Beccano-Kelly Lab

A breakdown in brain cell communication during Parkinson's disease

Parkinson’s is the fastest growing neurological condition and the second most common neurodegenerative disorder - around 145,000 people live with the condition in the UK. Current therapeutics only treat symptoms so there is an urgent need to find ways to prevent the onset of Parkinson’s and slow progression.

The Beccano-Kelly lab studies communication between brain cells using research models of Parkinson’s. The team are aiming to decipher how miscommunication arises at the earliest stages of Parkinson’s, and find new ways of correcting it before significant loss of cells in the brain, and symptoms appear.

Investigating synaptic health and function over time to identify early-stage modifiable therapeutic targets

In Parkinson’s Disease (PD), the loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc) is attributed to the classic clinical symptoms observed in the disorder. Research has typically been carried out on late-stage pathologywith these works yielding important insights into cell death. However, the most common prescribed treatment, L-DOPA, loses its effectiveness over time, does not prevent further degeneration and can provoke new symptoms. These outcomes are likely a result of targeting the late stages of PD i.e. loss of neurons, rather than the preceeding dysfunction and abberent mechanism. (Beccano-Kelly et al., 2015; Janezic et al., 2013; Matikainen-Ankney et al., 2016; Volta et al., 2017; Yue et al., 2015).

This programme aims to identify the early changes in neuronal function that can be targeted to prevent clinical symptoms of PD. The team focus on longitudinal assessment of genetically faithful models of PD, and assesses the chemo-electric communication and signal transduction of neurons and the molecular functions which directly impact this critical specialised role. This will provide data on the neuronal dysfunction which likely results in the susceptibility seen in PD. Two critical questions in the field of PD research are being addressed: Which phenotypes should be corrected and critically, when? This approach facilitates the unmet need for effective therapies via understanding of the temporal nature of PD.

Main objectives and research goals

1. Determine the progression of synaptic phenotypes in PD hiPSC DA neurons over time.
2. Investigate the longitudinal progression of synaptic phenotypes in genetic PD mouse models.
3. Elucidate the restorative potential of early pharmaceutical intervention in PD on neural network/synaptic dysfunction.
4. Validate synaptically related phenotypes in multiple major mutation and sporadic PD lines
5. Identify early network dysfunction in human PD