The Swedish Medical Products Agency has approved an application from a consortium of research institutions, which includes Lund University, to initiate a clinical phase I and a phase IIa study in Parkinsons disease, STEM-PD. The aim is to investigate whether transplanted nerve cells, which form dopamine and are generated from embryonic stem cells, can replace the nerve cells that are destroyed at disease onset. Thus begins another clinical trial in this neurodegenerative chronic disease that, after 105 years after its discovery, still lacks curative treatments.
Parkinson’s disease, a progressive neurological disease characterised primarily by a symptom combination of slowness of movements, tremors, stiffness and difficulty walking, is the second most common neurodegenerative disease in the world. The exact causes are still unknown, but the main hallmark of disease pathology is a progressive loss of the neurotransmitter dopamine in nerve cells of the midbrain.
Current treatments for Parkinson’s disease replace dopamine with symptom-relieving medication. The drugs are effective, especially in the first years after diagnosis, but the treatments are limited by the worsening of the disease and with increasing side effects of the medications. The development of regenerative cell therapies with the aim of replacing the loss of dopamine nerve cells at the site where they act in the brain’s motor system, would represent a major advancement in the treatment of Parkinson’s disease, and could reverse the course of the disease.
An incurable disease
The symptoms, which worsen over time, can be treated quite effectively today, and for many years. This is usually done by supplying drugs that are converted into dopamine in the affected areas of the brain. However, the effect becomes difficult to sustain after a long period of treatment, which creates unnecessary suffering in the form of cognitive impairment, psychological disorders and pain. Therefore, the need for new treatment options is still great.
Stem cell-based therapy
Research groups from Swedish Skåne University Hospital, University of Cambridge, Cambridge University Hospitals NHS Foundation Trust (CUH) and Imperial College in London, led by Swedish Lund University, have now been given the green light to start a new phase I/II study with a stem cell therapy. This therapy, which is based on a collaboration and scientific studies that have been going on for many years, goes by the name STEM-PD.
The aim is to investigate whether transplanted dopamine-forming neurons generated from embryonic stem cells, can form new functional dopamine neurons in the patient’s brain after transplantation, with the aim of replacing the nerve cells lost during the course of the disease with new, healthy neurons, thus restoring dopamine levels in the brain. Both preclinical and clinical research have received financial support from, among others, Scandinavia’s largest pharmaceutical company Novo Nordisk, with whom the research groups also collaborate on future product development.
This first-in-human clinical trial, which includes up to eight patients for transplantation, can be formally initiated after approved inspection by the Swedish Medical Products Agency. It is not possible to volunteer to participate in the trial.
Safety and tolerability to be investigated
To date, preclinical data suggest that the STEM-PD product meets safety requirements and is highly effective in restoring motor impairments in preclinical models of Parkinson’s disease.
The primary endpoint in the study is to assess the safety, tolerability and feasibility of transplantation of stem cell-derived dopamine cells to the brain in patients with moderate Parkinson’s disease. The secondary endpoint is to investigate clinical effects 36 months after transplantation, and to investigate whether the cells survive using the imaging technique PET and MRI. Patients are then followed for life.
A pioneering effort
Skåne University Hospital is the clinical sponsor of the study, and it is also here that the transplant surgery will be carried out. The hospital has previously conducted cell transplants in clinical trials of Parkinson’s disease. However, the surgical procedures that will now be carried out at Skåne University Hospital in Region Skåne will be the first surgical transplant procedures with the new product of stem cell-derived dopamine cells.
The clinical development of the project is led by researchers at the University of Cambridge and Cambridge University Hospitals (CUH). The use of stem cells could, in theory, make it possible to produce unlimited amounts of dopamine nerve cells, thereby opening the possibility of making this promising therapy available to a wider group of patients. In the long run, there is thus an opportunity to fundamentally change the treatment of Parkinson’s disease, even if the researchers are still in the early stages of development.
Read more about the study here.