The Cure Parkinson's Trust is determined to facilitate research from concept to treatment and accelerating the regulatory process forms a part of this. This complex topic was discussed at our Medicine and Me patient conference in October 2008. Professor Alastair Breckbridge, Chairman of the MHRA ( Medicines and Healthcare products Regulatory Agency) was in attendance to answer questions from people with parkinson's on the MHRA process. Following a lively discussion at the meeting, this continues to be an area of interest and involvement for us.
Bringing new therapies to market is a complex process, the MHRA's brochure explains in more detail - Click here for the brochure.
You may also be interested to see the NICE ( National Institute for Health & Clinical Excellence) guidelines as these too have a major impact on what drugs are available to people with parkinson's. Click here for further details.
Over the past few months aspects surrounding the supplementary oral administration of Vitamin D for PD has generated interest within the PD community. The core rationale for this is summarised by Marion Evatt's 2008 report in Archives of Neurology which demonstrated that a significant proportion of PD patients had deficient plasma levels of Vitamin D. The sometimes-linked notion in the posts was that Vitamin D may possess a direct protective action on neurones.
The Cure Parkinsons Trust is also very interested, and active, in Vitamin D research. The fact that several diverse reports (Surmeier, Ritz, Rodnitzky and others) have shown calcium channel blockers offer very substantial protection against PD, and also that they provide phenomenal protection and reversal of symptoms in experimental models of PD (Surmeier), has led to the recent commencement of a major clinical trial in PD patients on the anti-hypertension therapy, Isradipine. This trial is scheduled to finish next Summer. There is good reason to speculate that low levels of vitamin D act more by interfering with normal calcium flux, than by any direct protective effect on neurones yet postulated. How perturbations in calcium flux may be relevant to PD was recently and excellently explored the Journal, Neuron (Mosharov, with a fine leader by Surmeier). A further relevant fact is that extracellular calcium receptors have been specifically detected in areas of the brain involved with PD, i.e. not just in the kidney and parathyroid (their logical homes).
You may be pleased to learn that, for quite some time now, the world's leading calcium channel blocker experts have been talking to the leading Vitamin D experts about PD. The Cure Parkinsons Trust is also playing its part here. We hope to announce before too long we are funding at least two new studies that we have helped design in these areas.
Later this year, we are also holding the first ever conference on the role of calcium (and Vitamin D) in PD where leading experts, including many of those mentioned above, will come together to discuss our current understanding, and to design onward collaborative studies involving all these research teams.
This November, The Cure Parkinsons Trust will be hosting a two day conference at the Royal Society of Medicine in London where leading scientists and clinicians from around the world will discuss the potential of using anti-inflammatory and anti-oxidative therapies to treat Parkinson’s Disease, and most especially, to slow its progression.
The past 2-3 years have seen enormous interest in this promising field of research, and several different drug and lifestyle nutritional approaches have emerged from it which offer both theoretical and tangible, now proven, benefits.
There is ample evidence that an inflammatory response occurs in brain cells in Parkinson’s Disease. Some scientists say it is a fundamental part of the disease process, others feel it is just a response to it. Whatever the truth, many agree that this inflammation increases local damage to brain cells, and therefore accelerates disease progression. Accordingly, many are interested in using some of the many different types of anti-inflammatory drugs to try to slow disease progression, and a variety of these are also being tested in laboratories and clinics around the world to try to achieve this goal. Other scientists concentrate on trying to understand and interfere with the uniqueness of the inflammatory response itself in brain cells (brain cells are specialized in this context, differing considerably from the inflammatory response in the rest of the body and therefore not quite equivalent to, say, a swollen knee, but perhaps similar in some respects).
Recent clinical studies have shown the blood level of urate, a powerful anti-oxidant, can influence the progression of Parkinson’s Disease by as much as 40%, even suggesting the possibility that dietary modification could soon become a standard part of treatment. Several other nutritional anti-oxidative and anti-inflammatory approaches with strong biochemical credentials, and associated drug options, also currently appear scientifically promising in our attempt to delay disease progression.
Some scientists believe an over-accumulation of a protein, alpha-synuclein, in brain cells in Parkinson’s Disease, creates a localized inflammatory stimulus at the elevated protein levels often associated with the disease. Until now, there were only some immature experimental ways to try to remove excess alpha-synuclein from brain cells but, within the past month, two exciting, quite different, breakthroughs potentially capable of limiting its actual build-up in cells have been reported.
Already financially supporting research in some of these areas, The Cure Parkinsons Trust anticipates the conference will provide a vivid 2-day interaction on these topics between world experts in this rapidly developing area of Parkinson’s research and treatment.
The Cure Parkinson’s Trust has been actively funding projects using neurotrophic factors and believes that these growth factors play a vital part in cell regeneration, and therefore potentially could help reverse the symptoms of Parkinson’s.
Growth factors (or neurotrophic factors) are proteins that promote the survival, growth and function of neurons in the brain. These proteins are of great interest to Parkinson’s researchers because the degeneration of dopamine neurons defines Parkinson’s disease. We are interested both in the growth factors themselves such as GDNF and Neurturin, and in drugs that influence how such factors are produced within the brain.
GDNF: We have been funding neurosurgeon Professor Steven Gill in Bristol for three years, who has been infusing GDNF directly into the brain where it is deficient in dopamine cells, with the aim of regrowing the cells that die off in Parkinson’s. Early studies show that GDNF has a positive effect on cell regrowth. Neurturin: We met the two major companies working with Neurturin and are exploring how best to further their research
Cogane: We have been funding Dr Jon Brotchie, who has been using Cogane, a plant derivative that has been identified by Phytopharm, and is thought to release GDNF into the brain, mimicking the effect of its direct injection. This is part of an attempt to move towards a more convenient oral treatment for millions of patients around the world. We are looking to support patient trials with Cogane later this year and believe that this is a very exciting and promising study. The Michael J Fox Foundation has just committed funds for further studies with Cogane, a good example of our funding generating significant further investment.
AS101: We are funding clinical and laboratory studies on a tellurium-based drug, which is thought to have the dual effect of protecting existing cells and stimulating the growth of new ones. Early feedback from the laboratory findings look extremely promising.
For cohesion and comprehensiveness of approach, we are also currently in active
discussions about assisting other groups around the world who are working in the
growth factor area in Parkinson’s, each from different perspectives.
The Cure Parkinson’s Trust’s Head of Research, Dr Richard Wyse, who is also head of the genetics section of the Royal Society of Medicine, is enthusiastic about a new Genetics study into Parkinson’s disease that has been funded by The Wellcome Foundation and is being carried out in the UK and USA simultaneously.
Our understanding of many diseases has been greatly enhanced by genetic discoveries since the human genome was mapped in 1994. Scientists discovered that the particular function of each type of specialised cell was defined by its genes, but modified by another molecule called RNA which produces proteins in the cell. This acts as the control system within the cells. Through studying our genes and RNA we have the opportunity to analyse the massive, but tiny cellular control system, and particularly how it is affected when diseased.
The Wellcome Foundation study into Parkinson’s is timely. Parkinson’s research is being hampered as there is no clear understanding of what causes patients to develop Parkinson’s. A genetic map for the disease will help this. Importantly, it is hoped that it will also help define appropriate treatments dependent on each person’s Parkinson’s.
For example, there are a small number of relatively young onset cases that are known to have inherited one of the half a dozen different genetic abnormalities, which directly cause the disease. These cases represent less than 10% of all Parkinson’s patients but they provide fascinating insights into the disease, and how to treat it.
In May a definitive study of 3,000 Parkinson’s patients started, which aims to determine the contribution of genetics to the development of the disease. Based on prior experience with similar approaches in other diseases, we anticipate about 100 genes will be identified that will be specifically related to Parkinson’s. Some will be critical to the development of the disease, some will be involved in the body’s response to the disease, and some involved in how natural chemical signals, and pharmaceutical chemical signals, in the body act.