Researchers Are Getting Closer To A Drug That Is Truly A Parkinsons Treatmentone That Can Halt Or Cure The Disease Instead Of Just Fighting Symptoms
As the incidence of Parkinsons growsan estimated 50,000 new cases per yearso do the options being offered by drug manufacturers.
Todays Parkinsons treatment options address the symptoms of tremors, stiffness, and slow movement to improve quality of life. However, they do little to slow the progression of this disease. Fortunately, research is helping us better understand Parkinsons. While early signs of Parkinsons disease can be overlooked, once its diagnosed, treatment options are expanding beyond the current drugs. So one day we may find a Parkinsons treatment that makes the disease less of a life sentence.
If you have Parkinsons disease, there arent any treatments that can slow, reverse, or stop the conditions progression, says Kara J. Wyant, M.D., in a Michigan Health blog on Parkinsons treatment. But, although there is no cure, more than a dozen medications can help patients manage symptoms. Our goals when prescribing medications for Parkinsons disease are twofold: to improve day-to-day functioning and quality of life and to keep people functioning as long as possible.
Where Is Drug Development Headed
Overall, experts say the Parkinson’s disease field aims to develop therapies that can slow or stop disease progression. Kordower notes several promising gene therapy and stem cell therapy approaches are entering the early stages of clinical development.
Most ongoing PD trials are at the Phase II stage, according to GlobalDatas Clinical Trial Database. While institutions are sponsoring 84 trials of the 133 ongoing Phase II studies , pharma companies are running 44 trials of the 56 ongoing Phase I studies .
As the field awaits results from the slew of ongoing trials, experts agree that the PD trials reading out in the remainder of 2022 could have a substantial impact. These four trials are all very timely, Eidelberg says. The community of movement disorder specialists and neurologists would use these drugs because the indications we’re talking about are really very common.
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Progression Of Parkinsons Disease
The disease progression of PD from diagnosis has been conceptualised into four stages . It is also important to recognise a prodromal phase in which non-motor symptoms, such as anosmia, constipation and rapid-eye-movement sleep behaviour disorder may predict the development of motor PD. Motor complications are more common as PD progresses, and typify transition to the complex phase. Many so-called axial symptoms of later stage PD, such as dysphagia, gait disturbance and falls, do not respond to levodopa, but may be helped by multidisciplinary team input. Dementia occurs in up to 80% of people with PD after 20 years disease duration. The rate of PD progression is heterogeneous and is generally more rapid in those with older age and more severe motor impairment at onset.
Stages of Parkinsons disease. RBD = rapid eye movement sleep behaviour disorder.
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Stay Safe With Your Medicines
Read all labels carefully.
- Tell all your health care providers about all the medicines and supplements you take.
- Know all the medicines and foods youâre allergic to.
- Review any side effects your medicines can cause. Most reactions will happen when you start taking something, but thatâs not always the case. Some reactions may be delayed or may happen when you add a drug to your treatment. Call your doctor right away about anything unusual.
- Use one pharmacy if possible. Try to fill all your prescriptions at the same location, so the pharmacist can watch for drugs that might interact with each other.
- You can use online tools to see if any of your medicines wonât work well together.
You have the right and responsibility to know what medications your doctor prescribes. The more you know about them and how they work, the easier it will be for you to control your symptoms. You and your doctor can work together to create and change a medication plan. Make sure that you understand and share the same treatment goals. Talk about what you should expect from medications so that you can know if your treatment plan is working.
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How Could Stem Cells Help People With Parkinson’s
Stem cells are the parent cells of all tissues in the body. This means they can turn into any type of cell. The hope is that they will eventually be able to make these cells into specific types of cells, like dopamine-producing neurons, that can be used to treat Parkinson’s disease. However, there are concerns that patients may have the same risk of increased involuntary movements as those who undergo fetal cell transplantation. And, like fetal cell transplantation, stem cell therapy is surrounded by moral and ethical controversy.
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Opportunities For Input From Pharmacy Professionals
As there is no cure for PD, medication management is crucial in managing the disease. Pharmacy professionals can play a significant role in both primary and secondary care. It is important that pharmacy professionals are familiar with PD symptoms and are aware of which referral pathway is most suitable for the patient. Many of the symptoms are straightforward to manage for example, constipation, and simple interventions can make a big difference to the patients quality of life.
Pharmacy professionals should also be aware of local services that are available to both patients and themselves. The Parkinsons UK website provides support and resources for healthcare professionals, patients and their family or carers.
Parkinsons Articles And Podcasts
- A study published in the journal Brain shows that dopamine systems are affected differently in people with Parkinsons with tremor compared to people without tremor and that this affects cognition as well as motor symptoms. Researchers who explored whether the presence of tremor was associated with levodopas effect on reinforcement learning found that people treated with levodopa who did not have tremor had better reinforced learning skills than did those with tremor, who did better at avoidance learning .
- A recent When Life Gives You Parkinsons podcast episode explores how people with Parkinsons can be their own best advocates.
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The Impact Of Remotely Supervised Tdcs On Parkinsons Disease And Other Neurological Conditions
NYU Langone researchers are also looking into the benefits of RS-tDCS for other neurological conditions in several open-label studies.
A study conducted in collaboration with researchers at the , slated for publication in the Journal of NeuroEngineering and Rehabilitation, demonstrated the applicability of this methodology in Parkinsons disease, with improvements in fatigue and cognition similar to those seen in MS. Further, as published in 2018 in the Journal of Clinical Neuroscience, patients with moderate Parkinsons disease experienced a notable reduction in symptoms from using RS-tDCS in combination with cognitive training.
The use of telemedicine to supervise at-home tDCS will allow us to reach more patients and also to bypass common obstacles that prevent populations with mobility impairment or other accessibility barriers from participating in clinical trials and receiving health services, says Milton C. Biagioni, MD, assistant professor of neurology and coinvestigator on the study. This is the first time an RS-tDCS protocol has been designed for and tested in these patients.
According to study coinvestigator Milton C. Biagioni, MD, telemedicine allows people who have mobility impairments to access healthcare services and clinical trials.
Although studies currently focus on patients with moderate Parkinsons disease, researchers at the Fresco Institute anticipate expanding these investigations in the near future to include patients with advanced disease.
Radical New Therapy For Parkinsons Will Use Stem Cell Transplants
Lab-grown nerve cells will replace those destroyed by disease scientists hope treatment may be available in five years
Early next year, a radical new treatment for Parkinsons disease involving tissue transplants will receive its first trial with patients including a group from the UK.
Stem cells grown in the laboratory and transformed into nerve cells will be used to replace those destroyed by the disease. It is hoped that these will stop the spread of debilitating symptoms.
It has taken a long time to get to this stage but hopefully results from these trials will mean that, in a few years, we might be able to offer tissue transplants as standard treatments for Parkinsons, said Prof Roger Barker, of Cambridge University. It is certainly a promising approach.
In the UK, about 145,000 people live with Parkinsons and about 18,000 new cases are diagnosed every year. The disease is triggered when nerve cells that supply dopamine to the brain start to die due to a combination of genetic and environmental factors.
Dopamine helps a person control movement. When supplies drop, the result is shaking, stiffness, depression and other symptoms that can end with patients using a wheelchair or being bed-ridden. The diseases progress can be slowed by the drug L-dopa, which replaces some of the lost function of dopamine cells. Treatments become less effective over the years. Scientists have been searching for years for new approaches.
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New Medications For Off Time
A number of new medications approved recently are designed to reduce OFF time. These medications fall into two major categories:
- Medications that lengthen the effect of a carbidopa/levodopa dose
- Medications that are used as needed if medication effects wear off
Well give specific examples below. In general, new medications that extend the length of a carbidopa/levodopa dose are used if OFF time is somewhat predictable and occurs prior to next dose. New medications that are used as needed are most beneficial when OFF time is not predictable.
New medications that lengthen the effect of a dose of carbidopa/levodopa
Previous restrictions on the intake of foods containing tyramine with selective MAO-B inhibitors have been relaxed by the Food and Drug Administration . However, MAO-B inhibitors can interact with other medications, such as certain antidepressants, nasal decongestants, and narcotic pain medications. Typically, if a person is undergoing a procedure in the hospital and is taking a selective MAO-B inhibitor, they are advised to stop the medication two weeks prior to the procedure and to restart it 1-2 weeks after the procedure to avoid any unintentional medication interactions.
New formulations of levodopa designed to be used as needed if medication effects wear off
Other medications used as needed if medication effects wear off
Parkinsons Disease: Major Drug Trial Results To Watch In 2022
Four clinical trials in Parkinsons disease with readouts the second half of 2022 target motor symptom fluctuations and cognitive impairment.
In a slate of major Parkinsons disease trial readouts, drug developers are taking aim at the diseases most common symptom: motor fluctuations.
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Test Can Accurately Predict Who Currents Has Ad And Who May Develop It Later
According to researchers, the early seeds in the brain that later grow into Alzheimers disease are called amyloid beta proteins. Instead of behaving like healthy proteins in the brain, these amyloid beta proteins misfold and clump together, forming small masses called oligomers.
For reasons that are still not completely understood by scientists, the oligomers are thought to cause the damage that eventually results in Alzheimers.
Researchers found that SOBA could detect oligomers in the blood of patients with Alzheimers disease. In the control group, which only included people who showed no signs of cognitive impairment at the time their blood samples were taken, 11 people were found to have oligomers.
Ten of those people were able to be medically followed, and all were eventually diagnosed with mild cognitive impairment or brain pathology consistent with Alzheimers. The test had identified the at-risk individuals before the presence of any symptoms, and the blood samples from people who never went on to develop cognitive impairment lacked the toxic oligomers.
Mild cognitive impairment is an early stage of memory or cognitive ability loss. People with MCI are at a significantly increased risk of developing dementia, but some people with MCI remain stable for many years, per Mayo Clinic.
Advances In Deep Brain Stimulation
Deep brain stimulation is another established treatment for PD that is useful in treating dopamine-dependent motor symptoms when levodopa-induced side effects become particularly problematic. DBS involves the surgical implantation of electrodes that stimulate subcortical structures including the subthalamic nucleus and globus pallidus internus9194. DBS offers significant improvements in motor symptoms and fluctuations in comparison to best medical therapy in some advanced PD patients, but dopamine-resistant symptoms other than tremor respond poorly95. It has also been suggested in an open-label trial that DBS is beneficial in early PD patients, with improved tremor scores and reduced development ofde novo tremor96. In addition to surgical complications, DBS strategies may cause cognitive and neuropsychiatric adverse effects as well as speech dysfunction. Novel DBS approaches, including adaptive DBS, targeting different regions, and refined intra-operative imaging techniques promise to offer improved clinical applicability and reduce the impact of adverse effects97.
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Parkinsons Disease: A Hopeful Future
Parkinsons disease is the fastest growing neurological condition in the world. Between 1990 and 2015, the number of people with this disease doubled to over 6 million . This number is predicted to double again to 12 million by 2040, primarily because of an ageing population . In the UK, the lifetime risk of developing Parkinsons disease is 2.7%, with approximately 17,300 new diagnoses made every year in people aged 45 and above .
Parkinsons disease is a progressive, neurodegenerative disorder of the brain . It is characterised by the death of certain brain cells , particularly in an area of the brain called the substantia nigra . A high proportion of neurons within this part of the brain use a chemical called dopamine to transmit signals between themselves and throughout the brain these signals act to coordinate movement .
As the neurons in the substantia nigra die off, the amount of dopamine falls, which results in some of the major features of Parkinsons disease, such as slowness and stiffness of movement .
Adapted from International Society for Stem Cell Research 2022.
These symptoms increase in severity over time as more neurons are lost, and eventually patients may experience a resting tremor and have problems walking . Approximately 80% of patients also develop dementia within 20 years of disease onset .
Current treatment options target the symptoms, but not the cause
A new era: Targets for the Parkinsons disease medication pipeline
Lewy body accumulation
Parkinsons Living Well Stories
- In a recent TODAY Sunday interview, Michael J. Fox shares details of the conversation he had with his wife, Tracy Pollan, when he told her about his Parkinsons diagnosis almost 30 years ago. One of the things Ill always love about Tracy for is that at that moment, she didnt blink.
- Veteran NASCAR driver and team owner Morgan Shepherd, who recently shared that he has been diagnosed with Parkinsons, is focusing on the positive and making plans for an inspired and successful 2021.
- At their TITLE Boxing Club in Florida, two veterans living with Parkinsons keep themselves and others motivated, reciting songs or answering trivia questions as they work out to strengthen their mind-body connection.
- Live well in 2021! Find holiday gifts for a loved one living with Parkinsons with ideas from Sherri Woodbridges A Gift Guide for Shopping from Home.
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Over The Counter & Complementary Therapies
People with Parkinsons who seek relief from their symptoms may decide to explore complementary therapies, which can support or complement traditional medicine. While there are many kinds of complementary medicine, this section focuses on herbs, vitamins and supplements.
Page reviewed by Dr. Chauncey Spears, Clinical Assistant Professor and Dr. Amelia Heston, Movement Disorders Fellow at the University of Michigan.
Studies Show Promising Results
“Considering the ability of MSCs to secrete neurotrophic factors, modulate inflammation, and possibly even act as mitochondria âdonorâ, it comes as no surprise that there is a lot of interest in the use of MSCs in the treatment of Parkinsons Disease, and a multitude of animal studies has shown promise. Treatments have resulted in improvement of motor function, protection of the nigrostriatal system, and improved striatal dopamine release in several studies using toxic lesion rodent models of Parkinsons Disease. Similar effects were reported with umbilical cord-derived MSCs with or without prior differentiation. For example, a recent study reported improvement of motor function, reduced microglial activation, and decreased loss of TH immunoreactivity, associated with local production of trophic factors.
Learn more about DVC Stem’s protocol for Parkinson’s Disease here:
References:
Venkataramana, N. K., Kumar, S. K. V., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., ⦠Totey, S. M. . Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Retrieved from https://www.sciencedirect.com/science/article/pii/S1931524409002205#!
Unified Parkinson’s Disease Rating Scale. . Retrieved from https://www.sciencedirect.com/topics/medicine-and-dentistry/unified-parkinsons-disease-rating-scale
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Amneal Tests A New Formulation
AmnealPharmaceuticals plans to report Phase III safety results for IPX-203, a reformulation of the common generic PD treatment combination of carbidopa and levodopa that could reduce symptom fluctuations. The company said the Phase III, open-label extension study will have results available by the end of the second quarter of 2022.
CD/LD can lead to troughs and spikes of plasma levels that generate side-effects like dyskinesia, Kordower explains. A new extended-release version of CD/LD could smooth out these drops, he notes.
If approved, IPX-203 will join several other marketed reformulations of CD/LD. Amneals own extended-release capsule Rytary, Schwarz Pharma s orally disintegrating tablet Parcopa, and AbbVie’s enteral suspension Duopa all have FDA approval in PD. A GlobalData consensus forecasts pegs peak IPX-203 sales at $127 million in 2028.
In a separate, placebo-controlled Phase III trial , IPX-203 resulted in 0.53 more hours of ON time than immediate-release CD/LD after seven weeks . Earlier, a six-week Phase II trial of IPX-203 reported no serious treatment-emergent adverse events among the 26 patients enrolled. Experts say the long-term safety data will be key in determining IPX-203s place among CD/LD formulations.