Parkinson’s Disease

• Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. Performed market assessment for some of the latest (2024) treatments for PD. (1) Produodopa—a new treatment approved by NICE for people with PD who experience movement-related symptoms. It’s delivered continuously by a small pump that’s inserted under the skin. (2) Vyalev—(foscarbidopa and foslevodopa) is a solution of carbidopa and levodopa prodrugs for 24-hour continuous subcutaneous infusion that’s been approved for PD motor fluctuations. (3) Crexont—a new formulation of immediate- and extended-release levodopa with carbidopa. (Levodopa is converted in the brain to dopamine, the chemical that goes missing in PD; carbidopa helps levodopa get into the brain and decreases side effects.) (4) Safinamide— a novel experimental drug that shows potential in the treatment of PD and epilepsy. It works by blocking voltage-dependent sodium and N-type calcium channels, inhibiting glutamate release. (5) Methylphenidate and atomoxetine—noradrenaline reuptake inhibitors that are being investigated for their effects on balance and gait. (6) Levodopa inhalation powder—a formulation of levodopa that can be used as needed when medication effects wear off. (7) Focused ultrasound—a minimally invasive treatment that uses beams of heat to generate acoustic energy and precisely target areas of the brain that control voluntary movement. (8) Deep brain stimulation—a surgical procedure that involves implanting electrodes in the brain to deliver electrical impulses and disrupt abnormal circuitry. (9) Bemdaneprocel—a cell therapy that’s showing positive results in clinical trials, including improved motor function and symptom control.
• ASPIRO Clinical Trial (Phase 1 & 2a). Autologous dopamine neuron progenitor cells (DANPCs) are surgically implanted into the putamen of patients with PD. The putamen is a round structure located at the base of the forebrain (telencephalon). The putamen and caudate nucleus together form the dorsal striatum. The putamen is a subcortical structure that is part of a group of structures known as the basal ganglia or basal nuclei. (“Basal nuclei” is technically more accurate, because “ganglia” usually refers to clusters of nerve cell bodies outside the central nervous system.) The putamen is adjacent to the globus pallidus and together they are sometimes referred to as the lentiform or lenticular nucleus. The putamen is involved in (reward-related) learning and motor control, including speech articulation, language functions, reward, cognitive functioning, and addiction.
  • PD affects the putamen in several ways, including Dopamine depletion—PD causes a gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which leads to a depletion of dopamine in the putamen. This depletion causes motor dysfunction. Atrophy—the putamen can undergo atrophy, which is associated with motor symptoms and cognitive status.  Shape changes—The putamen can undergo shape changes, particularly in the right putamen. Decreased activity.

• Other parts of the brain that are affected by PD include the caudate and nucleus accumbens, which can also experience dopamine depletion. Dopamine replacement therapy can partially restore motor function, but long-term treatment can lead to motor complications.
• The effect on PD symptoms, safety and tolerability, and cell survival are assessed for 5 years post-transplant (with MRI and PET imaging scans of the brain). Safety and tolerability are assessed annually for an additional 10 years via telephone call (total follow-up of 15 years).
• The biologic implanted, ANPD001, is an experimental product derived from autologous skin cells converted to induced pluripotent stem cells. The stem cells were differentiated into DANPCs. Dose escalation will be achieved by bilateral injection of these DANPCs into the putamen.
• Primary outcome measures: incidence and severity of treatment emergent adverse events (TEAE) and serious adverse events. Secondary outcome measures: “ON” time without troublesome dyskinesia [Time Frame: 1 year (primary follow up) and 5 years (long term follow up)]. Post-injection change in Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II (Activities of Daily Living – ADL) and Part III (motor score) in the ON state. “ON” time or ON state simply means the period when the Parkinson’s medication is effectively managing symptoms, allowing for normal movement with minimal side effects.
•  The anterior commissure (AC) is a bundle of nerve fibers that connects different parts of the brain and is important for communication between the brain and the body. The AC is a white matter tract that connects the two cerebral hemispheres across the midline, in front of the fornix columns. Although PD is primarily considered a gray matter (GM) disease, alterations in white matter (WM) have gained increasing attention in PD research recently. Recent evidence from MRI scans reveals correlations between WM changes and specific PD symptoms, and these WM abnormalities may be caused by changes of oligodendrocyte (OLs)/myelin in PD.