The Blechman Foundation’s mission is to fund research to identify neuroprotective agents that provide disease-modifying effects in PD patients. This is the most promising way to slow or stop PD progression and prevent the development of intolerable disability. This report highlights developments in neuroprotective research in 2014.
There are many challenges to delivering a neuroprotective agent for PD patients, and the Foundation is right in the middle of the effort to meet those challenges. These challenges include: (1) the uncertainty about the cause of PD and precisely what to target; (2) a reliable animal model to test putative neuroprotective agents that accurately predict results in PD patients; (3) insight about the dose to use in clinical trials and the patient group to study; (4) a clinical trial design that reliably differentiates disease-modifying and symptomatic effects and that is acceptable to regulators; and (5) the cost and time of the development program. (Stocchi etc., Mov. Disord. 2013; 28:3-7.)
The Foundation’s 2014 grant targets neuroprotective research at the Pittsburgh Institute of Neurological Disorders. We are optimistic that the results of that research will be reported in a forthcoming scientific journal. Besides research funded by the Blechman Foundation, other important scientific work was done in 2014 to take us one step closer to identifying neuroprotective agents.
One 2014 paper reports on several important advances in understanding the pathways that lead to cell dysfunction and cell death in PD. (Schapira etc., Mov. Disord. 2014; 384:545-555.) This research has led to the identification of molecular targets for intervention designed to slow or reverse PD. Another 2014 paper reports on a new and effective means to reduce the excessive production of alpha-synuclein protein in neurons. (Cooper etc., Mov. Disord. 2014; 29:1476-85.) Excessive alpha-synuclein proteins form clumps in brain cells called Lewy Bodies, which are a characteristic pathological feature of PD in brain cells. In PD, alpha-synuclein proteins spread from damaged, dying cells to healthy cells and spread the disease. Decreasing alpha-synuclein protein thus may delay or halt PD progression.
Another 2014 paper reported on a breakthrough drug that acted on a cellular target to restore dopaminergic function in a mouse model of PD. (Francardo etc., Brain 2014; 137:1998-2014.) This is important because PD occurs when dopaminergic function is impaired. Another highly novel paper in 2014 reported that a protein made by a virus can be harnessed and turned into a treatment to protect mitochondria in dopamine neurons in PD models. (Szelechowski etc., Nat. Commun. 2014; 5:5181.) Mitochondrial dysfunction is a common feature of PD, and agents that protect mitochondria have strong therapeutic potential. Another 2014 paper identified a pharmacological chaperone that provided neuroprotection for mice with PD. (Richter etc., Neurotherapeutics 20 July 2014.)
The Foundation believes that it is focusing its scientific support in the place where it can do the most and soonest good for PD patients: neuroprotective research.