Posts

New Therapy Using Patients’ Own Cells May Halt Parkinson’s Progression, Case Study Suggests

transplanting cells

A new therapeutic approach in which patient-derived dopamine-producing neurons are transplanted into the brain may halt Parkinson’s disease progression, a case report suggests.

The approach uses patient-derived induced pluripotent stem cells (iPSCs),  which are cells collected from the skin or blood that researchers can reprogram in a lab dish to revert them back to a stem cell-like state that has the capacity to then differentiate into almost any cell type.

“Because the cells come from the patient, they are readily available and can be reprogrammed in such a way that they are not rejected on implantation. This represents a milestone in ‘personalized medicine’ for Parkinson’s,” Kwang-Soo Kim, PhD, said in a news story. Kim is co-senior author of the study and director of the Molecular Neurobiology Laboratory at McLean Hospital in Massachusetts.

Two-year data following the first of two interventions suggest the therapy resulted in at least a stabilization of the patient’s motor function and an improved quality of life. However, clinical studies with longer follow-up periods are needed to confirm the therapeutic potential of this approach in Parkinson’s patients, the researchers noted.

The case study, “Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease,” was published in the New England Journal of Medicine.

Parkinson’s is characterized by the gradual loss of dopamine-producing (dopaminergic) neurons in the substantia nigra, a region of the brain responsible for movement control. The death of dopaminergic neuron results in lower dopamine levels, affecting the regulation of muscle movement and coordination.

While the potential use of tissue transplants to replace the lost dopaminergic neurons in Parkinson’s patients has been studied since the 1980s, the creation of iPSCs offered the hope to transplant precursors of dopaminergic neurons into a patient’s brain.

In 2018, a team of researchers in Japan reported the implantation of precursors of dopaminergic neurons into the brain of a Parkinson’s patient. Six other patients were expected to receive this experimental therapy that used iPSCs developed from skin cells of an anonymous donor. Researchers plan to collect all safety and effectiveness data by the end of this year.

When implanting cells derived from other individuals, patients need to receive immunosuppressive therapies (for an undetermined period of time) to prevent the development of immune responses against the implanted cells. However, the use of a patient’s own cells would make the need for immunosuppression unnecessary.

Now, a team of researchers at the McLean Hospital and Massachusetts General Hospital (MGH) reported the case of a 69-year-old man treated with a similar approach using the patient’s own iPSCs.

The man had a 10-year history of progressive Parkinson’s disease with no signs of dyskinesia (abnormal involuntary movements that characterize advanced Parkinson’s). He was treated with extended release carbidopalevodopa tablets, Neupro patches (by UCB), and Azilect (by Teva Pharmaceuticals).

He reported poor control of his symptoms, with three hours of “off”-periods — when the medications’ effects wear off and symptoms worsen before a new dose can be taken. Higher levodopa doses caused him lightheadedness associated with a drop in blood pressure when changing to a standing position (orthostatic hypotension).

The researchers used the man’s skin cells to create iPSCs and develop them into precursors of dopaminergic neurons, which were tested extensively, including a mouse model used in human-derived transplant studies.

Using these data, Kim applied to the U.S. Food and Drug Administration (FDA) for a single-patient, investigational new drug application and also received approval from the hospital board to implant the cells into the patient’s brain.

The man underwent two surgeries, in 2017 and 2018 (separated by six months) at the Weill Cornell Medical Center in New York, and at MGH.

At each surgery, four million cells were delivered into the putamen, a large brain structure involved in movement control that is filled with dopamine receptors and receives signals from the substantia nigra. The first intervention targeted the putamen on the left hemisphere of the brain, while the second targeted the one on the right hemisphere.

The cells were delivered using a new minimally invasive neurosurgical implantation procedure developed by Jeffrey Schweitzer, MD, PhD, the study’s lead author, a Parkinson’s specialized neurosurgeon, in collaboration with other neurosurgeons at MGH and Weill Cornell. Schweitzer is director of the Neurosurgical Neurodegenerative Cell Therapy program at MGH.

The patient’s motor function was assessed through the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and quality of life with the 39-item Parkinson’s Questionnaire.

Two years after the first intervention, imaging tests showed that the transplanted cells were alive and working correctly as dopaminergic neurons, highlighting the technical success of this personalized cell-replacement approach.

There were no reports of side effects or immune reactions against the cells (without the need for immunosuppressive therapy), or signs that the cells caused any unwanted growth or tumors.

Notably, there was at least a stabilization in the man’s motor function, with MDS-UPDRS scores varying over time, but never reaching the initial values, and he reported improvements in his day-to-day activities and quality of life.

The man reported less than one hour of “off” period per day and the levodopa equivalent daily dose was lowered by 6%, “a reduction of uncertain clinical importance,” the researchers wrote.

“This strategy highlights the emerging power of using one’s own cells to try and reverse a condition — Parkinson’s disease — that has been very challenging to treat. I am very pleased by the extensive collaboration across multiple institutions, scientists, physicians, and surgeons that came together to make this a possibility,” said Bob Carter, MD, PhD, another co-senior author of the study and MGH’s chief of Neurosurgery.

Despite these apparently positive results, the researchers emphasized this is just a first step in this therapy’s development.

“These results reflect the experience of one individual patient and a formal clinical trial will be required to determine if the therapy is effective,” said Schweitzer.

The post New Therapy Using Patients’ Own Cells May Halt Parkinson’s Progression, Case Study Suggests appeared first on Parkinson’s News Today.

Case Report Describes Secondary Parkinsonism Due to Cavernoma in the Striatum

secondary parkinsonism

Secondary parkinsonism can be caused by a cavernoma — a cluster of abnormal blood vessels — located in a brain region involved in voluntary movement control, a case report shows.

The case-study, ”Nine-years follow-up of cavernoma located in basal ganglia mimicking Parkinson’s disease,” was published in the journal Clinical Neurology and Neurosurgery.

Most patients (about 80–85%) diagnosed with Parkinson’s disease have what is called primary parkinsonism or idiopathic Parkinson’s disease (meaning the disease has no known cause). This type tends to respond well to therapies that work by increasing or substituting dopamine molecules in the brain.

The remaining types of Parkinson’s are known as secondary parkinsonism. In these cases, the cause of the disease is often known, but patients fail to respond well to dopaminergic medications intended to replace dopamine or prevent its degradation, such as levodopa.

Secondary parkinsonism can be caused by a variety of factors. In rare cases, it is caused by cavernoma, a cluster of abnormal blood vessels in the basal ganglia (a brain region often affected in Parkinson’s). This occurs in only 0.46% of the general older population, and in 0.037% of  older individuals with Parkinson’s symptoms, according to the report.

In this study, researchers cite the case of a 75-year-old woman with secondary parkinsonism due to a cavernoma in the right striatum — a brain region involved in voluntary movement control — and one of the major components of the basal ganglia.

In 2009, the patient was diagnosed with Parkinson’s after clinical examination by a neurologist. Her symptoms included bradykinesia (slowness of movement) and rigidity of her left limbs, cogwheel phenomenon (a type of rigidity common in Parkinson’s) of the right upper-limb that occured upon contralateral (opposite) hand activation, and an unsteady gait.

“The patient referred to a loss of interest in her hobbies in the preceding years and difficulties in initiating speech and movement,” the researchers wrote.

The neurologist, suspecting Parkinson’s disease, recommended brain magnetic resonance imaging (MRI), a Dopamine Transporter Single Photon Emission Computerized Tomography (DaTscan), and an olfactory (smell) test.

DaTscan is a tool used to confirm the diagnosis of Parkinson’s disease. It is a specific type of single-photon emission computed tomography (SPECT) imaging technique that helps visualize dopamine transporter levels in the brain. In Parkinson’s, there is a steady loss of dopamine transporters (DaT) in the brain. These mediate the flow of the neurotransmitter dopamine between nerve cells.

The results revealed severely decreased dopamine transporter uptake in the right striatum. The brain MRI scan showed that the patient had a 2-centimeter cavernoma in the basal ganglia, as well as small vessel disease (microangiopathy), which also was detected in the brain’s white matter.

The olfactory test showed no impairment in her ability to smell or to detect odors (a condition called hyposmia).

As a result, the patient, who never had received medication that could have caused secondary parkinsonism, was given low-dose levodopa.

Over a nine-year period, however, her left kimb parkinsonism did not appear to progress. The patient never experienced rest tremor, motor fluctuations or dyskinesia (involuntary muscle movement) typical of Parkinson’s. Only the patient’s apathy and gait unsteadiness appeared to deteriorate. Furthermore, the patient stated that she did not respond to levodopa treatment, even following a dose increase to 750 mg/day.

As a result, neurologists re-evaluated her diagnosis. They performed the levodopa test and the apomorphin-challenge-test, both used to determine whether motor symptoms such as tremors in the limbs, rigidity in the muscles, and problems with walking, balance and fine motor coordination, are caused by Parkinson’s.

The tests consist of giving levopoda or apomorphine (brand name Apokyn) to understand if these Parkinson’s-specific treatments improve patients’ symptoms. If it does, the patient likely has Parkinson’s.

The results for both tests were negative. Brain MRI showed that the cavernoma had increased slightly in size. Another DaTscan showed that the dopamine transporter uptake had undergone a mild-to-moderate worsening compared to the first assessment.

One week after progressively discontinuing levopoda treatment altogether, the patient showed no worsening of her symptoms.

Based on all these observations, the patient was diagnosed with secondary parkinsonism caused by cavernoma. “We conclude that a cavernoma in the striatum can cause secondary parkinsonism and apathy mimicking PD at the first neurological assessment,” the researchers wrote.

Unlike Parkinson’s, secondary parkinsonism caused by cavernoma can remain unchanged over many years, and lead to the drop of dopamine receptors detected in the DaTscan.

The post Case Report Describes Secondary Parkinsonism Due to Cavernoma in the Striatum appeared first on Parkinson’s News Today.

Deep Brain Stimulation May Impair Swimming Ability and Increase Risk of Drowning, Case Studies Suggest

swim DBS

Patients who undergo deep brain stimulation to treat Parkinson’s disease may lose their ability to swim, even if their motor symptoms improve after the treatment or if they were formerly proficient swimmers, a collection of nine case studies has found.

The study, “Beware of deep water after subthalamic deep brain stimulation,” was published in the journal Neurology.

“Until more research is done to determine why some people with deep brain stimulation can no longer swim, it is crucial that people be told now of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water,” Daniel Waldvogel, MD, researcher at the University of Zurich in Switzerland and lead author of the study, said in a press release.

Deep-brain stimulation (DBS) is an invasive surgical treatment in which fine wires are inserted into the brain and connected to a device placed under the skin in the upper chest. The device controls electrical impulses to stimulates areas responsible for movement control, such as the subthalamic nucleus.

DBS is usually used on Parkinson’s patients whose motor symptoms do not respond well to standard medications, and studies have shown long-term improvements in motor symptoms, quality of life, ability to perform regular daily activities, and a significant reduction in the need for levodopa.

However, researchers now say that despite a successful surgical procedure and improvement in motor symptoms, some patients can lose their ability to swim.

The nine patients described in the study had received deep brain stimulation of the subthalamic nucleus, and all were highly satisfied with the treatment’s overall outcome. “However, they were frustrated by their lost ability to coordinate limb movements for swimming,” the researchers said.

The researchers described three of the nine cases in their study.

The first case was a 69-year-old man who lived by a lake and was an experienced and proficient swimmer. Due to his good motor outcomes after undergoing DBS, the man was confident enough to jump into the lake, but he would have drowned if not rescued by a family member.

The second case was of a woman, 59, who was a competitive swimmer and continued to swim even after being diagnosed with Parkinson’s. However, after undergoing DBS, she lost her ability to swim, which never came close to her previous level even after regular swimming practice with a physical therapist.

Finally, researchers reported the case of a 61-year-old woman with a lifesaving diploma, who used to swim in competitions crossing Lake Zurich, which is two miles wide. After the surgical procedure, however, she could barely swim two-tenths of a mile and complained of an awkward posture when trying to swim.

“Swimming is a highly coordinated movement that requires complicated arm and leg coordination,” Waldvogel said. “Exactly how deep brain stimulation is interfering with this ability needs to be determined.”

Three of the nine patients turned off their DBS devices and immediately regained their ability to swim. However, this led to worsening of their other motor symptoms, which made them switch on their devices again.

“Even though these reports affected only a few people, we felt this potential risk was serious enough to alert others with Parkinson’s disease, as well as their families and doctors,” Waldvogel said.

More studies are warranted to better understand the real adverse effects of DBS, including its impact on patients’ ability to swim.

The post Deep Brain Stimulation May Impair Swimming Ability and Increase Risk of Drowning, Case Studies Suggest appeared first on Parkinson’s News Today.

Report Showcases Benefits of Creativity Induced by Levodopa

Levodopa

A new report describes two Indian men with Parkinson’s disease who experienced “creative awakenings” after they started being treated with levodopa.

Appropriately titled, “A tale of two patients: Levodopa and creative awakening in Parkinson’s disease – A qualitative report,” the study was published in the Asian Journal of Psychiatry.

Levodopa is one of the mainstays of Parkinson’s treatment, and there have been scattered reports of people treated with it developing increased artistic creativity. The new study details the cases of two men, both from India, where levodopa-induced creativity has not been previously reported.

The first man, Mr. A, is a 68-year-old shopkeeper. He developed symptoms of Parkinson’s in 2010, and began treatment with levodopa in 2017.

Six months after he started on levodopa, Mr. A noticed some coconut shells lying in his yard and was struck by the urge to make something out of them. “It just happened, I just had these ideas,” he is quoted in the study as saying.

Mr. A began making various things out of the coconuts — pen holders, paperweights, cups, and more. He kept doing it, and now makes five to 10 such items per day.

Although he claims he was “not an artistic kind of person before all this,” Mr. A now sells his crafts at various shops. Although it’s not a full-fledged business, he says it does help him with his finances.

The second man, Mr. R, is a 63-year-old farmer who was diagnosed with Parkinson’s in 2011. He began levodopa treatment in 2015, and shortly thereafter, upon seeing his grandchild coloring, decided to start painting.

“I draw or paint all the time. I just can’t stop,” he said. “I’ve been doing it for nearly three years now.”

Mr. R, who regularly paints two or three pictures a day, has turned this newfound passion into a career. “Now it is a major source of income for me,” he said. “What gives me greater happiness is that I use the money I generate to support other people who need financial assistance for their medical needs.”

Both Mr. A and Mr. R are, on the whole, quite satisfied with the unexpected turns their lives have taken.

“I feel it’s given me a purpose in life,” said Mr. R. “If Parkinson’s disease was the only way I could have done all this, I won’t complain, honestly.”

“‘I am really happy. I don’t know what else to say,” said Mr. A.

It’s not clear exactly why levodopa treatment leads to creative awakenings in some patients. Several mechanisms have been proposed, such as:

  • “Creativity is a result of hyperactivity and behavioral disinhibition;”
  • “Creativity is a result of stimulation by dopamine agonists;”
  • “Creativity might be the emergence of innate skills in some predisposed Parkinson’s patients on dopaminergic therapy.”

However, in this report, researchers wanted to emphasize how this creative expression could be beneficial to patients.

“All in all, it would seem reasonable to assume that [making art] helped [Mr. A and Mr. R] cope positively with [Parkinson’s] and its deficits,” the researchers said. “Such artistic expression is therapeutic; it’s a form of art therapy, and we call for this usefulness to be further explored in routine clinical practice.”

The post Report Showcases Benefits of Creativity Induced by Levodopa appeared first on Parkinson’s News Today.

Encephalitis Symptoms Masked as Worsening Parkinson’s Disease, Case Report Shows

encephalitis case report

Parkinson’s disease can sometimes mask the symptoms of other neurological disorders, according to a case report.

The report, titled “NMDAR encephalitis presenting as akinesia in a patient with Parkinson disease,” documents the case of a 71-year-old woman who was eventually diagnosed with encephalitis, the symptoms of which were first thought to be caused by a worsening of her Parkinson’s.

It was published in the Journal of Neuroimmunology.

The patient, who had a two-year history of Parkinson’s, had initially experienced some difficulty moving her left arm, a condition called bradykinesia, but was generally responding well to levodopa, a mainstay of Parkinson’s treatment.

Then, at the end of 2017, her symptoms started to worsen. Her bradykinesia increased to the point that she was unable to move her arm at all, defined as akinesia. In April 2018, she was admitted to a hospital due to difficulty moving and swallowing.

She stopped responding to levodopa treatment, and her condition continued to decline. She eventually became unresponsive; the authors described her state as being nearly catatonic.

Because the disease was continuing to progress and wasn’t responding to treatment, the doctors decided to examine her cerebrospinal fluid, the liquid that surrounds the brain and spinal cord.

After taking a sample of the patient’s cerebrospinal fluid and running a series of tests, they found antibodies against N-methyl-D-aspartate receptor (NMDAR). These antibodies are a hallmark of encephalitis, which occurs when there is inflammation in the brain — essentially, the body’s immune system attacks cells in or near the nervous system, which is not conducive to proper neurological function.

Typically, encephalitis presents as a severe disease with rapidly worsening symptoms. In this particular case, this was still true — but because the patient had Parkinson’s, which shares some similar symptoms, she was believed to be experiencing worsening Parkinson’s, and not an altogether separate disease.

“Our case should alert neurologists that NMDAR-E [encephalitis associated with antibodies against NMDAR] onset in PD [Parkinson’s] patients could manifest mainly as worsening of PD,” the researchers wrote.

After the correct diagnosis was made, appropriate treatment was swiftly given, and the patient responded well. She gradually regained her function and had completely recovered within three months, her symptoms returning to just bradykinesia of her left arm.

As is often the case in acute encephalitis, the patient has no memory of what occurred during the worst parts of the disease.

The post Encephalitis Symptoms Masked as Worsening Parkinson’s Disease, Case Report Shows appeared first on Parkinson’s News Today.

Man-made Cannabis Induced Psychosis in Parkinson’s Patient, Case Report Says

Cannabis and psychosis

A recent case report describes a 70-year-old woman with Parkinson’s disease who developed psychosis after taking nabilone, a man-made form of cannabis often used to treat severe nausea caused by cancer chemotherapy.

The study, “Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old woman with Parkinson disease,” was published in the Canadian Medical Association Journal (CMAJ).

Psychosis, although not fully understood, is common in Parkinson’s disease, particularly in its later stages. Symptoms include minor illusions, vivid dreams, occasional visual hallucinations with loss of insight, paranoia and panic attacks. More than half of all Parkinson’s patients eventually develop some kind of non-motor symptoms over the course of their disease.

There’s no predicting with certainty which Parkinson’s patients will go on to develop symptoms like hallucinations or delusions. Several risk factors are associated with the disorder, including age, duration and severity of Parkinson’s disease and dopamine therapy.

There’s no reliable evidence to support cannabinoid use as a management therapy for Parkinson’s symptoms and some studies suggest cannabis may trigger or worsen psychosis even in the absence of a psychiatric history. However, when desperate for symptom relief, some patients may use medical marijuana and cannabinoids.

Canadian clinicians reported the case of the woman, diagnosed with Parkinson’s for more than 12 years, who complained of chronic, painful, involuntary and repetitive twisting, plus sustained muscle contractions (dystonia). The patient also was resistant to multiple Parkinson’s drugs.

Her family doctor prescribed nabilone to relieve symptoms. “The patient took two doses (1 mg) that resulted in intrusive visual hallucinations, panic and paranoia within hours. Despite stopping treatment with nabilone after the two doses, the patient’s psychosis worsened over the next three weeks. She had delusions that her neighbors were engaged in illegal and dangerous activities,” the team reported.

Before nabilone’s ingestion, the patient had occasional visual hallucinations for years and mild cognitive impairment, but she was able to independently lead her daily life at home.

No changes were made to her medication — levodopa/carbidopa (1,000/250 mg per day), entacapone (1,000 mg per day), pramipexole (4.5 mg per day) and amantadine (300 mg per day) — prior to the onset of non-motor symptoms.

Three-weeks after nabilone, cognitive assessment revealed the patient’s orientation, attention, delayed recall and abstraction deteriorated, in comparison to her cognitive state prior to taking nabilone.

Even though doctors adjusted her medication after psychosis occurred, her symptoms worsened, and two months after ingesting nabilone the patient was admitted to the hospital.

After a few weeks and several medication adjustments, the patient’s psychosis subsided, and she was discharged with a new drug protocol, which included levodopa/carbidopa (1,000/250 mg/d), entacapone (1,000 mg/d), controlled-release levodopa/carbidopa (100/25 mg/d), fludrocortisone (0.1 mg in the morning) and clozapine (37.5 mg at bedtime).

While not so severe, the patient’s visual hallucinations and delusions were still occurring three months after discharge.

“Although the patient’s Parkinson disease, anti-parkinsonian drugs and previous psychiatric symptoms may have provided a predisposition to the development of psychosis, ingestion of nabilone was the clear trigger that caused her psychotic symptoms to become established and then spiral out of control,” the authors wrote.

Given the observed effects of cannabinoid use in a susceptible Parkinson patient, clinicians have developed a patient information sheet to alert for cannabinoids’ potential side effects in Parkinson’s disease.

The post Man-made Cannabis Induced Psychosis in Parkinson’s Patient, Case Report Says appeared first on Parkinson’s News Today.

Source: Parkinson's News Today