Two potential Parkinson's disease therapies progress through clinical trials

Two investigational Parkinson's disease therapeutics – a stem cell-based therapy and a gene therapy – have both advanced into late clinical development.

The first patient has been dosed in a phase III clinical trial of bemdaneprocel, which is the first investigational allogeneic pluripotent stem cell-based therapy for Parkinson's disease to progress into the third phase of clinical development. Simultaneously, an investigational gene therapy for Parkinson's disease – AB-1005 – has entered phase II clinical development in Europe. Both trials aim to assess the safety and efficacy of the therapies as well as their broader clinical outcomes.

'Our dual approach in addressing Parkinson's disease through both cell and gene therapies exemplifies our strategic vision and maximises our chances of offering renewed hope for Parkinson's patients who have been waiting for new therapies for too long,' said Dr Christian Rommel, global head of research and development at Bayer Pharmaceuticals.

Parkinson's disease patients typically present with motor symptoms – including tremors, muscle stiffness and slowness of movement – which are driven by the loss of nerve cells (neurons) that produce a chemical called dopamine. Dopamine helps control body movement.

Bemdaneprocel is a cell therapy that was initially developed by Memorial Sloan Kettering Cancer Centre, New York, before being licensed to BlueRock Therapeutics, an independent subsidiary of Bayer. The therapy is composed of human embryonic stem cells that are programmed to develop into early forms of dopamine-producing neurons when transplanted into both sides of the putamen within a Parkinson's disease patient's brain. The putamen is critically involved in motor control. Results from a phase I clinical trial earlier this year reported that the transplanted cells produced dopamine with no serious side effects (see BioNews 1258).

The trial, across seven sites in the USA, is designed to recruit approximately 100 patients with Parkinson's disease, who will be randomised to receive either the cell therapy or a sham surgery to exclude potential placebo effects. In addition to assessing the safety and efficacy of bemdaneprocel, the researchers also plan to investigate the effects of the treatment on clinical outcomes such as the patient's movement, quality of life and the drug's impact on the patient's daily life.

AB-1005 is a gene therapy that was initially developed by University of California, San Francisco, before being licensed to AskBio, which is also an independent subsidiary of Bayer. The therapy was designed to increase the levels of a protein called glial cell line-derived neurotrophic factor (GDNF), which is known to play a role in protecting and regenerating dopaminergic neurons. AB-1005 is composed of an adeno-associated virus (AAV) vector containing a GDNF transgene, which is directly injected into both sides of the putamen within a Parkinson's disease patient's brain, with the aim to help protect or restore dopamine-producing neurons affected by the disease.

Results from an initial phase Ib clinical trial were published in Movement Disorders earlier this year, indicating that the gene therapy was well tolerated. Now, the phase II trial is designed to recruit approximately 87 patients with Parkinson's disease in Germany, Poland, the UK and the USA. The participants will be randomised to receive either the gene therapy or a sham injection. Similarly to the cell therapy, the researchers will assess the safety, efficacy and clinical outcomes of the gene therapy.

'The need for disease-modifying therapies is one of the greatest unmet needs in this area,' Christie Wong, neurology expert at market researcher GlobalData, who is not involved in the trials, told Reuters.

Bayer has acknowledged that both therapies are still in clinical development and have not yet been approved for use in clinical settings.