Funded Studies
Study Rationale:
Antisense oligonucleotides (ASOs) are a new type of therapeutic that have promise for treating Parkinson’s disease. They act by modifying the production of specific proteins, such as alpha-synuclein which forms toxic clumps in Parkinson's brains. However, the ability of ASOs to travel from the blood into the brain is poor. To avoid the need to be injected directly into the brain or spinal cord, this project is developing a molecule – brain-penetrating peptide – that can be attached to ASOs to help them enter the brain after intravenous or subcutaneous injection.
Hypothesis:
Attaching a brain-penetrating peptide to an antisense oligonucleotide that targets the alpha-synuclein protein will enable the drug to enter the brain after intravenous injection and reduce the level of alpha-synuclein protein.
Study Design:
We have developed a molecule (brain-penetrating peptide) that has been attached to an antisense oligonucleotide for treating another neurological disease and successfully delivered it into the brain following intravenous injection in mice. Other researchers have successfully developed ASOs targeting the alpha-synuclein protein for Parkinson’s disease, which we will attach to our brain-penetrating peptide. After injecting this therapeutic into mice intravenously, we will assess the effect on the alpha-synuclein protein in the brain. We will also systematically modify the structure of the brain-penetrating peptide molecule to optimize it effectiveness.
Impact on Diagnosis/Treatment of Parkinson’s disease:
Antisense oligonucleotide therapies have the potential to target brain mechanisms that cause Parkinson’s disease and its progression. Making these new treatments effective after intravenous injection would make them accessible to many more people with Parkinson’s and avoid the risks of repeated spinal injections.
Next Steps for Development:
If successful, the brain-penetrating peptide molecule developed here will be coupled to a range of antisense oligonucleotides targeting the brain alpha-synuclein protein, to find the most active combination for development as a new therapy. It could also be coupled to ASOs targeting other brain proteins involved in Parkinson’s disease.