Posts

Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests

BDNF gene mutation

One amino acid change in the brain-derived neurotrophic factor (BDNF) gene, which provides instructions for a protein important to neuronal survival, may be associated with cognitive impairment in Parkinson’s disease patients, a study has found.

The study, “BDNF Val66Met polymorphism and cognitive impairment in Parkinson’s disease—a meta-analysis,” was published in the journal Neurological Sciences.

BDNF protein is produced inside brain cells and is crucial for their function as well as supporting their growth and protecting them against premature cell death. When its coding sequence is changed, this can have a major impact on brain cell outcomes.

Previous studies have suggested that one specific BDNF gene mutation called Val66Met that results in the change of a valine (Val) by a methionine (Met) at position 66 — both amino acids, also known as the protein’s building blocks — could be linked to cognitive impairment in Parkinson’s disease. However, there is no consensus on the relevance of this genetic mutation on outcomes of Parkinson’s patients.

Chinese researchers searched for available literature on this matter, and analyzed pooled data from six studies involving a total of 1,467 patients with Parkinson’s disease. These studies had been carried out in Italy, Spain, Poland, Brazil, Belgrade (Serbia), and the Netherlands.

Results revealed a significant association between the Val66Met BDNF mutation and risk of Parkinson’s disease-related cognitive impairment. Patients who had two copies of the BDNF gene with methionine (mutated version) were found to have a 3.82 times higher risk of developing cognitive impairment than those who had two BDNF copies with valine (non-mutated version).

However, it’s worth mentioning that the studies in this analysis only included Caucasian study samples, so these results should not be generalized to other ethnicities.

Parkinson’s disease affects people of all races and ethnicity worldwide. Some studies indicate that neurodegenerative disorders affect more white people than any other ethnicity, but a solid conclusion cannot be drawn from available research as they tend to vary widely regarding diagnostic criteria, sample sizes, and methodology.

“Future studies should verify our findings in larger populations, particularly in other ethnicities,” the researchers wrote.

Still, the team believes that this study provides evidence that mutated BDNF “may be associated with increased risk of cognitive impairment of Parkinson’s disease, at least among Caucasians.”

In addition, this Val66Met change in the BDNF sequence should be studied in different Parkinson’s patients presenting tremor dominant or postural instability gait disorders. Further understanding of the impact of genetics on the long-term outcomes of these patients “may better guide clinical treatments and judge the prognosis,” they said.

The post Specific BDNF Mutation May Be Linked to Higher Risk of Cognitive Impairment in Parkinson’s, Study Suggests appeared first on Parkinson’s News Today.

Exercise That Motivates Parkinson’s Patients to Push Limits Can Offer Range of Benefits, Experts Say

exercise in Parkinson's

With a treatment not yet within reach that might slow the progression of Parkinson’s disease, much less offer a cure, many — doctors, patients, and researchers alike — are looking to exercise in hopes of fending off a worsening of symptoms.

Interest in exercise-based interventions has risen so much that “the number of publications on exercise studies has increased by a factor of 10 since 2000,” Tanya Simuni, MD, chief of Movement Disorders in the Department of Neurology at Northwestern University, said in a 2016 interview on the International Parkinson and Movement Disorder Society website.

Many consider it common sense that exercise can help to compensate for the motor symptoms that mark Parkinson’s — and research points to this possibility — yet scientists still have few clues as to how exactly it does so.

Work done through the Parkinson’s Outcome Project, an ongoing study involving more than 12,000 patients in five countries, suggests that patients should exercise at least 2.5 hours each week to slow decline and maintain a better quality of life. A similar study advised that patients should begin regular exercise at diagnosis.

Still, this research stops short of recommending a specific exercise regimen as a best strategy.

This has led several enterprises — both for-profit companies and nonprofit groups —  to offer classes ranging from dancing to Parkinson’s-only boxing, and products such as specialized at-home exercise equipment that promise to reduce, reverse, and delay symptoms.

While the literature on exercise in Parkinson’s is “extensive,” Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson’s Disease Association and a practicing neurologist, told Parkinson’s News Today, studies on its effects are typically small. Only recently have they begun to grow in size and in quality — but “translating [their findings] into practical recommendations” is a challenge.

Exercise and the brain

In Parkinson’s, neurons in a brain area called the substantia nigra that are responsible for producing a neurotransmitter called dopamine gradually die off, leading to motor symptoms such as tremor and bradykinesia (slow movement).

Levodopa — which works to increase dopamine levels in the brain but cannot rescue damaged neurons — is currently the front-line treatment for the disease.

Some evidence suggests that, like levodopa, exercise may exert some of its effects by increasing dopamine. A recent study of 17 Parkinson’s patients used positron emission tomography (PET) scans of the brain before and after stationary cycling. Results showed that habitual exercisers in this group — eight patients who exercised more than three hours a week — had higher dopamine levels in the dorsal striatum (the brain area that receives dopamine input from the substantia nigra to help control movement) after stationary cycling than the nine others who were sedentary.

The eight exercisers also performed better on functional tests assessing motor symptoms, including the Unified Parkinson’s Disease Rating Scale (UPDRS) part 3 — which measures items such as gait and time to stand — and in tests of non-motor symptoms such as apathy and depression.

Exercise might also go a step further than levodopa by increasing brain-derived-neurotrophic-factor (BDNF), which promotes the survival of neurons that make dopamine — the same neurons that degenerate in Parkinson’s patients.

An analysis of 12 studies of BDNF levels in Parkinson’s patients found lower levels of BDNF in patients’ serum than in healthy individuals (mean difference of 2.99 ng/mL).

Two of these studies showed that patients who completed exercise programs lasting four, eight, or 12 weeks increased both serum levels of BDNF and UPDRS motor scores.

A separate review of 32 studies related to exercise’s effects on BDNF suggested that aerobic exercise increased BDNF serum levels in healthy people. This was seen to be both an acute effect of a single exercise session and a result of consistent exercise. Strength training did not impact BDNF.

Another Phase 2 study (NCT01506479) divided 128 recently diagnosed patients into three groups that either continued not exercising, participated in 30 minutes of gentle treadmill walking four times a week, or were assigned to six months of high-intensity treadmill exercises for 30 minutes four times a week. Those who did the high-intensity workout maintained the same UPDRS motor score at the study’s end as they had at its start, while those in group that did not exercise saw their scores drop by three points, and those who exercised minimally had a two-point drop.

Rock Steady Boxing

Rock Steady Boxing, a nonprofit, non-combat boxing program designed exclusively for Parkinson’s patients, aims to help all — regardless of skill level — take advantage of the benefits of exercise, while building a supportive and understanding community of patients.

Parkinson’s News Today columnist Jean Mellano, an athlete who not only boxes with Rock Steady but also does physical therapy, yoga, weight training, and daily walking to help treat her Parkinson’s, said “the camaraderie is off the charts.”

Joyce Johnson, Rock Steady’s executive director echoed that sentiment, noting “the magic of Rock Steady is the camaraderie and the fact that all of our boxers are fighting back against same disease.”

Founded in 2006, Rock Steady Boxing has grown in popularity and now operates out of more than 700 locations worldwide.

“We’ve actually had neurologists write Rock Steady Boxing on their little prescription pad and sent them to a location,” Johnson said.

Rock Steady allows affiliates to operate for a small fee in boxing gyms, YMCAs, hospitals, and churches. Some programs are free to patients thanks to grants, but most require participants to pay fees similar to that of an average exercise program.

A typical 90-minute class begins with a warm-up, followed by varied exercises designed to mitigate Parkinson’s symptoms through balance and flexibility work, jumping rope, weightlifting, and, of course, boxing.

A case study, listed on the group’s website and published in the journal Physical Therapyof six Rock Steady boxers showed that after 24-36 classes over the course of 12 weeks, all six boxers improved in at least five out of 12 outcome measures, such as the Functional Reach Test, gait speed, cadence, stride length, step width, and other measures of UPDRS part 3, as well as the Parkinson Disease Quality of Life Scale, an assessment of non-motor symptoms. Patients in earlier disease stages did better at 12 weeks, but those with more advanced disease gained benefits with regular classes that ran for 24 and 36 weeks.

Stephanie Combs-Miller, PhD, the case series’ lead author and an associate professor at the Krannert School of Physical Therapy at the University of Indianapolis, published a slightly larger study in 2013 comparing Rock Steady Boxing with a community-based exercise program that included stretching, resistance, aerobic, and balance-based exercises in 31 patients.

Patients again took part in 24-36 sessions of either workout over the course of 12 weeks. The researchers expected that both programs would lead to improvements, but that the boxers’ improvements would be more dramatic than those of patients in the traditional exercise program.

However, Combs-Miller and her team concluded that “both groups demonstrated significant improvements with the balance, mobility, and quality of life,” supporting the idea that any group-based exercise can help Parkinson’s patients, provided they do it consistently.

Still, as Johnson put it: “How much more fun is that for a grandpa to tell his grandkids that he’s going to boxing instead of saying he’s going to therapy?” 

Theracycle and forced exercise

Rock Steady boxers are encouraged by coaches and peers to attempt moves and workout intensities that seem to push the limits of their abilities.

The Theracycle takes this idea a step further, using a motor that forces patients to pedal the stationary bike faster than they could on their own, theoretically maximizing workout effects.

Jay Alberts, PhD, a biomedical engineer at the Cleveland Clinic and an avid cyclist, went on a 200-mile trip in 2003 on a tandem bike with a friend, who also happened to be a Parkinson’s patient. The friend was forced to pedal at Alberts’ pace, which was about 30 revolutions per minute faster than she would have been able to pedal on her own.  According to Alberts, her tremors disappeared during the ride and for a period of time afterward. 

Alberts brought another patient on his tandem bike and noticed similarly striking results. 

But requiring a strong cyclist to take patients out on tandem bike rides regularly is not a practical treatment plan for 10 million patients worldwide.

The Theracycle, a motorized stationary bicycle based on the exercycle invented in 1932, gives patients a safe way to engage in forced exercise — exercise where, in this case, a motor helps them pedal at a speed they wouldn’t be able to reach on their own — at home without a tandem bike or partner.

Alberts conducted a small study in 2009 at the Cleveland Clinic, which appears on the Theracycle website and was published in the journal Neurorehabilitation and Neural Repair, comparing the effects of forced exercise and voluntary exercise (in which patients choose the intensity at which they exercise) on Parkinson’s symptoms.

Ten patients were randomly assigned to complete three one-hour sessions per week of either voluntary cycling or forced exercise using a motorized cycle. After eight weeks, both groups showed improved aerobic capacity, but only the forced exercise group showed improvements (an average of 35%) on the UPDRS part 3.

Mike Studer, president and co-owner of Northwest Rehabilitation Associates, has been using the Theracycle in his Oregon physical therapy clinic since the company reached out to him more than eight years ago, shortly after the Cleveland Clinic study was published. He said he “remained skeptical” of the new research at first, but that the Theracycle “meets and exceeds” expectations.

His clinic also offers the Rock Steady Boxing program, yoga, treadmills, underwater exercises, and more. Studer says “a repetition is not equal to every other repetition.” With the Theracycle, he can control the intensity of a patient’s workout, a crucial factor in its effectiveness.

The main drawback of the machine is its price. It’s not covered by Medicare, and Rich Blumenthal, chief operating officer of Theracycle, admits that the $3,700-$5,900 price tag (depending on the model) can make the equipment difficult to sell. But patients’ lives “are just better when they start using this,” he says.

Both regimens have one thing in common — pushing patients to do more than they may think they are capable of doing.

“There is nothing wrong with people’s bodies. What’s wrong is that neurologically they quit producing dopamine,” Johnson said.

Whether they are encouraged by coaches or by motors, patients often end up doing more than they ever thought they could.

We may never know which exercise regimen is the most effective for preventing Parkinson’s decline, or which is better for any given patients.

“It’s virtually impossible to imagine testing every single modality versus every other modality,” Gilbert said, but “the answer is it’s probably a little of everything.”

The post Exercise That Motivates Parkinson’s Patients to Push Limits Can Offer Range of Benefits, Experts Say appeared first on Parkinson’s News Today.

Exercise Can Raise BDNF Levels, Alleviate Depression in Parkinson’s Patients, Review Shows

BDNF levels

Levels of brain-derived neurotrophic factor (BDNF) — a protein important in promoting the survival of dopaminergic neurons — are abnormally low in patients with Parkinson’s disease, regardless of whether these patients also have depression, a common non-motor symptom associated with the disease, a systematic review study reveals.

The study also revealed that exercise can increase BDNF levels in Parkinson’s patients, highlighting exercise’s potential not only to treat depression, but also motor symptoms typically associated with Parkinson’s disease.

The systematic review, “Plasma levels of brain-derived neurotrophic factor in patients with Parkinson disease: A systematic review and meta-analysis,” was published in Brain Research.

BDNF is an abundant protein whose main function is to protect dopaminergic neurons located in the substantia nigra — a region of the brain responsible for movement control — that are gradually lost in the course of Parkinson’s disease.

Although no literature consensus exists, some studies have shown that blood serum BDNF levels decrease in patients with depression and increase after intense exercise in healthy adults.

In this systematic review, the authors focused on gathering and discussing data from previous studies assessing blood serum levels of BDNF in Parkinson’s patients.

After a thorough screening in three different databases (MEDLINE, EMBASE and SCOPUS), 12 eligible studies were selected, including five comparing serum BDNF levels of Parkinson’s patients to those of healthy control subjects and three comparing serum BDNF levels of depressed and non-depressed Parkinson’s patients.

Data revealed that Parkinson’s patients tend to have lower levels of BDNF in their serum, compared to healthy control individuals (mean difference of 2.99 ng/mL). Parkinson’s patients who also had depression had even lower levels of BDNF compared to healthy control subjects (mean difference of 4.83 ng/mL).

No differences in BDNF levels were found between depressed and non-depressed Parkinson’s patients.

There was also a positive correlation between serum BDNF levels and patients’ male gender, disease duration and Hoehn and Yahr motor score — a commonly used system to describe the progression of Parkinson’s symptoms.

There is “a direct relationship between [Parkinson’s disease] progression and worsening of motor symptoms and higher serum BDNF. We believe that this could be a result of a compensatory mechanism in response to progressive loss of dopaminergic neurons of the substantia nigra and progressive [reduction] of neurotrophin expression in the remaining neurons. This could also reflect a possible effect of medications, namely antidepressants and dopamine replacement therapy,” researchers said.

Four studies also analyzed the effects of exercise on serum BDNF levels, while two others focused on the relationship between Parkinson’s disease severity and patients’ physical capacity and serum BDNF levels.

While there was no relationship between patients’ physical capacity and serum BDNF levels, a significant increase in BDNF levels was seen in patients with mild to moderate Parkinson’s after four or eight weeks of physical training, which was accompanied by an improvement of UPDRS motor scores and patients’ performance on the 6-minute walking test, used to assess aerobic capacity and endurance.

Another study reported similar findings in depressed Parkinson’s patients who participated in a 12-week exercise program.

“Our results proved that PD is of equal potential to [decrease] BDNF expression as depression, which is a common co-morbid condition in PD. The potential for exercise to induce BDNF expression in PD patients justifies that physical training might prove useful to treat depressive symptoms as well as motor complications of PD patients,” researchers concluded.

The post Exercise Can Raise BDNF Levels, Alleviate Depression in Parkinson’s Patients, Review Shows appeared first on Parkinson’s News Today.

Genervon Presents Future Goals for Investigational GM6 Therapy in Parkinson’s, Other Diseases

genervon

Genervon Biopharmaceuticals announced its future goals for investigational therapy GM6 in a recent presentation on its multi-target drug development strategy to tackle neurodegenerative diseases, including Parkinson’s disease.

Genervon presented its hypothesis that a multi-target drug approach is the key to curing complex neurological disorders at the 2018 BIO CEO & Investor Conference on Feb. 12, 2018, at the New York Marriott Marquis.

Following this strategy, researchers at Genervon previously discovered what they believe is the regulator of the development of the human nervous system, called the motoneuronotrophic factor (MNTF).

The company then developed GM6, a synthetic equivalent of MNTF, and launched a comprehensive clinical program to test GM6 as a potential treatment for Parkinson’s disease and other central nervous system (CNS) diseases.

Phase 2 trials are now being planned to test GM6 in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis.

MNTF is an endogenous neurotrophin — a growth factor that induces the survival, development, and function of neurons — highly specific of the central nervous system and expressed rapidly during the first three months of human embryonic development of the complete nervous system, peaking at week nine and remaining detectable in adult tissue.

Previous studies showed that MNTF regulates embryonic stem cell differentiation into motor neurons and helps maintain these nerve cells. Additionally, MNTF helps motor axon regeneration and restoration of nerve function in target muscles and organs.

GM6 controls the development, monitoring, and correction of the human nervous system. It can traverse the blood-brain barrier — a highly selective membrane that helps shield the brain and central nervous system from blood circulation — and activate an embryonic program to help detect and repair damages to the central nervous system, including those triggered in Parkinson’s and other neurodegenerative diseases.

Genervon’s pre-clinical studies identified six potential mechanisms of action of GM6 in Parkinson’s disease, including the down-regulation or up-regulation of six genes involved in signalling, growth factor generation, or oxidative stress defense.

In 2013, Genervon launched a Phase 2a clinical trial (NCT01850381) to assess GM6’s safety and tolerability in Parkinson’s disease patients.

The pilot study enrolled six patients, who were randomized to receive either intravenous GM6 and a placebo. They received six doses of GM6 or placebo over two weeks. Researchers measured the levels of brain-derived neurotrophic factor (BDNF), a blood marker for Parkinson’s disease, at the start (visit one), after four doses (visit four), after six doses (visit six) and 10 weeks post-treatment (visit eight).

Changes in BDNF blood levels for each patient relative to baseline were analyzed at visits four, six, and eight. The results showed that GM6 was well-tolerated and linked to favorable changes in BDNF.

GM6 has also been granted orphan drug status and a fast-track designation by the U.S. Food and Drug Administration to treat amyotrophic lateral sclerosis (ALS), and a Phase 3 trial is being planned to test GM6 in ALS.

The post Genervon Presents Future Goals for Investigational GM6 Therapy in Parkinson’s, Other Diseases appeared first on Parkinson’s News Today.

Source: Parkinson's News Today