Our Approach
INNOVATIVE AND TARGETED STRATEGY WITH POTENTIAL FOR LIFE-CHANGING TREATMENT
At Parkinnova Therapeutics, our approach is grounded in the latest advances in neuroscience research, including new technologies in genetics and transcriptomics. Through fundamental research, we’ve gained unprecedented insight into the molecular pathways that regulate dopamine production in midbrain neurons, which are crucial in the development of neuro-psychiatric and neurological disorders, such as Parkinson’s disease. Our founders have been at the forefront of these efforts, and are dedicated to translating this knowledge into clinical trial-ready compounds and innovative and targeted treatments for Parkinson’s disease.
Background
CURRENT TREATMENT STRATEGIES FOR PARKINSON'S DISEASE ARE FAILING THOSE WHO NEED LONG-TERM RELIEF
Dopamine is a neurotransmitter that plays a crucial role in regulating movement, motivation, and reward in the brain. In Parkinson’s disease, there is a progressive degeneration of dopamine-producing neurons in a specific area of the brain called the substantia nigra. This results in a reduction in dopamine levels, leading to characteristic symptoms such as tremors, rigidity, and slowness of movement. The imbalance between dopamine and other neurotransmitters in the brain caused by the reduced dopamine levels can further contribute to the motor and non-motor symptoms of Parkinson’s disease.
The current treatment strategies for Parkinson’s disease involve dopamine replacement therapy, which administers medications like levodopa and dopamine agonists to increase dopamine levels and restore dopaminergic neurotransmission. Although initially effective, the medications’ effectiveness decreases over time, leading to side effects such as dyskinesia and motor fluctuations. As a result, dopamine replacement therapies are burdened by limitations and lack long-term efficacy.
Our strategy
A UNIQUE AND TARGETED Dual-action APPROACH
Meet PDE11A, an enzyme uniquely enriched in midbrain dopamine neurons. By inhibiting PDE11A, we not only enable targeted dopamine replenishment, effectively addressing Parkinson’s motor symptoms, but also offer disease-modifying effects, slowing down disease progression. This dual-action approach distinguishes us from conventional treatments.
The Biology
UNLOCKING THE ON-OFF SWITCH OF DOPAMINE PRODUCTION
Dopamine production in the Brain: Tyrosine Hydroxylase is Rate-Limiting
Dopamine synthesis involves two enzymes: tyrosine hydroxylase (TH) converts L-tyrosine to levodopa, and AADC transforms levodopa into dopamine. The rate-limiting step is TH activity. In other words, the rate at which dopamine is produced is determined by the activity level of TH.
The 'ON-OFF Switch' of Dopamine Production: TH S40 Phosphorylation
Phosphorylation (p) of tyrosine hydroxylase (TH) at Serine 40 (S40) determines TH’s activity. When S40 is phosphorylated, the enzyme is activated, and the dopamine synthesis process initiated. Thus, TH S40 phosphorylation acts as the pivotal ‘ON-OFF switch‘ controlling dopamine production.
Boosting Dopamine Production: PDE11A Inhibition & TH Activation
TH activation can be mediated via PDE11A . PDE11A inhibition prevents cyclic nucleotide degredation, resulting in S40 phosphorylation and activation of dopamine production. PDE11A inhibition presents a novel mechanism of action for dopamine replenishment in Parkinson’s.
Help us bring innovative treatments to those in need.