes in brain activity due to the action of candidate drugs on this human protein are detected as changes in light emission from the brain – or as changes in behaviour.
As an example, when we add the human version of the PDE4B gene into the fly brain we observe that brain activity in the fly now becomes sensitive to the application of human drugs which have minimal effects (if any) on the un-modified fly brain.
![[PDE4B trace data]](pde4b.jpg)
The graphs above show brain activity (y axis) over time (x axis) using the Brainwave assay (the oscillations in activity are a natural phenomena associated with the learning and memory circuits the assay exploits). The response of a normal fly (left) and a humanised BWD fly (right) to the application of rolipram (indicated by the red line) is shown. The normal fly response is minimal, delayed and only observed in a subset of samples. The humanised response is an instant cessation of reported activity in the target neurons.
What are the benefits of Brainwave-Discovery's approach
BrainWave-Discovery provides early in vivo data which can contribute significantly to the decision making process at a fraction of the cost and much faster than mammalian models for early stage research. Key benefits include:
- Fast and cost-effective – more data for the dollar
- Real, live brain data (physiology and behaviour)
- Capacity to study complex interactions/pathways
- Free of ethical and regulatory strictures – reduce use of mammals
- in vivo data brought in earlier to research supports better informed decisions
Depending on the complexity of the model, generating a new model rodent can take anywhere between 12 to 24 months before the first brain data is available. In comparison, we can go from sequence file to brain data as quickly as just 3 months.
We have more information on specific Brainwave Science available.
Benefits that span the R&D pipeline
At BrainWave-Discovery we believe that a Drosophila in vivo CNS study should be an early component of modern drug development programs providing early brain data to improve the decision processes. BrainWave-Discovery is ready to help our clients reap the benefits of this technology.
Our customers scientists get early unique data for a wider range of interesting proteins helping them innovate. They can achieve in 1 year (budget and time) what currently stretches out over 5. BWD leverages decades of molecular genetic research into Drosophila - we think of it as more than an assay rather a molecular research lab in a fly brain.
Research managers get rapid, low cost data to improve decision making for prioritising disease related proteins / targets, potentially interesting compounds / candidates, rejecting ineffective compounds earlier and faster pre-clinical development cycles. In summary, alongside their scientific teams they gain increased scope for novel drug development.
Research Directors/VPs gain more potential to explore high value, novel drugs and targets within existing budgets. BWD achieves whilst reducing the reliance on mammalian models and in some cases (e.g. some neurodegenerative indications) can partly replace mammalian models.
Business and Finance Directors gain the opportunity to bring novel drugs to market that would be lost earlier in existing research pipelines while reducing cost and animal usage.
Specific benefits of the Brainwave-Discovery approach in anti-neurodegenerative and cognitive drug discovery
- Fast cost-effective model provision
- Multi-gene humanized models
- High throughput primary drug screen
- Automated behavioural confirmation screen
Learning and memory
- Multiple automated paradigms
- Multi-gene and pathway analysis
- Highest learning assay throughput available
- Lab in a fly for next steps
How does Brainwave-Discovery operate?
We know each R&D unit works in its own unique way and there is no one size fits all solution. Our preferred mode of operation is that we will visit your scientists to learn where we can best position Brainwave-Discoveries technologies to complement and enhance your existing knowledge base and pipeline. To arrange a visit and presentation from our senior scientists, or just to find out more, please contact us.
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