It has been more than 200 years since British doctor James Parkinson first identified the symptoms of a condition that he termed shaking palsy; unfortunately, there is still no cure to the disease that carries his name. His birthdate of April 11 has been designated World Parkinson's Day and aims to raise awareness about the disease, which has become the second most common age-related neurodegenerative disorder after Alzheimer’s disease, and is estimated to afflict more than 6 million people worldwide. While drugs are available to treat the motor symptoms of Parkinson’s disease (PD), therapeutics to treat the underlying pathological or genetic mechanisms of the condition remain a work in progress.

SVB Leerink’s Marc Goodman noted that disease-modifying therapies (DMTs) are the holy grail for treating PD in a report identifying some of the key industry themes from the Advances in Alzheimer’s and Parkinson’s Therapies (AAT-AD/PD) focus virtual meeting.

Targeting alpha-syn

One of the primary targets that companies are now zeroing in on is alpha-synuclein, since research has indicated the disease is precipitated by a substantial loss of dopaminergic neurons in the brain accompanied by accumulations of filamentous protein inclusions predominantly composed of alpha-synuclein (aSyn). Misfolding of the aSyn protein causes inflammation, synaptic dysfunction and ultimately neuronal cell death.

Monoclonal antibodies against alpha-synuclein are being used to reduce concentrations of the protein and to prevent cell-to-cell transmission of pathological alpha-synuclein. For example, at the online AAT-AD/PD meeting, AC Immune SA, of Lausanne, Switzerland, described the development of antibodies with high affinity for aggregated alpha-synuclein, which prevent the intercellular spreading of toxic alpha-synuclein species. Data demonstrate that lead candidate antibodies reduce the de novo formation of alpha-synuclein aggregates in vitro and significantly decrease spreading of alpha-synuclein pathology in a mouse model of human disease. A lead therapeutic candidate has been advanced into preclinical development to treat Parkinson’s disease and other synucleinopathies.

There are also antibodies that have reached clinical testing. Biogen Inc.’s cinpanemab (BIIB-054), an anti-alpha-synuclein antibody, is currently in a phase II study with results expected in the second half of this year. Prasinezumab (PRX-002/RG-7935) is an investigational monoclonal antibody that targets alpha-synuclein, which is being developed through a worldwide collaboration with Roche Holding AG. The pharma is conducting a phase II study. Astrazeneca plc and Takeda Pharmaceutical Co. Ltd. are co-developing alpha-synuclein-targeting antibody MEDI-1341 (TAK-341), which is in a phase I study. The crowded field also includes Abbvie Inc.’s ABBV-0805, also in a phase I trial.

Gene therapy emerging

Gene therapy is emerging as a promising approach for treating neurological disorders, including Parkinson’s disease. The gene responsible for amino acid decarboxylase (AADC), the enzyme that converts levodopa into dopamine, is a target for therapies.

For example, among the companies involved in that research area, Voyager Therapeutics Inc. is working with Neurocrine Biosciences Inc. on four experimental AAV-based gene therapies, the most advanced of which is VY-AADC, a gene therapy candidate designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located. Unfortunately, their RESTORE-1 trial of VY-AADC (NBIb-1817) has temporarily paused screening of new patients to allow clinical trial sites to assess the impact of the COVID-19 pandemic on both the implementation of previously disclosed protocol amendments and on the safety of study participants. The companies plan to resume patient screening and enrollment as soon as the assessment is completed and once the environment allows. The companies said they continue preparations for the initiation of the RESTORE-2 registrational study in Parkinson’s disease planned for the second half of this year.

Seelos Therapeutics Inc., of New York, has licensed a preclinical gene therapy program targeting the regulation of the SNCA gene, which encodes alpha-synuclein expression, from Duke University. It will initially study the program, which it named SLS-004, in Parkinson's disease. SLS-004 is an all-in-one lentiviral vector for targeted DNA-methylation editing within intron 1, the company said. In March, the company generated $4.5 million from an underwritten public offering to support its clinical programs.


Both public and private companies involved in developing therapies targeting Parkinson’s disease have been successful in attracting financing. According to BioWorld data, approximately $850 million was invested last year and almost $2 billion in 2018.

Prevail Therapeutics Inc., of New York, for example, raised $125 million from an IPO last year. The company is developing a portfolio of novel AAV9-based gene therapy candidates for neurodegenerative diseases. It said it would use as much as $60 million to advance development of its lead candidate, PR-001, for the treatment of Parkinson's disease with GBA1 mutation (PD-GBA). The company has initiated dosing in a PROPEL phase I/II trial of PR-001 for patients with PD-GBA.

Aspen Neuroscience Inc. launched in December following a $6.5 million seed round to develop the first autologous cell therapies for Parkinson's disease. Its research is focused on induced pluripotent stem cells (iPSCs), which it develops using a skin biopsy taken from a person with PD.

Lead product ANPD-001 is undergoing investigational new drug-enabling studies for the treatment of sporadic Parkinson's disease. Aspen is also developing a gene-edited autologous neuron therapy (ANPD-002) that is in the research stage and targeted toward familial forms of Parkinson's disease, beginning with machine-learning tools and artificial intelligence to ensure quality control during manufacturing and to deliver a safe and reproducible product for each cell line. In April, San Diego-based Aspen closed a series A funding round of $70 million.

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