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Top 10 Parkinson’s Stories of 2018

Top 10, Parkinson's

Parkinson’s News Today provided you with daily coverage of important findings, treatment developments, and clinical trials related to Parkinson’s during 2018.

We look forward to bringing more news to Parkinson’s patients, as well as their family members and caregivers, during 2019.

Here are the Top 10 most-read articles of 2018, with a brief description of what made them interesting to the Parkinson’s community.

 No. 10 – “Phase 2 Trial Shows Nilotinib Potential to Modulate Dopamine in Parkinson’s

Results of a Phase 2 trial (NCT02954978) of Novartis’ nilotinib in 75 patients with mid-stage Parkinson’s and mild cognitive impairment suggested the therapy increased production and metabolism of dopamine within one to four hours after a single treatment. Also, low-dose nilotinib (150 mg and 200 mg) — marketed as Tasigna for certain types of leukemia — was associated with lower levels of an altered and toxic form of alpha-synuclein, the main component of Parkinson’s hallmark protein clumps known as Lewy bodies.

No. 9 – “Potential Parkinson’s Vaccine, Affitope PD01A, Safe and Possibly Effective in Long-term, Phase 1 Trial Series Finds

The long-term safety, tolerability, and immune response associated with an experimental vaccine called Affitope PD01A were studied in a series of four consecutive Phase 1 trials: AFF008 (NCT01568099), AFF008E (NCT01885494), AFF008A (NCT02216188), and AFF008AA (NCT02618941). Twenty-one treated and five control patients completed the series. The results showed that both 15 μg or 75 μg doses of Affitope were well-tolerated, only causing mild injection-site reactions. The vaccine, being developed by Affiris, induced a clear immune response against its target — alpha-synuclein — that was stabilized with “boost” injections. At week 26 of treatment, it induced a trend toward lower levels of a toxic form of alpha-synuclein in the blood and cerebrospinal fluid, the liquid surrounding the brain and the spinal cord.

No.8 – “MRI-Focused Ultrasound Undergoing Phase 3 Clinical Trial for Parkinson’s Treatment

A Phase 3 trial (NCT03319485) of a potential nonsurgical treatment, known as magnetic resonance imaging (MRI)-guided focused ultrasound, also attracted significant interest. The InSightec-sponsored study — still recruiting patients with advanced disease — is exploring the procedure’s safety and effectiveness. It follows a pilot trial demonstrating lesser upper-limb tremors in patients with tremor-dominant Parkinson’s who did not respond to other therapies. In this non-invasive approach, ultrasound waves destroy damaged tissue in a brain structure called the globus pallidus, which is involved in the regulation of voluntary movement. The team expects to enroll 80 to 100 participants.

No. 7 – “Key to Effective Parkinson’s Treatment May Lie in Stem Cells, Researchers Say

Advancements in stem cell therapy for Parkinson’s were also of clear interest to our readers. Two articles assessed the replacement of dopamine-producing neurons, progressively lost during the course of disease. The first focused on patient-derived induced pluripotent stem cells (iPSCs), fully matured cells that researchers are able to reprogram in vitro (in the laboratory) to revert them to a stem cell state in which they are able to grow into any type of cell, including dopaminergic nerve cells. The second study focused on an alternative approach to stem cell therapy that, instead of iPSCs, uses parthenogenetic-derived neural stem cells. These cells are obtained by chemical manipulations in unfertilized human oocytes, or immature egg cells, which are also able to grow into neurons. A Phase 1 trial (NCT02452723) of this approach is underway in patients with moderate to severe disease at a single site in Australia.

No. 6  “Psychosis in Parkinson’s Linked to Volume Changes in Specific Area of Brain, Study Says

Atrophy, or shrinkage, of the hippocampus — a critical brain area involved in memory — correlates with psychosis in patients with Parkinson’s disease. Specifically, researchers found that the volume of distinct subzones of the hippocampus was associated with psychosis severity and impaired cognitive functions. Greater volume was also seen in another specific brain area, the hippocampal fissure, and seems to correlate with poorer visual memory and visuospatial functions. Previous data had suggested that change in this area is a radiological hallmark of ongoing brain atrophy in the hippocampus.

No. 5 – Tiny Brain Bleeds Associated with Parkinson’s Disease Dementia, Study Reports

The link between tiny bleeds in the brain — cerebral microbleeds (CBMs) — with both cognitive impairment in Parkinson’s disease and risk of associated dementia was No. 5 among the year’s most-read stories. CBMs are small (2-10 mm as assessed by MRI), chronic brain hemorrhages believed to be caused by structural abnormalities of the brain’s small vessels. Scientists found that CBMs were more common in Parkinson’s patients with dementia than in those without dementia, and were associated with lower cognitive scores. Other findings showed that patients with CBMs were older, and had more severe Parkinson’s symptoms and cerebrovascular lesions.

No. 4 – “Vitamin B12 Supplements May Help Slow Parkinson’s Progression, Study Finds

Patients at early stages of Parkinson’s with low levels of vitamin B12 may experience faster motor and cognitive decline. Prior work had shown that B12 deficiencies can induce neurological and motor symptoms associated with Parkinson’s, including depression, paranoia, muscular numbness, and weakness. This study differed in that it was conducted in untreated patients earlier in the disease course, and found slower progression in those taking a multivitamin supplement. Overall, the findings suggest that vitamin supplements may help slow symptom progression.

No. 3  “Xadago, Cannabinoids, Opioids May Be Best to Manage Parkinson’s Pain, Review Suggest

Pain is a frequent non-motor symptom of Parkinson’s disease. A review study found that its management may be most effective with Xadago (safinamide, by US WorldMeds) or with cannabinoids and opioids.  Other approaches, such as multidisciplinary team care, Comtan (entacapone) and Tasmar (tolcapone) may also provide pain relief. In turn, the investigational treatment pardoprunox (SLV-308) and surgery reported only moderate benefits on reducing pain severity.

No. 2 – “Medical Cannabis Helps Older People with Parkinson’s, Other Diseases, Study Finds

Medical cannabis is a safe and effective option to ease pain in older patients with Parkinson’s, cancer, or other illnesses. In a study involving 2,736 people 65  years or older, its use over six months enabled a reduction or discontinuation of opioid pain medications in over 18% of patients. Participants also reported an improved quality of life. The most common adverse events were dizziness and dry mouth, reported by 7.1% of patients.

No. 1 – “Vitamin B3 Compound May Prevent Motor Decline in Parkinson’s Disease, Study Says

Out most widely read article of 2018 reported that a form of vitamin B3 — nicotinamide riboside — prevented the loss of motor function and lessened nerve cell death in a fly model of Parkinson’s. It also increased the levels of a metabolic compound called NAD+ and improved energy balance in fish neurons with a defective GBA gene — the most frequent gene risk for Parkinson’s — and defects in mitochondria, the cell’s powerhouse. The researchers suggested that this form of vitamin B3 may help treat impaired mitochondria function, which has been linked to Parkinson’s development.

 

At Parkinson’s News Today, we hope that these articles,  along our continuing reporting throughout 2019, help to educate, inform, and improve the lives of patients and their loved ones.

We wish all our readers a happy 2019.

 

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Nicotinamide Exacerbates Motor Symptoms of Parkinson’s Disease in Mice

Nicotinamide motor symptoms

A form of vitamin B3 can promote degeneration of nerve cells linked to Parkinson’s disease and exacerbate disease manifestations in mice, a study reveals.

Despite the benefits of the compound demonstrated in previous studies, these new contrasting findings suggest that its mechanism of action is complex and not specific for therapeutic effectiveness in Parkinson’s disease.

The study, “The Histone Deacetylase Inhibitor Nicotinamide Exacerbates Neurodegeneration in the Lactacystin Rat Model of Parkinson’s Disease” was published in the Journal of Neurochemistry.

Nicotinamide, also known as niacinamide or nicotinic amide, is a derivate of vitamin B3 found in various foods including beef, chicken, pork, fish, peanuts, and mushrooms, among others.

It is the precursor of an important metabolic compound called NAD+ that is essential for cells to produce the energy they need to function normally. Besides this, nicotinamide also is known to act as an inhibitor of enzymes called HDACs. These enzymes are responsible for regulating the genes that are available to produce active proteins and those that are silenced and inactive, through a process called epigenetics.

In Parkinson’s, both cellular energy production mechanisms and epigenetic processes are deregulated. Given that, nicotinamide could hold therapeutic potential for this disease by providing dual-protective activity.

A previous study has shown that treatment with nicotinamide could improve energy production by supporting the formation of new mitochondria — small cellular organelles that provide energy and are known as cells’ “powerhouses.” The study also showed that the treatment could prevent the loss of motor function in a fly model of Parkinson’s disease.

To further explore nicotinamide’s potential, researchers treated rats with induced Parkinson’s disease for 28 days. The disease was chemically induced by injection of lactacystin in one side of the substantia nigra — the brain area affected most by the disease — promoting the accumulation of altered and toxic proteins, mimicking what occurs in human disease.

Contrary to what researchers expected, nicotinamide treatment enhanced the death of brain cells and structural brain changes. Also, animals treated with a nicotinamide showed increased rate of motor decline and development of behavioral deficits compared to untreated animals.

Despite these negative effects, analysis of the genetic landscape of these animals’ brain tissue revealed that nicotinamide treatment increased the expression of several neuroprotective genes. However, this potentially positive effect failed to increase neuroprotection; rather, it exacerbated neurodegeneration. (Gene expression is the process by which information in a gene is synthesized to create a working product, like a protein.)

“These findings highlight the importance of inhibitor specificity” to achieve therapeutic effectiveness in Parkinson’s disease, researchers wrote.

In addition, the team believes these results demonstrate “the contrasting effects” of nicotinamide in cell survival in different animal models of the disease.

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Vitamin B3 Compound May Prevent Motor Decline in Parkinson’s Disease, Study Says

vitamin B3 nicotinamide riboside

A form of vitamin B3 can prevent degeneration and death of nerve cells linked to Parkinson’s and other neurodegenerative diseases.

The study with that finding, “The NAD+ precursor, nicotinamide riboside, rescues mitochondrial defects and neuronal loss in iPSC and fly models of Parkinson’s disease,” was published in Cell Reports.

It was shown recently that defective mitochondria are responsible for the death of dopaminergic neurons in the substantia nigra, a brain region particularly affected in Parkinson’s disease.

Mitochondria — tiny structures located inside cells that function as their powerhouse — produce the energy necessary for cell survival and function. However, their role in Parkinson’s is still controversial as alternative lines of research have suggested that mitochondrial defects may actually protect the brain by preventing the formation of protein aggregates.

“In our study we aimed to investigate whether damaged mitochondria were merely a side effect or whether they cause Parkinson’s disease,” Michela Deleidi, MD, said in a press release. Deleidi is a researcher at the German Center for Neurodegenerative Diseases and the University of Tübingen, and senior author of the study.

The team collected skin cell samples from Parkinson’s patients. They then converted skin cells into stem cells — which can give rise to almost any type of cell in the body — and then into nerve cells.

These cells had a defect in the GBA gene — the most frequent gene risk for Parkinson’s — and their mitochondria. Consequently, their energy production was impaired. Importantly, these cells produced higher levels of damaging oxygen molecules, also known as ROS.

This type of mitochondrial dysfunction and overall damaging response has been associated previously with aging and the decline of an important metabolic compound called NAD+.

No significant changes were observed concerning NAD+ levels in GBA-defective neurons compared to healthy study participants.

However, when researchers analyzed the brains of a fish model of Parkinson’s disease, which also had a mutation in the GBA gene, they found the animals had less nicotinamide mononucleotide, which is the molecule that gives rise to NAD+ compounds.

By feeding GBA-defective neurons with a form of vitamin B3 (called nicotinamide riboside), the levels of available NAD+ were increased and consequently cells’ energy balance improved.

“The nerve cells’ energy budget improved considerably. New mitochondria formed and energy production rose,” Deleidi said.

Treatment with nicotinamide riboside also prevented the loss of motor function in a fly model of Parkinson’s disease. “The substance had a positive effect here as well. In the flies which were treated, far fewer nerve cells died off,” Deleidi added.

Researchers believe that impaired mitochondria play an important role in the development of Parkinson’s and that nicotinamide riboside may represent a potential treatment to overcome this process.

The team is planning to further test the effects of nicotinamide riboside and assess if the vitamin can be of real help for patients with Parkinson’s, as studies have shown this form of vitamin B3 is well-tolerated by healthy subjects and also boosts their energy metabolism.

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Source: Parkinson's News Today