The American Academy of Neurology (AAN) Annual Meeting – Parkinson’s Disease Updates

APDA Research The American Academy of Neurology (AAN) Annual Meeting – Parkinson’s Disease Updates

The American Academy of Neurology (AAN) Annual Meeting is taking place this week in Los Angeles, California. This is a meeting of neurologists and neuroscientists across all subspecialties of Neurology, including Movement disorders/Parkinson’s disease. At the meeting, research findings are presented, often for the first time. APDA is there and will be reporting exciting news and highlights to you all week. Check back often and stay tuned for updates!

April 27, 2018

  • A case series presented 5 patients with advanced Parkinson’s disease, initially treated with deep brain stimulation (DBS), who then required initiation of Carbodopa/Levodopa intestinal gel (Duopa). Treatment with duopa was very successful in this cohort, demonstrating that duopa can be used as a rescue therapy even after DBS (P6-027).
  • The ‘white matter’ of the brain refers to areas through which connections travel from one brain region to another. Increase in aerobic fitness in patients with PD correlated with improvements in MRI measurements of white matter integrity. These results may shed some light on the mechanisms behind why exercise improves motor and non motor symptoms in Parkinson’s disease (P6-029)
  • Data was presented on wearable sensors that were developed in a collaboration between IBM and Pfizer. The sensors were able to distinguish whether the wearer was in the ON or OFF state, which could help in monitoring drug response during a clinical trial (P6-086).

April 26, 2018

  • Lysosomal enzymes break down molecules that can be harmful to the cell. Parkinson’s disease may be caused in part by dysfunction of these enzymes, of which glucocerebrosidase (GBA) is the most well-studied. This abstract presented data showing that the activity of another lysosomal enzyme, alpha galactosidase, was decreased in PD cases as compared to controls, furthering our understanding of the mechanisms that contribute to PD and opening up another possible therapeutic target (S45-005).
  • Whereas in PD, alpha-synuclein abnormally accumulates in neurons, in the parkinsonian syndrome Multiple System Atrophy (MSA), the misfolded alpha-synuclein is found in the oligodendrocytes, the cell type that forms the myelin sheath surrounding the neurons. Researchers were able to demonstrate that incubating healthy oligodendrocytes with fibrils of alpha-synuclein induced Lewy body formation within the oligodendrocytes, shedding light on potential mechanisms of how Multiple System Atrophy develops (S45-004).
  • ITI-214 is a drug under development by Intra-Cellular Therapies, Inc for treatment of motor symptoms as well as cognition in Parkinson’s disease. It acts as an inhibitor of phosphodiesterase type I (PDE1), an enzyme involved in cell signaling within the neuron. In disease states, PDE1 levels tend to be high, leading to the possibility that reducing the activity of the enzyme could help restore normal neuronal function. ITI-214 showed promise in rodent models of both motor and non motor symptoms of PD. A phase I/II study of this drug for PD is currently recruiting participants (P5-067).
  • Nilotinib is a chemotherapeutic agent, used mostly to treat patients with certain types of leukemia. In 2015, it was tested in PD patients in a small, open label study, with the theory that the drug could help clear alpha-synuclein deposition from neurons. A larger study is currently underway and the study design of that Phase 2A study for Nilotinib was presented. Two doses of Nilotinib, 150 mg and 300 mg, are being tested. Initially, Cohort 1, consisting of moderate to advanced PD patients, is being recruited. Once a safe and tolerable dose in determined in Cohort 1, Cohort 2, consisting of early PD patients, will be recruited.

April 25, 2018

  • Exenatide, a glucagon-like peptide-1 agonist, approved for treatment of diabetes, was shown in a small study in 2017 to have motor benefits in Parkinson’s disease. The benefits were sustained beyond exposure to the drug, raising the possibility that it could be a neuroprotective agent. The current study investigated possible molecular mechanisms by which exenatide could work in Parkinson’s disease and suggested that exenatide modulates neuronal insulin signaling in Parkinson’s disease (S27-002).
  • Results were presented of a trial for BIIB092, a monoclonal antibody against Tau for the treatment of the parkinsonian syndrome, Progressive Supranuclear Palsy (PSP). The antibody was well tolerated and demonstrated marked suppression of free extracellular Tau in trial participants. There are currently no therapeutic options for PSP, which makes this type of research particularly exciting (S27-004).
  • A summary was presented of a large-scale registry of patients implanted with the new VERCISETM deep brain stimulation manufactured by Boston Scientific. A total of 200 patients are enrolled in the registry. A 36.2% improvement from baseline in the Movement disorder society-United Parkinson Disease Rating Scale (MDS-UPDRS) at 1 year as well as a sustained increase in quality of life after implantation were reported (P4-072).

April 24, 2018

  • BIIB054, an alpha-synuclein antibody in development at Biogen, is under investigation to see if it can interfere with alpha-synuclein aggregation and thereby improve the underlying pathology of Parkinson’s disease and slow down the course of the disease. It was tested in 18 patients with Parkinson’s disease and was shown to be safe and well tolerated. Complexes of BIIB054 bound to alpha-synuclein were found in patients’ blood. A phase 2 study to test this antibody in larger numbers of patients is now underway (S26-001)
  • The International Stem Cell Corporation presented data on their neural stem cells, derived in a unique manner, from an unfertilized human ovum. An open label study was conducted in which these cells were injected into 12 PD patients. So far, this strategy has proven to be well tolerated and safe. Development of a method of successfully replacing lost cells in Parkinson’s disease has been very difficult for scientists so far, and any step in the right direction is welcome (S26-002).
  • Results of a number of trials, supported by Acorda, using inhaled Levodopa (CVT-301) to treat OFF time were presented. The trials showed improvements in patients’ motor scores as well as improvements in patient-reported OFF time. (S26-004, S26-005, S26-008).
  • PD patients were able to increase their own brain activity as assessed by functional MRI, using neurofeedback techniques. Much research remains to be done, most importantly as to whether the increase in brain activity had any clinical effects on patients. However, this preliminary data suggests that neurofeedback could turn out to be a powerful tool to help a PD brain (P3-075).
  • Results of the INTREPID trial were presented at the Emerging Science abstract session. INTREPID is a double blinded, multi-center randomized controlled trial evaluating the VERCISETM deep brain stimulation system manufactured by Boston Scientific. The new system is unique in that it allows physicians to independently control the amount of current delivered by each of the eight electrodes on the implanted leads. (Emerging Science platform session-001).

April 23, 2018

  • A STEADY-PD III trial update was presented. This study is investigating whether a medication already approved for high blood pressure, isradipine, acts as a disease modifying therapy in patients with Parkinson’s disease. A disease modifying therapy is one that can slow down the course of the disease. The study has closed to enrollment and the last patients will complete the study in November 2018. After that, further data analysis will look at many variables including whether or not taking isradipine for three years delayed the need to start on levodopa or changed a patient’s levodopa requirement. Identifying a therapy that can slow down PD would be a huge win for the PD community (P2-039).
  • An update of the drug metabolism profile and safety of the Carbidopa/Levodopa Accordion Pill was presented by Intec Pharma, Inc. This pill is designed to slowly unfurl in the stomach over time, allowing for slow release of the medication. The hope is that this pill design will allow for the effects of Carbidopa/Levodopa to last longer. This medication is currently in phase 3 clinical trials in the US (P2-040).
  • An update of the iNDiGO study was presented. This study is investigating another new delivery system of Carbidopa/Levodopa, a subcutaneous infusion (currently known as ND0612). Study recruitment is ongoing. The hope is that this new delivery system which provides for continuous infusion of Levodopa under the skin, will decrease OFF time (P2-044). Encouraging results of a small open label study involving 38 patients will be presented on April 24th (S26-003)
  • A Parkinson’s specific electronic medical record order set was created at Northwestern Memorial Hospital in Chicago. This system was designed to try to reduce medical errors in hospitalized patients with Parkinson’s disease, enabling accurate medication dosing and timing (P2-077).

April 22, 2018

  • The tears of people with Parkinson’s disease have a different protein composition as compared to the tears of people without PD. In a small study, the tears of people with PD contained significantly less total alpha-synuclein, but more of particular forms of alpha-synuclein than control tears. If this can be replicated in larger studies, testing tears could be a way to diagnose Parkinson’s disease in the future (S3-006)
  • Wearable sensors were able to distinguish between a patient’s ON and OFF state. This type of technology could substantially improve data collection on whether a trial drug is effective, instead of the current method of relying on patient diaries to report ON and OFF time. (S3-007)
  • Glucose control was impaired in advanced PD patients without diabetes as compared to people without PD. Since insulin secretion is controlled by the autonomic nervous system, poor glucose control may be a previously unrecognized non-motor symptom of PD. (S3-008)
  • Nilotinib is a chemotherapeutic agent, used mostly to treat patients with certain types of leukemia. In 2015, it was tested in PD patients in a small, open label study, with the theory that the drug could help clear alpha-synuclein deposition from neurons. This current study showed that nilotinib caused significant changes in the chemical makeup of the cerebral spinal fluid of the patients in the trial, demonstrating that nilotinib did in fact cross the blood brain barrier. (S3-005)

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